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Novedades en el tratamiento del Hiperparatiroidismo
secundario (HPS) Barcelona 22 Marzo 2018
Mordf Jesuacutes Lloret Fundacioacute Puigvert Barcelona
AGENDA 1 Fisiopatologia 2 PTH targets 3 Tratamientos antiparatiroideosvitamina D
activa 4 Tratamientos antiparatiroideos calcimimeacuteticos 5 Conclusiones
FISIOPATOLOGIA Hiperparatiroidismo secundario
Adaptado de MRodriguez amp ME Rodriacuteguez Ortiz Expert Opin Pharmacother 2015 Isakova et al KI 2011
Ca-R (-) VD-R (-)
P-R (+)
FGF23Klotho(-)
FISIOPATOLOGIA Hiperparatiroidismo secundario
Wei Ling Lau Yoshitsugu Obi and Kamyar Kalantar-Zadeh Clin J Am Soc Nephrol 2018
FISIOPATOLOGIA Hiperparatiroidismo secundario
Basile C adn Carlo Lomonte Kidney International 92 1046-1048 2017
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
FISIOPATOLOGIA PTH como ldquotoxina ureacutemicardquo
H Komaba T Kakuta M Fkagawa Clin Exp Nephrol 21S37-S45 2017
1 NKF KDOQI Am J Kidney Dis 200342(suppl 3)S1-S202) 2 KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
4 Torregrosa J-V et al Nefrologia 201131(Suppl 1)3ndash32 5Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
GUIAS PRAacuteCTICA CLINICA Target PTH
KDOQI 20031
KDIGO 20092
SEN 20114
KDIGO 20175
P 13ndash178 mmolL
(35-55 mgdl) ldquoTowardsrdquo
normal Normal
Long gap Tolerance up to 16
mmolL (5 mgdl)
ldquoTowardsrdquo normal
(including 3a-5D)
Ca Normal preferably towards the lower
end (21ndash237 mmolL)
Normal Normal Avoiding hypercalcemia
iPTH 150ndash300 ngL 2ndash9 times the upper normal range of the
assay
150ndash300 pgmL Evitar lt100 gt500 PTH
conversor (2ndash5 veces el liacutemite
superior de la normalidad para el ensayo usado)
2ndash9 times the upper normal range of the
assay
HUESO SUPERVIVENCIA
Floege J et al Nephrol Dial Transplant doi101093ndtgfq219
TARGET PTH Mortality Risk
Patients with iPTH calcium and phosphate levels within the KDOQI target ranges have the LOWEST RISK OF MORTALITY compared with those outside the target ranges
SEN 2011 5D iPTH 150-300 pgml No emergency and trends
MJ Prados-Garrido et al Dial Transpl 2011
Dialysis population (Fresenius Europe)
Recent changes in therapeutic approaches and association with outcomes among patients with SHPT on
chronic hemodialysis the DOPPS study Clin J Am Soc Nephrol 2015 Jan 710(1)98-109 Tentori F et al
RESULTS
Median parathyroid hormone increased from phase 1 to phase 4 in all regions except for Japan where it remained stable Prescriptions of intravenous vitamin D analogs and cinacalcet increased and parathyroidectomy rates decreased in all regions over time Compared with 150-300 pgml in adjusted models all-cause mortality risk was higher for parathyroid hormone=301-450 (hazard ratio 109 95 confidence interval 101 to 118) and gt600 pgml (hazard ratio 123 95 confidence interval 112 to 134) Parathyroid hormone gt600 pgml was also associated with higher risk of cardiovascular mortality as well as all-cause and cardiovascular hospitalizations In a subgroup analysis of 5387 patients not receiving vitamin D analogs or cinacalcet and with no prior parathyroidectomy very low parathyroid hormone (lt50 pgml) was associated with mortality (hazard ratio 125 95 confidence interval 104 to 151)
CONCLUSIONS
In a large international sample of patients on hemodialysis parathyroid hormone levels increased in most countries and secondary hyperparathyroidism treatments changed over time Very low and very high parathyroid hormone levels were associated with adverse outcomes In the absence of definitive evidence in support of a specific parathyroid hormone target
there is an urgent need for additional research to inform clinical practice
TARGET PTH Fenotipos CKD-MBD Ca P HIGH
Ca P normal
Block G et al Clin J Am Soc Nephrol 82131-21402013
PTH 150-300 + Ca N + P N (20)
PTH gt600+ Ca N + P uarr (11) PTH 301-600+ Ca N + P uarr (16) PTH 301-600+ Ca N + P N (15)
PTH
P
P
P
P P
QUELANTES DEL P + ANTIPARATIROIDEOS
GUIAS PRAacuteCTICA CLINICA Ca P PTH valoracioacuten conjunta
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015 CM No predialysis Tolerance N ampV hypocalcemia (QT) seizures risk
TRATAMIENTOS ANTIPARATIROIDEOS
Improved survival in dialysis patients with oral vit D (967 calcitriol) in South America (n = 16004) (CORES)
Naves-Diacuteaz M et al Kidney Int 2008
bull OVERALL CARDIOVASCULAR INFECTIOUS and NEOPLASTIC mortality improved bull Unadjusted mortality rates (white bars)
bull Adjusted mortality (grey bars)
VITAMINA D ACTIVA
VITAMINA D ACTIVA Survival in HD Comparation between Paricalcitol and Calcitriol
Teng M et al N Engl J Med 2003349446ndash56
0 5 10 15 20 25 30 35 40
Paricalcitol Calcitriol
Surv
ival
()
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25 30 35 40
Surv
ival
()
Switch to calcitriol
0
10
20
30
40
50
60
70
80
90 100
Switch to paricalcitol
3-year survival 59 vs 51 Log rank plt0001
2-year survival 73 vs 64 Log rank p=004
n=67399 n=16483
Follow-up (months)
NOVEDADES TRATAMIENTO VITAMINA D Inhibidores CYP24
Calcitriol
1-α-Hidroxilasa
Guillaume Jean et Al Nephro and Ther 2009
bull CTAP 101 calcifediol de liberacioacuten retardada
bull Inhibidores CYP24
Bover J et al Expert Opinion on Pharmacotherapy 2016
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015
TRATAMIENTOS ANTIPARATIROIDEOS
MECANISMO DE ACCIOacuteN CALCIMIMEacuteTICO
Goodman WG et al Adv Renal Replace Therapy 200292000ndash8 Nemeth EF et al Proc Natl Acad Sci USA 1998954040ndash5
Serum Ca2+ Serum Ca2+ Serum Ca2+
+ cinacalcet
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
AGENDA 1 Fisiopatologia 2 PTH targets 3 Tratamientos antiparatiroideosvitamina D
activa 4 Tratamientos antiparatiroideos calcimimeacuteticos 5 Conclusiones
FISIOPATOLOGIA Hiperparatiroidismo secundario
Adaptado de MRodriguez amp ME Rodriacuteguez Ortiz Expert Opin Pharmacother 2015 Isakova et al KI 2011
Ca-R (-) VD-R (-)
P-R (+)
FGF23Klotho(-)
FISIOPATOLOGIA Hiperparatiroidismo secundario
Wei Ling Lau Yoshitsugu Obi and Kamyar Kalantar-Zadeh Clin J Am Soc Nephrol 2018
FISIOPATOLOGIA Hiperparatiroidismo secundario
Basile C adn Carlo Lomonte Kidney International 92 1046-1048 2017
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
FISIOPATOLOGIA PTH como ldquotoxina ureacutemicardquo
H Komaba T Kakuta M Fkagawa Clin Exp Nephrol 21S37-S45 2017
1 NKF KDOQI Am J Kidney Dis 200342(suppl 3)S1-S202) 2 KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
4 Torregrosa J-V et al Nefrologia 201131(Suppl 1)3ndash32 5Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
GUIAS PRAacuteCTICA CLINICA Target PTH
KDOQI 20031
KDIGO 20092
SEN 20114
KDIGO 20175
P 13ndash178 mmolL
(35-55 mgdl) ldquoTowardsrdquo
normal Normal
Long gap Tolerance up to 16
mmolL (5 mgdl)
ldquoTowardsrdquo normal
(including 3a-5D)
Ca Normal preferably towards the lower
end (21ndash237 mmolL)
Normal Normal Avoiding hypercalcemia
iPTH 150ndash300 ngL 2ndash9 times the upper normal range of the
assay
150ndash300 pgmL Evitar lt100 gt500 PTH
conversor (2ndash5 veces el liacutemite
superior de la normalidad para el ensayo usado)
2ndash9 times the upper normal range of the
assay
HUESO SUPERVIVENCIA
Floege J et al Nephrol Dial Transplant doi101093ndtgfq219
TARGET PTH Mortality Risk
Patients with iPTH calcium and phosphate levels within the KDOQI target ranges have the LOWEST RISK OF MORTALITY compared with those outside the target ranges
SEN 2011 5D iPTH 150-300 pgml No emergency and trends
MJ Prados-Garrido et al Dial Transpl 2011
Dialysis population (Fresenius Europe)
Recent changes in therapeutic approaches and association with outcomes among patients with SHPT on
chronic hemodialysis the DOPPS study Clin J Am Soc Nephrol 2015 Jan 710(1)98-109 Tentori F et al
RESULTS
