View
103
Download
0
Category
Preview:
Citation preview
Impacto metabólico e estratégias para redução do risco cardiovascular em DP
Roberto Pecoits-Filho
Potential conflict of interest
• Honoraria– Gambro, Altana, Baxter, Renal Research Institute, Roche,
University of Missouri, Genzyme • Research Grants
– CNPq, Fundação Araucária, Fundação Pro Renal, Baxter, Astra Zeneca, Amgen, Biogenerix, Genzyme
• Consulting– Crescendo Medical Education (www.thekidney.org), Baxter,
Roche, Genzyme
Kramer HJ et al J Am Soc Nephrol 2006; 17:1453-9
Chan J, et al Nephrology Dialysis Transplantation 2007; 22(4):1100-1106
Bone remodeling
Acute phase reactants
Partialy corrected uremia
Muscle catabolism
Endothelial dysfunction Monocyte adhesion SMC proliferation LDL oxidation appetite
REE
adipocytokine production
Increased innate immune responseDeffective adaptive immune response
Insulin resistyanceMetabolic syndrome
• Lameire et al – 5 casos de de novo diabetes mellitus em 310 pacientes não
diabéticos entre 1979 and 1996
• Outras séries– de novo diabetes em 5% de pacientes
Lameire N, et al. Clin Nephrol 1988; 30 (Suppl 1): S53-58.Kurtz SB, et al. Mayo Clin Proc 1983; 58: 633-639.
Hiperglicemia pós PDHiperglicemia pós PD
• Glicemia de jejum (fasting after overnight dwell with 1.5% glucose)
• 153 DM / 252 non-DM patients
• Fasting plasma glucose – 126 - 200 mg/dL - 48 patients (19.0%) – >200mg/dl – 11 patients (4.4%)
New Onset Hyperglycemia in Non-Diabetic Chinese Patients New Onset Hyperglycemia in Non-Diabetic Chinese Patients Started on Peritoneal DialysisStarted on Peritoneal Dialysis
Szeto CC. Am J Kidney Dis 2007 Apr;49(4):524-32.
Gordura corporal em PD
Fernstrom at al PDI, Vol 18, pp. 166-171, 1998
Peso KG 67.1 68.4 ns
% Gordura 27.8 30.9 ns
Gordura abdominal (cm2) 130.1 159.7 P<0.02
Dexa CT scans, 12 pacientes incidentes
Disturbances of carbohydrate metabolism in non-diabetic PD patients
PD HD p value Fasting glucose (mg/dL) 90±16 81±14 <0.005
1 (%)HbA C 6.1±0.8 5.4±0.5 <0.0001 1 > 7%HbA c (%) 6 0 <0.005
HOMA index 3.3±3.2 2.1±2.0 <0.05 Fibrinogen ( /mg dL) 582±183 452±183 <0.001
Fortes et al. ISPD Hong Kong 2006
Metabolic Syndrome and Dialysis
Fortes et al. ASN 2006
%
Davies et al, KI, 1998 and Peritoneal Davies et al, KI, 1998 and Peritoneal Biopsy RegistryBiopsy Registry®®
00..66
00..6655
00..77
00..7755
11 66 1122 1188 2244 3300 3366 4422 4488 5544 6600
MMoonntthhss oonn PPeerriittoonneeaall DDiiaallyyssiiss
So
lute
Tra
nsp
ort
(D
/P c
reat
)
Changes in membrane structure and Changes in membrane structure and function with time on PDfunction with time on PD
Increased vascular area in experimental diabetes
De Vriese et al. JASN 2001; 12 1734-41
Problemas metabólicos aumentam nos alto transportadores
Reabsorção de glicose Obesidade
Dislipidemia
Resistência insulínica
Aumento da perda proteica Hipoalbuminemia
Perda da capacidade antioxidante
Edema
Falha de UF Sobrecarga de volume
Inflamação
Aumento de mortalidade
ADEMEX : Diabetes Mellitus
p=0.3237
p=0.7203
Months on Study
% P
atie
nt S
urv
ival
follow up (months)
0 6 12 18 24 30 36
act
uari
al s
urv
iva
l
0.5
0.6
0.7
0.8
0.9
1.0
pre-existing diabetes
FBS < 100 mg/dL
FBS 100 to 126 mg/dL
univariate Cox regression, p = 0.020
FBS > 126 mg/dL
Fasting blood glucose predicts survival in PD patientsFasting blood glucose predicts survival in PD patients
Szeto CC. Am J Kidney Dis 2007 Apr;49(4):524-32.