Median parathyroid hormone increased from phase 1 to phase 4 in all regions except for Japan where it remained stable Prescriptions of intravenous vitamin D analogs and cinacalcet increased and parathyroidectomy rates decreased in all regions over time Compared with 150-300 pgml in adjusted models all-cause mortality risk was higher for parathyroid hormone=301-450 (hazard ratio 109 95 confidence interval 101 to 118) and gt600 pgml (hazard ratio 123 95 confidence interval 112 to 134) Parathyroid hormone gt600 pgml was also associated with higher risk of cardiovascular mortality as well as all-cause and cardiovascular hospitalizations In a subgroup analysis of 5387 patients not receiving vitamin D analogs or cinacalcet and with no prior parathyroidectomy very low parathyroid hormone (lt50 pgml) was associated with mortality (hazard ratio 125 95 confidence interval 104 to 151)
CONCLUSIONS
In a large international sample of patients on hemodialysis parathyroid hormone levels increased in most countries and secondary hyperparathyroidism treatments changed over time Very low and very high parathyroid hormone levels were associated with adverse outcomes In the absence of definitive evidence in support of a specific parathyroid hormone target
there is an urgent need for additional research to inform clinical practice
TARGET PTH Fenotipos CKD-MBD Ca P HIGH
Ca P normal
Block G et al Clin J Am Soc Nephrol 82131-21402013
PTH 150-300 + Ca N + P N (20)
PTH gt600+ Ca N + P uarr (11) PTH 301-600+ Ca N + P uarr (16) PTH 301-600+ Ca N + P N (15)
PTH
P
P
P
P P
QUELANTES DEL P + ANTIPARATIROIDEOS
GUIAS PRAacuteCTICA CLINICA Ca P PTH valoracioacuten conjunta
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015 CM No predialysis Tolerance N ampV hypocalcemia (QT) seizures risk
TRATAMIENTOS ANTIPARATIROIDEOS
Improved survival in dialysis patients with oral vit D (967 calcitriol) in South America (n = 16004) (CORES)
Naves-Diacuteaz M et al Kidney Int 2008
bull OVERALL CARDIOVASCULAR INFECTIOUS and NEOPLASTIC mortality improved bull Unadjusted mortality rates (white bars)
bull Adjusted mortality (grey bars)
VITAMINA D ACTIVA
VITAMINA D ACTIVA Survival in HD Comparation between Paricalcitol and Calcitriol
Teng M et al N Engl J Med 2003349446ndash56
0 5 10 15 20 25 30 35 40
Paricalcitol Calcitriol
Surv
ival
()
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25 30 35 40
Surv
ival
()
Switch to calcitriol
0
10
20
30
40
50
60
70
80
90 100
Switch to paricalcitol
3-year survival 59 vs 51 Log rank plt0001
2-year survival 73 vs 64 Log rank p=004
n=67399 n=16483
Follow-up (months)
NOVEDADES TRATAMIENTO VITAMINA D Inhibidores CYP24
Calcitriol
1-α-Hidroxilasa
Guillaume Jean et Al Nephro and Ther 2009
bull CTAP 101 calcifediol de liberacioacuten retardada
bull Inhibidores CYP24
Bover J et al Expert Opinion on Pharmacotherapy 2016
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015
TRATAMIENTOS ANTIPARATIROIDEOS
MECANISMO DE ACCIOacuteN CALCIMIMEacuteTICO
Goodman WG et al Adv Renal Replace Therapy 200292000ndash8 Nemeth EF et al Proc Natl Acad Sci USA 1998954040ndash5
Serum Ca2+ Serum Ca2+ Serum Ca2+
+ cinacalcet
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
FISIOPATOLOGIA Hiperparatiroidismo secundario
Adaptado de MRodriguez amp ME Rodriacuteguez Ortiz Expert Opin Pharmacother 2015 Isakova et al KI 2011
Ca-R (-) VD-R (-)
P-R (+)
FGF23Klotho(-)
FISIOPATOLOGIA Hiperparatiroidismo secundario
Wei Ling Lau Yoshitsugu Obi and Kamyar Kalantar-Zadeh Clin J Am Soc Nephrol 2018
FISIOPATOLOGIA Hiperparatiroidismo secundario
Basile C adn Carlo Lomonte Kidney International 92 1046-1048 2017
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
FISIOPATOLOGIA PTH como ldquotoxina ureacutemicardquo
H Komaba T Kakuta M Fkagawa Clin Exp Nephrol 21S37-S45 2017
1 NKF KDOQI Am J Kidney Dis 200342(suppl 3)S1-S202) 2 KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
4 Torregrosa J-V et al Nefrologia 201131(Suppl 1)3ndash32 5Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
GUIAS PRAacuteCTICA CLINICA Target PTH
KDOQI 20031
KDIGO 20092
SEN 20114
KDIGO 20175
P 13ndash178 mmolL
(35-55 mgdl) ldquoTowardsrdquo
normal Normal
Long gap Tolerance up to 16
mmolL (5 mgdl)
ldquoTowardsrdquo normal
(including 3a-5D)
Ca Normal preferably towards the lower
end (21ndash237 mmolL)
Normal Normal Avoiding hypercalcemia
iPTH 150ndash300 ngL 2ndash9 times the upper normal range of the
assay
150ndash300 pgmL Evitar lt100 gt500 PTH
conversor (2ndash5 veces el liacutemite
superior de la normalidad para el ensayo usado)
2ndash9 times the upper normal range of the
assay
HUESO SUPERVIVENCIA
Floege J et al Nephrol Dial Transplant doi101093ndtgfq219
TARGET PTH Mortality Risk
Patients with iPTH calcium and phosphate levels within the KDOQI target ranges have the LOWEST RISK OF MORTALITY compared with those outside the target ranges
SEN 2011 5D iPTH 150-300 pgml No emergency and trends
MJ Prados-Garrido et al Dial Transpl 2011
Dialysis population (Fresenius Europe)
Recent changes in therapeutic approaches and association with outcomes among patients with SHPT on
chronic hemodialysis the DOPPS study Clin J Am Soc Nephrol 2015 Jan 710(1)98-109 Tentori F et al
RESULTS
Median parathyroid hormone increased from phase 1 to phase 4 in all regions except for Japan where it remained stable Prescriptions of intravenous vitamin D analogs and cinacalcet increased and parathyroidectomy rates decreased in all regions over time Compared with 150-300 pgml in adjusted models all-cause mortality risk was higher for parathyroid hormone=301-450 (hazard ratio 109 95 confidence interval 101 to 118) and gt600 pgml (hazard ratio 123 95 confidence interval 112 to 134) Parathyroid hormone gt600 pgml was also associated with higher risk of cardiovascular mortality as well as all-cause and cardiovascular hospitalizations In a subgroup analysis of 5387 patients not receiving vitamin D analogs or cinacalcet and with no prior parathyroidectomy very low parathyroid hormone (lt50 pgml) was associated with mortality (hazard ratio 125 95 confidence interval 104 to 151)
CONCLUSIONS
In a large international sample of patients on hemodialysis parathyroid hormone levels increased in most countries and secondary hyperparathyroidism treatments changed over time Very low and very high parathyroid hormone levels were associated with adverse outcomes In the absence of definitive evidence in support of a specific parathyroid hormone target
there is an urgent need for additional research to inform clinical practice
TARGET PTH Fenotipos CKD-MBD Ca P HIGH
Ca P normal
Block G et al Clin J Am Soc Nephrol 82131-21402013
PTH 150-300 + Ca N + P N (20)
PTH gt600+ Ca N + P uarr (11) PTH 301-600+ Ca N + P uarr (16) PTH 301-600+ Ca N + P N (15)
PTH
P
P
P
P P
QUELANTES DEL P + ANTIPARATIROIDEOS
GUIAS PRAacuteCTICA CLINICA Ca P PTH valoracioacuten conjunta
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015 CM No predialysis Tolerance N ampV hypocalcemia (QT) seizures risk
TRATAMIENTOS ANTIPARATIROIDEOS
Improved survival in dialysis patients with oral vit D (967 calcitriol) in South America (n = 16004) (CORES)
Naves-Diacuteaz M et al Kidney Int 2008
bull OVERALL CARDIOVASCULAR INFECTIOUS and NEOPLASTIC mortality improved bull Unadjusted mortality rates (white bars)
bull Adjusted mortality (grey bars)
VITAMINA D ACTIVA
VITAMINA D ACTIVA Survival in HD Comparation between Paricalcitol and Calcitriol
Teng M et al N Engl J Med 2003349446ndash56
0 5 10 15 20 25 30 35 40
Paricalcitol Calcitriol
Surv
ival
()
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25 30 35 40
Surv
ival
()
Switch to calcitriol
0
10
20
30
40
50
60
70
80
90 100
Switch to paricalcitol
3-year survival 59 vs 51 Log rank plt0001
2-year survival 73 vs 64 Log rank p=004
n=67399 n=16483
Follow-up (months)
NOVEDADES TRATAMIENTO VITAMINA D Inhibidores CYP24
Calcitriol
1-α-Hidroxilasa
Guillaume Jean et Al Nephro and Ther 2009
bull CTAP 101 calcifediol de liberacioacuten retardada
bull Inhibidores CYP24
Bover J et al Expert Opinion on Pharmacotherapy 2016
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015
TRATAMIENTOS ANTIPARATIROIDEOS
MECANISMO DE ACCIOacuteN CALCIMIMEacuteTICO
Goodman WG et al Adv Renal Replace Therapy 200292000ndash8 Nemeth EF et al Proc Natl Acad Sci USA 1998954040ndash5
Serum Ca2+ Serum Ca2+ Serum Ca2+
+ cinacalcet
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
FISIOPATOLOGIA Hiperparatiroidismo secundario
Wei Ling Lau Yoshitsugu Obi and Kamyar Kalantar-Zadeh Clin J Am Soc Nephrol 2018
FISIOPATOLOGIA Hiperparatiroidismo secundario
Basile C adn Carlo Lomonte Kidney International 92 1046-1048 2017
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
FISIOPATOLOGIA PTH como ldquotoxina ureacutemicardquo
H Komaba T Kakuta M Fkagawa Clin Exp Nephrol 21S37-S45 2017
1 NKF KDOQI Am J Kidney Dis 200342(suppl 3)S1-S202) 2 KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
4 Torregrosa J-V et al Nefrologia 201131(Suppl 1)3ndash32 5Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
GUIAS PRAacuteCTICA CLINICA Target PTH
KDOQI 20031
KDIGO 20092
SEN 20114
KDIGO 20175
P 13ndash178 mmolL
(35-55 mgdl) ldquoTowardsrdquo
normal Normal
Long gap Tolerance up to 16
mmolL (5 mgdl)
ldquoTowardsrdquo normal
(including 3a-5D)
Ca Normal preferably towards the lower
end (21ndash237 mmolL)
Normal Normal Avoiding hypercalcemia
iPTH 150ndash300 ngL 2ndash9 times the upper normal range of the
assay
150ndash300 pgmL Evitar lt100 gt500 PTH
conversor (2ndash5 veces el liacutemite
superior de la normalidad para el ensayo usado)
2ndash9 times the upper normal range of the
assay
HUESO SUPERVIVENCIA
Floege J et al Nephrol Dial Transplant doi101093ndtgfq219
TARGET PTH Mortality Risk
Patients with iPTH calcium and phosphate levels within the KDOQI target ranges have the LOWEST RISK OF MORTALITY compared with those outside the target ranges
SEN 2011 5D iPTH 150-300 pgml No emergency and trends
MJ Prados-Garrido et al Dial Transpl 2011
Dialysis population (Fresenius Europe)
Recent changes in therapeutic approaches and association with outcomes among patients with SHPT on
chronic hemodialysis the DOPPS study Clin J Am Soc Nephrol 2015 Jan 710(1)98-109 Tentori F et al
RESULTS
Median parathyroid hormone increased from phase 1 to phase 4 in all regions except for Japan where it remained stable Prescriptions of intravenous vitamin D analogs and cinacalcet increased and parathyroidectomy rates decreased in all regions over time Compared with 150-300 pgml in adjusted models all-cause mortality risk was higher for parathyroid hormone=301-450 (hazard ratio 109 95 confidence interval 101 to 118) and gt600 pgml (hazard ratio 123 95 confidence interval 112 to 134) Parathyroid hormone gt600 pgml was also associated with higher risk of cardiovascular mortality as well as all-cause and cardiovascular hospitalizations In a subgroup analysis of 5387 patients not receiving vitamin D analogs or cinacalcet and with no prior parathyroidectomy very low parathyroid hormone (lt50 pgml) was associated with mortality (hazard ratio 125 95 confidence interval 104 to 151)
CONCLUSIONS
In a large international sample of patients on hemodialysis parathyroid hormone levels increased in most countries and secondary hyperparathyroidism treatments changed over time Very low and very high parathyroid hormone levels were associated with adverse outcomes In the absence of definitive evidence in support of a specific parathyroid hormone target
there is an urgent need for additional research to inform clinical practice
TARGET PTH Fenotipos CKD-MBD Ca P HIGH
Ca P normal
Block G et al Clin J Am Soc Nephrol 82131-21402013
PTH 150-300 + Ca N + P N (20)
PTH gt600+ Ca N + P uarr (11) PTH 301-600+ Ca N + P uarr (16) PTH 301-600+ Ca N + P N (15)
PTH
P
P
P
P P
QUELANTES DEL P + ANTIPARATIROIDEOS
GUIAS PRAacuteCTICA CLINICA Ca P PTH valoracioacuten conjunta
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015 CM No predialysis Tolerance N ampV hypocalcemia (QT) seizures risk
TRATAMIENTOS ANTIPARATIROIDEOS
Improved survival in dialysis patients with oral vit D (967 calcitriol) in South America (n = 16004) (CORES)
Naves-Diacuteaz M et al Kidney Int 2008
bull OVERALL CARDIOVASCULAR INFECTIOUS and NEOPLASTIC mortality improved bull Unadjusted mortality rates (white bars)
bull Adjusted mortality (grey bars)
VITAMINA D ACTIVA
VITAMINA D ACTIVA Survival in HD Comparation between Paricalcitol and Calcitriol
Teng M et al N Engl J Med 2003349446ndash56
0 5 10 15 20 25 30 35 40
Paricalcitol Calcitriol
Surv
ival
()
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25 30 35 40
Surv
ival
()
Switch to calcitriol
0
10
20
30
40
50
60
70
80
90 100
Switch to paricalcitol
3-year survival 59 vs 51 Log rank plt0001
2-year survival 73 vs 64 Log rank p=004
n=67399 n=16483
Follow-up (months)
NOVEDADES TRATAMIENTO VITAMINA D Inhibidores CYP24
Calcitriol
1-α-Hidroxilasa
Guillaume Jean et Al Nephro and Ther 2009
bull CTAP 101 calcifediol de liberacioacuten retardada
bull Inhibidores CYP24
Bover J et al Expert Opinion on Pharmacotherapy 2016
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015
TRATAMIENTOS ANTIPARATIROIDEOS
MECANISMO DE ACCIOacuteN CALCIMIMEacuteTICO
Goodman WG et al Adv Renal Replace Therapy 200292000ndash8 Nemeth EF et al Proc Natl Acad Sci USA 1998954040ndash5
Serum Ca2+ Serum Ca2+ Serum Ca2+
+ cinacalcet
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
FISIOPATOLOGIA Hiperparatiroidismo secundario
Basile C adn Carlo Lomonte Kidney International 92 1046-1048 2017
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
FISIOPATOLOGIA PTH como ldquotoxina ureacutemicardquo
H Komaba T Kakuta M Fkagawa Clin Exp Nephrol 21S37-S45 2017
1 NKF KDOQI Am J Kidney Dis 200342(suppl 3)S1-S202) 2 KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
4 Torregrosa J-V et al Nefrologia 201131(Suppl 1)3ndash32 5Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
GUIAS PRAacuteCTICA CLINICA Target PTH
KDOQI 20031
KDIGO 20092
SEN 20114
KDIGO 20175
P 13ndash178 mmolL
(35-55 mgdl) ldquoTowardsrdquo
normal Normal
Long gap Tolerance up to 16
mmolL (5 mgdl)
ldquoTowardsrdquo normal
(including 3a-5D)
Ca Normal preferably towards the lower
end (21ndash237 mmolL)
Normal Normal Avoiding hypercalcemia
iPTH 150ndash300 ngL 2ndash9 times the upper normal range of the
assay
150ndash300 pgmL Evitar lt100 gt500 PTH
conversor (2ndash5 veces el liacutemite
superior de la normalidad para el ensayo usado)
2ndash9 times the upper normal range of the
assay
HUESO SUPERVIVENCIA
Floege J et al Nephrol Dial Transplant doi101093ndtgfq219
TARGET PTH Mortality Risk
Patients with iPTH calcium and phosphate levels within the KDOQI target ranges have the LOWEST RISK OF MORTALITY compared with those outside the target ranges
SEN 2011 5D iPTH 150-300 pgml No emergency and trends
MJ Prados-Garrido et al Dial Transpl 2011
Dialysis population (Fresenius Europe)
Recent changes in therapeutic approaches and association with outcomes among patients with SHPT on
chronic hemodialysis the DOPPS study Clin J Am Soc Nephrol 2015 Jan 710(1)98-109 Tentori F et al
RESULTS
Median parathyroid hormone increased from phase 1 to phase 4 in all regions except for Japan where it remained stable Prescriptions of intravenous vitamin D analogs and cinacalcet increased and parathyroidectomy rates decreased in all regions over time Compared with 150-300 pgml in adjusted models all-cause mortality risk was higher for parathyroid hormone=301-450 (hazard ratio 109 95 confidence interval 101 to 118) and gt600 pgml (hazard ratio 123 95 confidence interval 112 to 134) Parathyroid hormone gt600 pgml was also associated with higher risk of cardiovascular mortality as well as all-cause and cardiovascular hospitalizations In a subgroup analysis of 5387 patients not receiving vitamin D analogs or cinacalcet and with no prior parathyroidectomy very low parathyroid hormone (lt50 pgml) was associated with mortality (hazard ratio 125 95 confidence interval 104 to 151)