Abbott KG et alKidney Int 2004; 65:597-605
BMI≥30
BMI<30
BMI≥30
BMI<30
HD PD
Obesidade reduz a sobrevida de pacientes Obesidade reduz a sobrevida de pacientes em PDem PD
McDonald SP et al J Am Soc Nephrol 2003; 14: 2894-901
N=9769Obesity HR 1.35
<20
20-24.9
25-29.9>30
P<0.001
Diferenças da relação entre mortalidade Diferenças da relação entre mortalidade e obesidade: PD e HDe obesidade: PD e HD
• Em diálise peritoneal– a obesidade está relacionada a risco de
complicações de cateter e infecções– Mais frequentemente relacionada a acúmulo de
gordura no abdomen– Mais frequentemente associada a distúrbios
metabólicos
Morioka et al: Diabetes Care 24: 909-913, 2001
P = 0.005
Wu et al: NDT 12: 2105-10, 1997
Programas de redução de peso em PDProgramas de redução de peso em PD
• 11 pacientes com mais de 25 de IMC• Equipe multidisciplinar
– Refeições planejadas – Programa de exercícios– Otimização de prescrição
Hollis J et al Perit Dial Int 25(Suppl 3): S152-4, 2005
Weight reduction program in PDWeight reduction program in PD
Hollis J et al Perit Dial Int 25(Suppl 3): S152-4, 2005
N=8 0 mo 12 mo P value
Weight (kg) 94.6 89.5 0.017
Energy intake (kcal/d)
1824 1208 0.012
PD energy (kcal/d) 350 339 NS
PD volume (L/d) 8.75 10.75 NS
Kt/V 2.26 2.28 NS
% Body fat 41.2 40.2 NS
Volume 17, 2001
Adapted from Johnson DW et al Icodextrin as salvage therapy in peritoneal dialysis patients with refractory fluid overload BMC Nephrology 2001,2 :2
8.97.9
5
5.5
6
6.5
7
7.5
8
8.5
9
9.5
HbA
1c %
Glucose Icodextrin
* P <0.05
Substitution of one glucose exchange with icodextrin results in a significant fall in HbA1c
Prospective, open label study of 17 PD patients with symptomatic fluid overload
A subset of 12 insulin treated diabetic APD and CAPD patients
Substitution of one 4.25% for Extraneal. All other exchanges remained the same
*
Baseline 1 month post Icodextrin
ResultsInsulin dose
0 3 6 9 12
-15
-10
-5
0
5
10GLU
ICO
* p<0.05 ICO vs GLU+p<0.01 ICO vs GLU
+++
++++**
*
Months
In
sulin
dos
e (U
/d)
ResultsBlood glucose
Mean±EEM*p<0.05; ** p<0.03; *** p<0.01 vs Control‡p<0.05; ‡ ‡ p<0.03; ‡ ‡ ‡ p<0.01 vs Basal
Mean±EEM*p<0.05; ** p<0.03; *** p<0.01 vs Control‡p<0.05; ‡ ‡ p<0.03; ‡ ‡ ‡ p<0.01 vs Basal
0 3 6 9 12
-100
-75
-50
-25
0
25
50
75
100GLU
ICO
* p<0.05 ICO vs GLU
**
Months
F
asti
ng s
erum
Glu
cose
(m
g/dL
)
ResultsGlycated hemoglobin
Mean±EEM*p<0.05; ** p<0.03; *** p<0.01 vs Control‡p<0.05; ‡ ‡ p<0.03; ‡ ‡ ‡ p<0.01 vs Basal
Mean±EEM*p<0.05; ** p<0.03; *** p<0.01 vs Control‡p<0.05; ‡ ‡ p<0.03; ‡ ‡ ‡ p<0.01 vs Basal
0 3 6 9 12
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
0.5
1.0
1.5
2.0GLU
ICO
* p<0.05 ICO vs GLU+p<0.01 ICO vs GLU
* *
+
+
Months
H
b a1
c (%
)
ResultsTriglycerides
Mean±EEM*p<0.05; ** p<0.03; *** p<0.01 vs Control‡p<0.05; ‡ ‡ p<0.03; ‡ ‡ ‡ p<0.01 vs Basal