CONCLUSIONS
In a large international sample of patients on hemodialysis parathyroid hormone levels increased in most countries and secondary hyperparathyroidism treatments changed over time Very low and very high parathyroid hormone levels were associated with adverse outcomes In the absence of definitive evidence in support of a specific parathyroid hormone target
there is an urgent need for additional research to inform clinical practice
TARGET PTH Fenotipos CKD-MBD Ca P HIGH
Ca P normal
Block G et al Clin J Am Soc Nephrol 82131-21402013
PTH 150-300 + Ca N + P N (20)
PTH gt600+ Ca N + P uarr (11) PTH 301-600+ Ca N + P uarr (16) PTH 301-600+ Ca N + P N (15)
PTH
P
P
P
P P
QUELANTES DEL P + ANTIPARATIROIDEOS
GUIAS PRAacuteCTICA CLINICA Ca P PTH valoracioacuten conjunta
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015 CM No predialysis Tolerance N ampV hypocalcemia (QT) seizures risk
TRATAMIENTOS ANTIPARATIROIDEOS
Improved survival in dialysis patients with oral vit D (967 calcitriol) in South America (n = 16004) (CORES)
Naves-Diacuteaz M et al Kidney Int 2008
bull OVERALL CARDIOVASCULAR INFECTIOUS and NEOPLASTIC mortality improved bull Unadjusted mortality rates (white bars)
bull Adjusted mortality (grey bars)
VITAMINA D ACTIVA
VITAMINA D ACTIVA Survival in HD Comparation between Paricalcitol and Calcitriol
Teng M et al N Engl J Med 2003349446ndash56
0 5 10 15 20 25 30 35 40
Paricalcitol Calcitriol
Surv
ival
()
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25 30 35 40
Surv
ival
()
Switch to calcitriol
0
10
20
30
40
50
60
70
80
90 100
Switch to paricalcitol
3-year survival 59 vs 51 Log rank plt0001
2-year survival 73 vs 64 Log rank p=004
n=67399 n=16483
Follow-up (months)
NOVEDADES TRATAMIENTO VITAMINA D Inhibidores CYP24
Calcitriol
1-α-Hidroxilasa
Guillaume Jean et Al Nephro and Ther 2009
bull CTAP 101 calcifediol de liberacioacuten retardada
bull Inhibidores CYP24
Bover J et al Expert Opinion on Pharmacotherapy 2016
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015
TRATAMIENTOS ANTIPARATIROIDEOS
MECANISMO DE ACCIOacuteN CALCIMIMEacuteTICO
Goodman WG et al Adv Renal Replace Therapy 200292000ndash8 Nemeth EF et al Proc Natl Acad Sci USA 1998954040ndash5
Serum Ca2+ Serum Ca2+ Serum Ca2+
+ cinacalcet
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
FISIOPATOLOGIA PTH como ldquotoxina ureacutemicardquo
H Komaba T Kakuta M Fkagawa Clin Exp Nephrol 21S37-S45 2017
1 NKF KDOQI Am J Kidney Dis 200342(suppl 3)S1-S202) 2 KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
4 Torregrosa J-V et al Nefrologia 201131(Suppl 1)3ndash32 5Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
GUIAS PRAacuteCTICA CLINICA Target PTH
KDOQI 20031
KDIGO 20092
SEN 20114
KDIGO 20175
P 13ndash178 mmolL
(35-55 mgdl) ldquoTowardsrdquo
normal Normal
Long gap Tolerance up to 16
mmolL (5 mgdl)
ldquoTowardsrdquo normal
(including 3a-5D)
Ca Normal preferably towards the lower
end (21ndash237 mmolL)
Normal Normal Avoiding hypercalcemia
iPTH 150ndash300 ngL 2ndash9 times the upper normal range of the
assay
150ndash300 pgmL Evitar lt100 gt500 PTH
conversor (2ndash5 veces el liacutemite
superior de la normalidad para el ensayo usado)
2ndash9 times the upper normal range of the
assay
HUESO SUPERVIVENCIA
Floege J et al Nephrol Dial Transplant doi101093ndtgfq219
TARGET PTH Mortality Risk
Patients with iPTH calcium and phosphate levels within the KDOQI target ranges have the LOWEST RISK OF MORTALITY compared with those outside the target ranges
SEN 2011 5D iPTH 150-300 pgml No emergency and trends
MJ Prados-Garrido et al Dial Transpl 2011
Dialysis population (Fresenius Europe)
Recent changes in therapeutic approaches and association with outcomes among patients with SHPT on
chronic hemodialysis the DOPPS study Clin J Am Soc Nephrol 2015 Jan 710(1)98-109 Tentori F et al
RESULTS
Median parathyroid hormone increased from phase 1 to phase 4 in all regions except for Japan where it remained stable Prescriptions of intravenous vitamin D analogs and cinacalcet increased and parathyroidectomy rates decreased in all regions over time Compared with 150-300 pgml in adjusted models all-cause mortality risk was higher for parathyroid hormone=301-450 (hazard ratio 109 95 confidence interval 101 to 118) and gt600 pgml (hazard ratio 123 95 confidence interval 112 to 134) Parathyroid hormone gt600 pgml was also associated with higher risk of cardiovascular mortality as well as all-cause and cardiovascular hospitalizations In a subgroup analysis of 5387 patients not receiving vitamin D analogs or cinacalcet and with no prior parathyroidectomy very low parathyroid hormone (lt50 pgml) was associated with mortality (hazard ratio 125 95 confidence interval 104 to 151)
CONCLUSIONS
In a large international sample of patients on hemodialysis parathyroid hormone levels increased in most countries and secondary hyperparathyroidism treatments changed over time Very low and very high parathyroid hormone levels were associated with adverse outcomes In the absence of definitive evidence in support of a specific parathyroid hormone target
there is an urgent need for additional research to inform clinical practice
TARGET PTH Fenotipos CKD-MBD Ca P HIGH
Ca P normal
Block G et al Clin J Am Soc Nephrol 82131-21402013
PTH 150-300 + Ca N + P N (20)
PTH gt600+ Ca N + P uarr (11) PTH 301-600+ Ca N + P uarr (16) PTH 301-600+ Ca N + P N (15)
PTH
P
P
P
P P
QUELANTES DEL P + ANTIPARATIROIDEOS
GUIAS PRAacuteCTICA CLINICA Ca P PTH valoracioacuten conjunta
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015 CM No predialysis Tolerance N ampV hypocalcemia (QT) seizures risk
TRATAMIENTOS ANTIPARATIROIDEOS
Improved survival in dialysis patients with oral vit D (967 calcitriol) in South America (n = 16004) (CORES)
Naves-Diacuteaz M et al Kidney Int 2008
bull OVERALL CARDIOVASCULAR INFECTIOUS and NEOPLASTIC mortality improved bull Unadjusted mortality rates (white bars)
bull Adjusted mortality (grey bars)
VITAMINA D ACTIVA
VITAMINA D ACTIVA Survival in HD Comparation between Paricalcitol and Calcitriol
Teng M et al N Engl J Med 2003349446ndash56
0 5 10 15 20 25 30 35 40
Paricalcitol Calcitriol
Surv
ival
()
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25 30 35 40
Surv
ival
()
Switch to calcitriol
0
10
20
30
40
50
60
70
80
90 100
Switch to paricalcitol
3-year survival 59 vs 51 Log rank plt0001
2-year survival 73 vs 64 Log rank p=004
n=67399 n=16483
Follow-up (months)
NOVEDADES TRATAMIENTO VITAMINA D Inhibidores CYP24
Calcitriol
1-α-Hidroxilasa
Guillaume Jean et Al Nephro and Ther 2009
bull CTAP 101 calcifediol de liberacioacuten retardada
bull Inhibidores CYP24
Bover J et al Expert Opinion on Pharmacotherapy 2016
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015
TRATAMIENTOS ANTIPARATIROIDEOS
MECANISMO DE ACCIOacuteN CALCIMIMEacuteTICO
Goodman WG et al Adv Renal Replace Therapy 200292000ndash8 Nemeth EF et al Proc Natl Acad Sci USA 1998954040ndash5
Serum Ca2+ Serum Ca2+ Serum Ca2+
+ cinacalcet
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
FISIOPATOLOGIA PTH como ldquotoxina ureacutemicardquo
H Komaba T Kakuta M Fkagawa Clin Exp Nephrol 21S37-S45 2017
1 NKF KDOQI Am J Kidney Dis 200342(suppl 3)S1-S202) 2 KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
4 Torregrosa J-V et al Nefrologia 201131(Suppl 1)3ndash32 5Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
GUIAS PRAacuteCTICA CLINICA Target PTH
KDOQI 20031
KDIGO 20092
SEN 20114
KDIGO 20175
P 13ndash178 mmolL
(35-55 mgdl) ldquoTowardsrdquo
normal Normal
Long gap Tolerance up to 16
mmolL (5 mgdl)
ldquoTowardsrdquo normal
(including 3a-5D)
Ca Normal preferably towards the lower
end (21ndash237 mmolL)
Normal Normal Avoiding hypercalcemia
iPTH 150ndash300 ngL 2ndash9 times the upper normal range of the
assay
150ndash300 pgmL Evitar lt100 gt500 PTH
conversor (2ndash5 veces el liacutemite
superior de la normalidad para el ensayo usado)
2ndash9 times the upper normal range of the
assay
HUESO SUPERVIVENCIA
Floege J et al Nephrol Dial Transplant doi101093ndtgfq219
TARGET PTH Mortality Risk
Patients with iPTH calcium and phosphate levels within the KDOQI target ranges have the LOWEST RISK OF MORTALITY compared with those outside the target ranges
SEN 2011 5D iPTH 150-300 pgml No emergency and trends
MJ Prados-Garrido et al Dial Transpl 2011
Dialysis population (Fresenius Europe)
Recent changes in therapeutic approaches and association with outcomes among patients with SHPT on
chronic hemodialysis the DOPPS study Clin J Am Soc Nephrol 2015 Jan 710(1)98-109 Tentori F et al
RESULTS
Median parathyroid hormone increased from phase 1 to phase 4 in all regions except for Japan where it remained stable Prescriptions of intravenous vitamin D analogs and cinacalcet increased and parathyroidectomy rates decreased in all regions over time Compared with 150-300 pgml in adjusted models all-cause mortality risk was higher for parathyroid hormone=301-450 (hazard ratio 109 95 confidence interval 101 to 118) and gt600 pgml (hazard ratio 123 95 confidence interval 112 to 134) Parathyroid hormone gt600 pgml was also associated with higher risk of cardiovascular mortality as well as all-cause and cardiovascular hospitalizations In a subgroup analysis of 5387 patients not receiving vitamin D analogs or cinacalcet and with no prior parathyroidectomy very low parathyroid hormone (lt50 pgml) was associated with mortality (hazard ratio 125 95 confidence interval 104 to 151)
CONCLUSIONS
In a large international sample of patients on hemodialysis parathyroid hormone levels increased in most countries and secondary hyperparathyroidism treatments changed over time Very low and very high parathyroid hormone levels were associated with adverse outcomes In the absence of definitive evidence in support of a specific parathyroid hormone target
there is an urgent need for additional research to inform clinical practice
TARGET PTH Fenotipos CKD-MBD Ca P HIGH
Ca P normal
Block G et al Clin J Am Soc Nephrol 82131-21402013
PTH 150-300 + Ca N + P N (20)
PTH gt600+ Ca N + P uarr (11) PTH 301-600+ Ca N + P uarr (16) PTH 301-600+ Ca N + P N (15)
PTH
P
P
P
P P
QUELANTES DEL P + ANTIPARATIROIDEOS
GUIAS PRAacuteCTICA CLINICA Ca P PTH valoracioacuten conjunta
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015 CM No predialysis Tolerance N ampV hypocalcemia (QT) seizures risk
TRATAMIENTOS ANTIPARATIROIDEOS
Improved survival in dialysis patients with oral vit D (967 calcitriol) in South America (n = 16004) (CORES)
Naves-Diacuteaz M et al Kidney Int 2008
bull OVERALL CARDIOVASCULAR INFECTIOUS and NEOPLASTIC mortality improved bull Unadjusted mortality rates (white bars)
bull Adjusted mortality (grey bars)
VITAMINA D ACTIVA
VITAMINA D ACTIVA Survival in HD Comparation between Paricalcitol and Calcitriol
Teng M et al N Engl J Med 2003349446ndash56
0 5 10 15 20 25 30 35 40
Paricalcitol Calcitriol
Surv
ival
()
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25 30 35 40
Surv
ival
()
Switch to calcitriol
0
10
20
30
40
50
60
70
80
90 100
Switch to paricalcitol
3-year survival 59 vs 51 Log rank plt0001
2-year survival 73 vs 64 Log rank p=004
n=67399 n=16483
Follow-up (months)
NOVEDADES TRATAMIENTO VITAMINA D Inhibidores CYP24
Calcitriol
1-α-Hidroxilasa
Guillaume Jean et Al Nephro and Ther 2009
bull CTAP 101 calcifediol de liberacioacuten retardada
bull Inhibidores CYP24
Bover J et al Expert Opinion on Pharmacotherapy 2016
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015
TRATAMIENTOS ANTIPARATIROIDEOS
MECANISMO DE ACCIOacuteN CALCIMIMEacuteTICO
Goodman WG et al Adv Renal Replace Therapy 200292000ndash8 Nemeth EF et al Proc Natl Acad Sci USA 1998954040ndash5
Serum Ca2+ Serum Ca2+ Serum Ca2+
+ cinacalcet
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
1 NKF KDOQI Am J Kidney Dis 200342(suppl 3)S1-S202) 2 KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
4 Torregrosa J-V et al Nefrologia 201131(Suppl 1)3ndash32 5Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
GUIAS PRAacuteCTICA CLINICA Target PTH
KDOQI 20031
KDIGO 20092
SEN 20114
KDIGO 20175
P 13ndash178 mmolL
(35-55 mgdl) ldquoTowardsrdquo
normal Normal
Long gap Tolerance up to 16
mmolL (5 mgdl)
ldquoTowardsrdquo normal
(including 3a-5D)
Ca Normal preferably towards the lower
end (21ndash237 mmolL)
Normal Normal Avoiding hypercalcemia
iPTH 150ndash300 ngL 2ndash9 times the upper normal range of the
assay
150ndash300 pgmL Evitar lt100 gt500 PTH
conversor (2ndash5 veces el liacutemite
superior de la normalidad para el ensayo usado)
2ndash9 times the upper normal range of the
assay
HUESO SUPERVIVENCIA
Floege J et al Nephrol Dial Transplant doi101093ndtgfq219
TARGET PTH Mortality Risk
Patients with iPTH calcium and phosphate levels within the KDOQI target ranges have the LOWEST RISK OF MORTALITY compared with those outside the target ranges
SEN 2011 5D iPTH 150-300 pgml No emergency and trends
MJ Prados-Garrido et al Dial Transpl 2011
Dialysis population (Fresenius Europe)
Recent changes in therapeutic approaches and association with outcomes among patients with SHPT on
chronic hemodialysis the DOPPS study Clin J Am Soc Nephrol 2015 Jan 710(1)98-109 Tentori F et al
RESULTS
Median parathyroid hormone increased from phase 1 to phase 4 in all regions except for Japan where it remained stable Prescriptions of intravenous vitamin D analogs and cinacalcet increased and parathyroidectomy rates decreased in all regions over time Compared with 150-300 pgml in adjusted models all-cause mortality risk was higher for parathyroid hormone=301-450 (hazard ratio 109 95 confidence interval 101 to 118) and gt600 pgml (hazard ratio 123 95 confidence interval 112 to 134) Parathyroid hormone gt600 pgml was also associated with higher risk of cardiovascular mortality as well as all-cause and cardiovascular hospitalizations In a subgroup analysis of 5387 patients not receiving vitamin D analogs or cinacalcet and with no prior parathyroidectomy very low parathyroid hormone (lt50 pgml) was associated with mortality (hazard ratio 125 95 confidence interval 104 to 151)
CONCLUSIONS
In a large international sample of patients on hemodialysis parathyroid hormone levels increased in most countries and secondary hyperparathyroidism treatments changed over time Very low and very high parathyroid hormone levels were associated with adverse outcomes In the absence of definitive evidence in support of a specific parathyroid hormone target
there is an urgent need for additional research to inform clinical practice
TARGET PTH Fenotipos CKD-MBD Ca P HIGH
Ca P normal
Block G et al Clin J Am Soc Nephrol 82131-21402013
PTH 150-300 + Ca N + P N (20)
PTH gt600+ Ca N + P uarr (11) PTH 301-600+ Ca N + P uarr (16) PTH 301-600+ Ca N + P N (15)
PTH
P
P
P
P P
QUELANTES DEL P + ANTIPARATIROIDEOS
GUIAS PRAacuteCTICA CLINICA Ca P PTH valoracioacuten conjunta
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015 CM No predialysis Tolerance N ampV hypocalcemia (QT) seizures risk
TRATAMIENTOS ANTIPARATIROIDEOS
Improved survival in dialysis patients with oral vit D (967 calcitriol) in South America (n = 16004) (CORES)