Mean±EEM*p<0.05; ** p<0.03; *** p<0.01 vs Control‡p<0.05; ‡ ‡ p<0.03; ‡ ‡ ‡ p<0.01 vs Basal
0 3 6 9 12
-200
-150
-100
-50
0
50
100GLU
ICO
* p<0.05 ICO vs GLU+p<0.01 ICO vs GLU
+
+
Months
S
erum
Tri
glyc
erid
es(m
g/dL
)
ResultsSurvival
Mean±EEM*p<0.05; ** p<0.03; *** p<0.01 vs Control‡p<0.05; ‡ ‡ p<0.03; ‡ ‡ ‡ p<0.01 vs Basal
Mean±EEM*p<0.05; ** p<0.03; *** p<0.01 vs Control‡p<0.05; ‡ ‡ p<0.03; ‡ ‡ ‡ p<0.01 vs Basal
0 3 6 9 12 1550
60
70
80
90
100GLU
ICO
log-rank test p<0.01
Time
Per
cent
sur
viva
l
NEPP
DDDD
PPPP
Marshall J et al. Kidney Int 2003; 64: 1480-1486
4D Study4D Study
Wanner C et al N Engl J Med 2005; 353(3):238-48
Fellstrom B et al. N Engl J Med 2009;10.1056/NEJMoa0810177
AURORA
Paciente DRC/ HD / DP
•Colesterol Total•TG
•HDL, LDL
Perfil patológico•TG>180mg%•LDL>100mg%•HDL<40mg%
Sem perfil patológico
Cada 6 meses:•Colesterol•TG•HDL, LDL
Hiperlipidemia combinadaestatinas
Metat: LDL<1oomg%
HipertligiceridemiaGemfibrozil
Meta:: TG<180mg%
Não combine!!
Cada 6 meses:•Colesterol•TG•HDL, LDL•Enzimas hepaticas
NDT 2000: Vol 15, Suppl. 5
Martens FM, et al. Drugs 2002; 62: 1463-1480.
52 DM with Stable glycemic control on insulin on PD
Insulin + Add on RSZ 4mg daily
Insulin alone
Randomized24 wks
Wong et al. Am J Kidney Dis 2005 Oct;46(4):713-9
Improve Insulin Resistance Percentage reduction in insulin dosage was markedly more
significant in RSZ group than control group [-21% vs -0.5%]
Wong TY, …, Li PKT. Am J Kidney Dis 2005 Oct;46(4):713-9
Change in hsCRPse
rum
CR
P (
mg
/L)
0
2
4
6
8
10
12
14
0 week 24 week
TZD CTL TZD CTL
p = 0.03p = 0.01
Wong TY, …, Li PKT. Am J Kidney Dis 2005 Oct;46(4):713-9
Longitudinal Assessment of Numerous Discrete
Modifications of Atherosclerotic Risk factors in Kidney disease
LANDMARKLANDMARK
Isbel NM et al Am Heart J 2006; 151(3):745-53
(N=200)(49 PD, 78 HD, 73 pre-dialysis)
LANDMARK TrialLANDMARK TrialParameter Usual Care Focused Care Visits 2 Monthly Monthly Smoking Usual Psych, QUIT Lipids TC<5.5,
LDL<3 TC<4, LDL<2,
TG<2 Hcy No Target Hcy<15 BP 160/90 <140/90 Hb 10-12.5 11-12.5 Pi <1.8 <1.6 PTH 2-3 x N 2-3 x N HbA1C No Target <8% Aspirin Clinical Indicn All Patients
Isbel NM et al Am Heart J 2006; 151(3):745-53
0.00
0.25
0.50
0.75
1.00
Cum
ulat
ive
Sur
viva
l
0 5 10 15 20 25Survival (months of follow up)
randomis = 1 randomis = 2
Event free survival by randomization group
Isbel NM et al Am Heart J 2006; 151(3):745-53
Usual Care Vs Focus Care
HD vs. PD in DMUSRDS Mortality 1987-2005
First year
Third year
Second Year
Courtesy Dr. Heaf
Conclusões
• Alterações do metabolismo de glicose e lípides são comuns em DRC
• Absorção de glicose piora os distúrbios em DP, particularmente em alto transportadores
• Intervenções são eficazes • Redução na mortalidade ainda precisa ser demonstrada
Recommended