Naves-Diacuteaz M et al Kidney Int 2008
bull OVERALL CARDIOVASCULAR INFECTIOUS and NEOPLASTIC mortality improved bull Unadjusted mortality rates (white bars)
bull Adjusted mortality (grey bars)
VITAMINA D ACTIVA
VITAMINA D ACTIVA Survival in HD Comparation between Paricalcitol and Calcitriol
Teng M et al N Engl J Med 2003349446ndash56
0 5 10 15 20 25 30 35 40
Paricalcitol Calcitriol
Surv
ival
()
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25 30 35 40
Surv
ival
()
Switch to calcitriol
0
10
20
30
40
50
60
70
80
90 100
Switch to paricalcitol
3-year survival 59 vs 51 Log rank plt0001
2-year survival 73 vs 64 Log rank p=004
n=67399 n=16483
Follow-up (months)
NOVEDADES TRATAMIENTO VITAMINA D Inhibidores CYP24
Calcitriol
1-α-Hidroxilasa
Guillaume Jean et Al Nephro and Ther 2009
bull CTAP 101 calcifediol de liberacioacuten retardada
bull Inhibidores CYP24
Bover J et al Expert Opinion on Pharmacotherapy 2016
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015
TRATAMIENTOS ANTIPARATIROIDEOS
MECANISMO DE ACCIOacuteN CALCIMIMEacuteTICO
Goodman WG et al Adv Renal Replace Therapy 200292000ndash8 Nemeth EF et al Proc Natl Acad Sci USA 1998954040ndash5
Serum Ca2+ Serum Ca2+ Serum Ca2+
+ cinacalcet
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
Floege J et al Nephrol Dial Transplant doi101093ndtgfq219
TARGET PTH Mortality Risk
Patients with iPTH calcium and phosphate levels within the KDOQI target ranges have the LOWEST RISK OF MORTALITY compared with those outside the target ranges
SEN 2011 5D iPTH 150-300 pgml No emergency and trends
MJ Prados-Garrido et al Dial Transpl 2011
Dialysis population (Fresenius Europe)
Recent changes in therapeutic approaches and association with outcomes among patients with SHPT on
chronic hemodialysis the DOPPS study Clin J Am Soc Nephrol 2015 Jan 710(1)98-109 Tentori F et al
RESULTS
Median parathyroid hormone increased from phase 1 to phase 4 in all regions except for Japan where it remained stable Prescriptions of intravenous vitamin D analogs and cinacalcet increased and parathyroidectomy rates decreased in all regions over time Compared with 150-300 pgml in adjusted models all-cause mortality risk was higher for parathyroid hormone=301-450 (hazard ratio 109 95 confidence interval 101 to 118) and gt600 pgml (hazard ratio 123 95 confidence interval 112 to 134) Parathyroid hormone gt600 pgml was also associated with higher risk of cardiovascular mortality as well as all-cause and cardiovascular hospitalizations In a subgroup analysis of 5387 patients not receiving vitamin D analogs or cinacalcet and with no prior parathyroidectomy very low parathyroid hormone (lt50 pgml) was associated with mortality (hazard ratio 125 95 confidence interval 104 to 151)
CONCLUSIONS
In a large international sample of patients on hemodialysis parathyroid hormone levels increased in most countries and secondary hyperparathyroidism treatments changed over time Very low and very high parathyroid hormone levels were associated with adverse outcomes In the absence of definitive evidence in support of a specific parathyroid hormone target
there is an urgent need for additional research to inform clinical practice
TARGET PTH Fenotipos CKD-MBD Ca P HIGH
Ca P normal
Block G et al Clin J Am Soc Nephrol 82131-21402013
PTH 150-300 + Ca N + P N (20)
PTH gt600+ Ca N + P uarr (11) PTH 301-600+ Ca N + P uarr (16) PTH 301-600+ Ca N + P N (15)
PTH
P
P
P
P P
QUELANTES DEL P + ANTIPARATIROIDEOS
GUIAS PRAacuteCTICA CLINICA Ca P PTH valoracioacuten conjunta
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015 CM No predialysis Tolerance N ampV hypocalcemia (QT) seizures risk
TRATAMIENTOS ANTIPARATIROIDEOS
Improved survival in dialysis patients with oral vit D (967 calcitriol) in South America (n = 16004) (CORES)
Naves-Diacuteaz M et al Kidney Int 2008
bull OVERALL CARDIOVASCULAR INFECTIOUS and NEOPLASTIC mortality improved bull Unadjusted mortality rates (white bars)
bull Adjusted mortality (grey bars)
VITAMINA D ACTIVA
VITAMINA D ACTIVA Survival in HD Comparation between Paricalcitol and Calcitriol
Teng M et al N Engl J Med 2003349446ndash56
0 5 10 15 20 25 30 35 40
Paricalcitol Calcitriol
Surv
ival
()
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25 30 35 40
Surv
ival
()
Switch to calcitriol
0
10
20
30
40
50
60
70
80
90 100
Switch to paricalcitol
3-year survival 59 vs 51 Log rank plt0001
2-year survival 73 vs 64 Log rank p=004
n=67399 n=16483
Follow-up (months)
NOVEDADES TRATAMIENTO VITAMINA D Inhibidores CYP24
Calcitriol
1-α-Hidroxilasa
Guillaume Jean et Al Nephro and Ther 2009
bull CTAP 101 calcifediol de liberacioacuten retardada
bull Inhibidores CYP24
Bover J et al Expert Opinion on Pharmacotherapy 2016
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015
TRATAMIENTOS ANTIPARATIROIDEOS
MECANISMO DE ACCIOacuteN CALCIMIMEacuteTICO
Goodman WG et al Adv Renal Replace Therapy 200292000ndash8 Nemeth EF et al Proc Natl Acad Sci USA 1998954040ndash5
Serum Ca2+ Serum Ca2+ Serum Ca2+
+ cinacalcet
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
Recent changes in therapeutic approaches and association with outcomes among patients with SHPT on
chronic hemodialysis the DOPPS study Clin J Am Soc Nephrol 2015 Jan 710(1)98-109 Tentori F et al
RESULTS
Median parathyroid hormone increased from phase 1 to phase 4 in all regions except for Japan where it remained stable Prescriptions of intravenous vitamin D analogs and cinacalcet increased and parathyroidectomy rates decreased in all regions over time Compared with 150-300 pgml in adjusted models all-cause mortality risk was higher for parathyroid hormone=301-450 (hazard ratio 109 95 confidence interval 101 to 118) and gt600 pgml (hazard ratio 123 95 confidence interval 112 to 134) Parathyroid hormone gt600 pgml was also associated with higher risk of cardiovascular mortality as well as all-cause and cardiovascular hospitalizations In a subgroup analysis of 5387 patients not receiving vitamin D analogs or cinacalcet and with no prior parathyroidectomy very low parathyroid hormone (lt50 pgml) was associated with mortality (hazard ratio 125 95 confidence interval 104 to 151)
CONCLUSIONS
In a large international sample of patients on hemodialysis parathyroid hormone levels increased in most countries and secondary hyperparathyroidism treatments changed over time Very low and very high parathyroid hormone levels were associated with adverse outcomes In the absence of definitive evidence in support of a specific parathyroid hormone target
there is an urgent need for additional research to inform clinical practice
TARGET PTH Fenotipos CKD-MBD Ca P HIGH
Ca P normal
Block G et al Clin J Am Soc Nephrol 82131-21402013
PTH 150-300 + Ca N + P N (20)
PTH gt600+ Ca N + P uarr (11) PTH 301-600+ Ca N + P uarr (16) PTH 301-600+ Ca N + P N (15)
PTH
P
P
P
P P
QUELANTES DEL P + ANTIPARATIROIDEOS
GUIAS PRAacuteCTICA CLINICA Ca P PTH valoracioacuten conjunta
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015 CM No predialysis Tolerance N ampV hypocalcemia (QT) seizures risk
TRATAMIENTOS ANTIPARATIROIDEOS
Improved survival in dialysis patients with oral vit D (967 calcitriol) in South America (n = 16004) (CORES)
Naves-Diacuteaz M et al Kidney Int 2008
bull OVERALL CARDIOVASCULAR INFECTIOUS and NEOPLASTIC mortality improved bull Unadjusted mortality rates (white bars)
bull Adjusted mortality (grey bars)
VITAMINA D ACTIVA
VITAMINA D ACTIVA Survival in HD Comparation between Paricalcitol and Calcitriol
Teng M et al N Engl J Med 2003349446ndash56
0 5 10 15 20 25 30 35 40
Paricalcitol Calcitriol
Surv
ival
()
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25 30 35 40
Surv
ival
()
Switch to calcitriol
0
10
20
30
40
50
60
70
80
90 100
Switch to paricalcitol
3-year survival 59 vs 51 Log rank plt0001
2-year survival 73 vs 64 Log rank p=004
n=67399 n=16483
Follow-up (months)
NOVEDADES TRATAMIENTO VITAMINA D Inhibidores CYP24
Calcitriol
1-α-Hidroxilasa
Guillaume Jean et Al Nephro and Ther 2009
bull CTAP 101 calcifediol de liberacioacuten retardada
bull Inhibidores CYP24
Bover J et al Expert Opinion on Pharmacotherapy 2016
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015
TRATAMIENTOS ANTIPARATIROIDEOS
MECANISMO DE ACCIOacuteN CALCIMIMEacuteTICO
Goodman WG et al Adv Renal Replace Therapy 200292000ndash8 Nemeth EF et al Proc Natl Acad Sci USA 1998954040ndash5
Serum Ca2+ Serum Ca2+ Serum Ca2+
+ cinacalcet
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
TARGET PTH Fenotipos CKD-MBD Ca P HIGH
Ca P normal
Block G et al Clin J Am Soc Nephrol 82131-21402013
PTH 150-300 + Ca N + P N (20)
PTH gt600+ Ca N + P uarr (11) PTH 301-600+ Ca N + P uarr (16) PTH 301-600+ Ca N + P N (15)
PTH
P
P
P
P P
QUELANTES DEL P + ANTIPARATIROIDEOS
GUIAS PRAacuteCTICA CLINICA Ca P PTH valoracioacuten conjunta
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015 CM No predialysis Tolerance N ampV hypocalcemia (QT) seizures risk
TRATAMIENTOS ANTIPARATIROIDEOS
Improved survival in dialysis patients with oral vit D (967 calcitriol) in South America (n = 16004) (CORES)
Naves-Diacuteaz M et al Kidney Int 2008
bull OVERALL CARDIOVASCULAR INFECTIOUS and NEOPLASTIC mortality improved bull Unadjusted mortality rates (white bars)
bull Adjusted mortality (grey bars)
VITAMINA D ACTIVA
VITAMINA D ACTIVA Survival in HD Comparation between Paricalcitol and Calcitriol
Teng M et al N Engl J Med 2003349446ndash56
0 5 10 15 20 25 30 35 40
Paricalcitol Calcitriol
Surv
ival
()
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25 30 35 40
Surv
ival
()
Switch to calcitriol
0
10
20
30
40
50
60
70
80
90 100
Switch to paricalcitol
3-year survival 59 vs 51 Log rank plt0001
2-year survival 73 vs 64 Log rank p=004
n=67399 n=16483
Follow-up (months)
NOVEDADES TRATAMIENTO VITAMINA D Inhibidores CYP24
Calcitriol
1-α-Hidroxilasa
Guillaume Jean et Al Nephro and Ther 2009
bull CTAP 101 calcifediol de liberacioacuten retardada
bull Inhibidores CYP24
Bover J et al Expert Opinion on Pharmacotherapy 2016
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015
TRATAMIENTOS ANTIPARATIROIDEOS
MECANISMO DE ACCIOacuteN CALCIMIMEacuteTICO
Goodman WG et al Adv Renal Replace Therapy 200292000ndash8 Nemeth EF et al Proc Natl Acad Sci USA 1998954040ndash5
Serum Ca2+ Serum Ca2+ Serum Ca2+
+ cinacalcet
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
PTH
P
P
P
P P
QUELANTES DEL P + ANTIPARATIROIDEOS
GUIAS PRAacuteCTICA CLINICA Ca P PTH valoracioacuten conjunta
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015 CM No predialysis Tolerance N ampV hypocalcemia (QT) seizures risk
TRATAMIENTOS ANTIPARATIROIDEOS
Improved survival in dialysis patients with oral vit D (967 calcitriol) in South America (n = 16004) (CORES)
Naves-Diacuteaz M et al Kidney Int 2008
bull OVERALL CARDIOVASCULAR INFECTIOUS and NEOPLASTIC mortality improved bull Unadjusted mortality rates (white bars)
bull Adjusted mortality (grey bars)
VITAMINA D ACTIVA
VITAMINA D ACTIVA Survival in HD Comparation between Paricalcitol and Calcitriol
Teng M et al N Engl J Med 2003349446ndash56
0 5 10 15 20 25 30 35 40
Paricalcitol Calcitriol
Surv
ival
()
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25 30 35 40
Surv
ival
()
Switch to calcitriol
0
10
20
30
40
50
60
70
80
90 100
Switch to paricalcitol
3-year survival 59 vs 51 Log rank plt0001
2-year survival 73 vs 64 Log rank p=004
n=67399 n=16483
Follow-up (months)
NOVEDADES TRATAMIENTO VITAMINA D Inhibidores CYP24
Calcitriol
1-α-Hidroxilasa
Guillaume Jean et Al Nephro and Ther 2009
bull CTAP 101 calcifediol de liberacioacuten retardada
bull Inhibidores CYP24
Bover J et al Expert Opinion on Pharmacotherapy 2016
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015
TRATAMIENTOS ANTIPARATIROIDEOS
MECANISMO DE ACCIOacuteN CALCIMIMEacuteTICO
Goodman WG et al Adv Renal Replace Therapy 200292000ndash8 Nemeth EF et al Proc Natl Acad Sci USA 1998954040ndash5
Serum Ca2+ Serum Ca2+ Serum Ca2+
+ cinacalcet
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015 CM No predialysis Tolerance N ampV hypocalcemia (QT) seizures risk
TRATAMIENTOS ANTIPARATIROIDEOS
Improved survival in dialysis patients with oral vit D (967 calcitriol) in South America (n = 16004) (CORES)
Naves-Diacuteaz M et al Kidney Int 2008
bull OVERALL CARDIOVASCULAR INFECTIOUS and NEOPLASTIC mortality improved bull Unadjusted mortality rates (white bars)
bull Adjusted mortality (grey bars)
VITAMINA D ACTIVA
VITAMINA D ACTIVA Survival in HD Comparation between Paricalcitol and Calcitriol
Teng M et al N Engl J Med 2003349446ndash56
0 5 10 15 20 25 30 35 40
Paricalcitol Calcitriol
Surv
ival
()
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25 30 35 40
Surv
ival
()
Switch to calcitriol
0
10
20
30
40
50
60
70
80
90 100
Switch to paricalcitol
3-year survival 59 vs 51 Log rank plt0001
2-year survival 73 vs 64 Log rank p=004
n=67399 n=16483
Follow-up (months)
NOVEDADES TRATAMIENTO VITAMINA D Inhibidores CYP24
Calcitriol
1-α-Hidroxilasa
Guillaume Jean et Al Nephro and Ther 2009
bull CTAP 101 calcifediol de liberacioacuten retardada
bull Inhibidores CYP24
Bover J et al Expert Opinion on Pharmacotherapy 2016
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015
TRATAMIENTOS ANTIPARATIROIDEOS
MECANISMO DE ACCIOacuteN CALCIMIMEacuteTICO
Goodman WG et al Adv Renal Replace Therapy 200292000ndash8 Nemeth EF et al Proc Natl Acad Sci USA 1998954040ndash5
Serum Ca2+ Serum Ca2+ Serum Ca2+
+ cinacalcet
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
Improved survival in dialysis patients with oral vit D (967 calcitriol) in South America (n = 16004) (CORES)
Naves-Diacuteaz M et al Kidney Int 2008
bull OVERALL CARDIOVASCULAR INFECTIOUS and NEOPLASTIC mortality improved bull Unadjusted mortality rates (white bars)
bull Adjusted mortality (grey bars)
VITAMINA D ACTIVA
VITAMINA D ACTIVA Survival in HD Comparation between Paricalcitol and Calcitriol
Teng M et al N Engl J Med 2003349446ndash56
0 5 10 15 20 25 30 35 40
Paricalcitol Calcitriol
Surv
ival
()
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25 30 35 40
Surv
ival
()
Switch to calcitriol
0
10
20
30
40
50
60
70
80
90 100
Switch to paricalcitol
3-year survival 59 vs 51 Log rank plt0001
2-year survival 73 vs 64 Log rank p=004
n=67399 n=16483
Follow-up (months)
NOVEDADES TRATAMIENTO VITAMINA D Inhibidores CYP24
Calcitriol
1-α-Hidroxilasa
Guillaume Jean et Al Nephro and Ther 2009
bull CTAP 101 calcifediol de liberacioacuten retardada
bull Inhibidores CYP24
Bover J et al Expert Opinion on Pharmacotherapy 2016
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015
TRATAMIENTOS ANTIPARATIROIDEOS
MECANISMO DE ACCIOacuteN CALCIMIMEacuteTICO
Goodman WG et al Adv Renal Replace Therapy 200292000ndash8 Nemeth EF et al Proc Natl Acad Sci USA 1998954040ndash5
Serum Ca2+ Serum Ca2+ Serum Ca2+
+ cinacalcet
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
VITAMINA D ACTIVA Survival in HD Comparation between Paricalcitol and Calcitriol
Teng M et al N Engl J Med 2003349446ndash56
0 5 10 15 20 25 30 35 40
Paricalcitol Calcitriol
Surv
ival
()
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25 30 35 40
Surv
ival
()
Switch to calcitriol
0
10
20
30
40
50
60
70
80
90 100
Switch to paricalcitol
3-year survival 59 vs 51 Log rank plt0001
2-year survival 73 vs 64 Log rank p=004
n=67399 n=16483
Follow-up (months)
NOVEDADES TRATAMIENTO VITAMINA D Inhibidores CYP24
Calcitriol
1-α-Hidroxilasa
Guillaume Jean et Al Nephro and Ther 2009
bull CTAP 101 calcifediol de liberacioacuten retardada
bull Inhibidores CYP24
Bover J et al Expert Opinion on Pharmacotherapy 2016
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015
TRATAMIENTOS ANTIPARATIROIDEOS
MECANISMO DE ACCIOacuteN CALCIMIMEacuteTICO
Goodman WG et al Adv Renal Replace Therapy 200292000ndash8 Nemeth EF et al Proc Natl Acad Sci USA 1998954040ndash5
Serum Ca2+ Serum Ca2+ Serum Ca2+
+ cinacalcet
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
NOVEDADES TRATAMIENTO VITAMINA D Inhibidores CYP24
Calcitriol
1-α-Hidroxilasa
Guillaume Jean et Al Nephro and Ther 2009
bull CTAP 101 calcifediol de liberacioacuten retardada
bull Inhibidores CYP24
Bover J et al Expert Opinion on Pharmacotherapy 2016
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015
TRATAMIENTOS ANTIPARATIROIDEOS
MECANISMO DE ACCIOacuteN CALCIMIMEacuteTICO
Goodman WG et al Adv Renal Replace Therapy 200292000ndash8 Nemeth EF et al Proc Natl Acad Sci USA 1998954040ndash5
Serum Ca2+ Serum Ca2+ Serum Ca2+
+ cinacalcet
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
bull CTAP 101 calcifediol de liberacioacuten retardada
bull Inhibidores CYP24
Bover J et al Expert Opinion on Pharmacotherapy 2016
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015
TRATAMIENTOS ANTIPARATIROIDEOS
MECANISMO DE ACCIOacuteN CALCIMIMEacuteTICO
Goodman WG et al Adv Renal Replace Therapy 200292000ndash8 Nemeth EF et al Proc Natl Acad Sci USA 1998954040ndash5
Serum Ca2+ Serum Ca2+ Serum Ca2+
+ cinacalcet
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
Table 1 Comparison of distinct effects of P binders and anti-parathyroid agents on CKD-MBD laboratory parameters progression of vascular calcification (VC) andor survival Ca = Calcium P = Phosphate PTH = Parathyroid hormone NA = Not available RCT = Randomized Clinical Trial Exp = only experimental studies
Bover et al NDT 2015
TRATAMIENTOS ANTIPARATIROIDEOS
MECANISMO DE ACCIOacuteN CALCIMIMEacuteTICO
Goodman WG et al Adv Renal Replace Therapy 200292000ndash8 Nemeth EF et al Proc Natl Acad Sci USA 1998954040ndash5
Serum Ca2+ Serum Ca2+ Serum Ca2+
+ cinacalcet
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
MECANISMO DE ACCIOacuteN CALCIMIMEacuteTICO
Goodman WG et al Adv Renal Replace Therapy 200292000ndash8 Nemeth EF et al Proc Natl Acad Sci USA 1998954040ndash5
Serum Ca2+ Serum Ca2+ Serum Ca2+
+ cinacalcet
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
INTEGRAL PHARMACOLOGICAL MANAGEMENT OF BONE MINERAL DISORDERS IN CHRONIC KIDNEY DISEASE From treatment of phosphate imbalance (part I) to control of PTH and prevention of progression of cardiovascular calcification (part II) JBover PUrentildea MJ Lloret CRuiz IDaSilva MDiaz-Encarnacion CMercado SMateu EFernandez JBallariacuten
Expert Opinion on Pharmacotherapy 2016 Published on line
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
Adherencia tolerancia Naacuteuseas y Voacutemitos excesiva darr PTH hipocalcemia (QT)
Prospective studies ADVANCE EVOLVE Potencial darr progresioacuten calcificacioacuten CV y uarr supervivencia
Clin J Am Soc Nephrol 2016
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
ADHERENCIA
Chiu YW et al Clin J Am Soc Nephrol 20094(6)1089-1096
Media de comprimidos en paciente en HD 19 compdiacutea
bull Paciente croacutenico polimedicado Falta de riesgo inmediato bull Se evitan teacuterminos punitivos (no cumplidor) Diferencias entre adherencia
intencionadano-intencionada bull Partnership Empatiacutea Autonomiacutea bull La falta de adherencia tiene un alto coste econoacutemico directo e indirecto
(hospitalizaciones)
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
Cinacalcet12 Etelcalcetide3489
Clase Calcimimeacutetico Calcimimetico
Descripcioacuten Pequentildea moleacutecula orgaacutenica
Peacuteptido sinteacutetico agonista de 7 AA unido a L-cisteina
Tamantildeo PM = 3939 gmol PM =10483 gmol
Mec accioacuten Interaccioacuten con segmentos de membrane del RSCa y aumenta la sentildeal de transduccioacuten reduciendo asiacute la secrecioacuten PTH
Interacciona y activa el RSCa reduciendo la secrecioacuten de PTH
Admin Oral diaria EV al final de la session de diaacutelisis en bolus
1 Mimparareg (cinacalcet) Summary of product characteristics Amgen 2 Goodman WG Adv Ren Replace Ther 20029200-208 3 Cunningham J et al Presented at the 52nd ERA-EDTA Congress May 2015 London UK 4 Chen P et al J Clin Pharmacol 201555620-628 5 Goodman WG et al Kidney Int 200874276-288 6 Moallem E et al J Biol Chem 19982735253-5259 7 Brown EM Rev Endocr Metab Disord 20001307-315 8 Walter S et al J Pharmacol Exp Ther 2013346229-240 9 Amgen Media News Release Amgen submits new drug application for novel intravenous calcimimetic etelcalcetide (AMG 416)
ETELCALCETIDA ES UN NUEVO CALCIMIMEacuteTICO EV
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
ETECALCETIDA VERSUS PLACEBO
Block et al JAMA 2017317 (2)146-155
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
Estudio comparativo de no-inferioridad Head2Head
ETECALCETIDA VERSUS CINACALCET
Block et al JAMA 2017
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
HIPOCALCEMIA-GUIAS KDIGO 2017
2017 2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
J Am Heart Asoc 2014
bull Greater relative benefit on nonatherosclerotic CV events including sudden death and heart failure
bull The potential CV benefit of cinacalcet in HD patients
may be mediated by nonatherosclerotic mechanisms
slowing arterial calcification or reducing myocardial Ca accumulation
darr FGF-23 darr LVH
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
Scialla and Wolf Nature 2014
FISIOPATOLOGIA Toxicidad de FGF-23
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
472
162 157
949 894
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
GUIAS ndash ELECCIOacuteN DE ANTIPARATIROIDEO
2017
2009
KDIGO CKD Work Group Kidney Int 2013Suppl 31ndash150
Ketteler al KDIGO 2017 Kidney Int Suppl 201771ndash59
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
Revisiting KDIGO clinical practice guideline on CKD-MBD a commentary from KDIGO controversies conference
Ketteler M et al Kidney Int 2015
The group was unanimous in their assesment of the clinical significance of CV calcification and the conclusion that CV calcification SHOULD BE CONSIDERED for guidance of CKD-MBD management However they concluded that there was INSUFFICIENT NEW EVIDENCE to warrant a reasessment of these statements Specifically no high-quality data have been published to justify ROUTINE screening and no new data comparing different imaging methods have emerged The overall perception of the WG was that the available data may indeed strengthen the existing clinical practice guideline but updating the evidence rating was outside the scope of the conference since no systematic review was performed a priori on this issue
CKD-MBD CALCIFICACIOacuteN VASCULAR
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
CKDndashMBD SYSTEMIC DISORDER
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
Prevention of vascular calcification in a CKD rat model
Yu L et al CTIN 2017
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
ABORDAJE TERAPEacuteUTICO DEL HPS
JBover PUrentildea MJLloret et al Expert opinion 2016
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
Conclusiones
bull El complejo CKD-MBD estaacute asociado a patologiacutea oacutesea vascular y un aumento de morbimortalidad en pacientes en diaacutelisis
bull Nuevos derivados de la VD estaacuten en fase de desarrollo pero cambios en ldquoUS market dynamicsrdquo estaacuten retrasando su desarrollo
bull La falta de tolerabilidad y cumplimiento terapeacuteutico con cinacalcet ha derivado en el desarrollo de un nuevo calcimimeacutetico por viacutea EV
bull Etelcalcetida EV es maacutes eficaz que cinacalcet oral para el tratamiento del HPS en pacientes en diaacutelisis pudiendo mejorar el cumplimiento terapeacuteutico
