Impacto metabólico e estratégias para redução do risco cardiovascular em DP Roberto Pecoits-Filho.

Apresentação em tema: "Impacto metabólico e estratégias para redução do risco cardiovascular em DP Roberto Pecoits-Filho."— Transcrição da apresentação:

1 Impacto metabólico e estratégias para redução do risco cardiovascular em DP Roberto Pecoits-Filho

2 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

3 Kramer HJ et al J Am Soc Nephrol 2006; 17:1453-9

4 Chan J, et al Nephrology Dialysis Transplantation 2007; 22(4):1100-1106

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8  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 response Deffective adaptive immune response  Insulin resistyance  Metabolic syndrome

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10 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 PD

11 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 Started on Peritoneal Dialysis Szeto CC. Am J Kidney Dis 2007 Apr;49(4):524-32.

12 Gordura corporal em PD Fernstrom at al PDI, Vol 18, pp. 166-171, 1998 Peso KG 67.168.4ns % Gordura 27.830.9ns Gordura abdominal (cm2) 130.1159.7P<0.02 Dexa CT scans, 12 pacientes incidentes

13 Disturbances of carbohydrate metabolism in non-diabetic PD patients Fortes et al. ISPD Hong Kong 2006

14 Metabolic Syndrome and Dialysis Fortes et al. ASN 2006 %

15 Davies et al, KI, 1998 and Peritoneal Biopsy Registry ® 0.6 0.65 0.7 0.75 16121824303642485460 Months on Peritoneal Dialysis Solute Transport (D/P creat) Changes in membrane structure and function with time on PD

16 Increased vascular area in experimental diabetes De Vriese et al. JASN 2001; 12 1734-41

17 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

18 ADEMEX : Diabetes Mellitus p=0.3237 p=0.7203 Months on Study % Patient Survival

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20 Fasting blood glucose predicts survival in PD patients Szeto CC. Am J Kidney Dis 2007 Apr;49(4):524-32.

21 Abbott KG et alKidney Int 2004; 65:597-605 BMI≥30 BMI<30 BMI≥30 BMI<30 HD PD

22 Obesidade reduz a sobrevida de pacientes em PD McDonald SP et al J Am Soc Nephrol 2003; 14: 2894-901 N=9769 Obesity HR 1.35 <20 20-24.9 25-29.9 >30 P<0.001

23 Diferenças da relação entre mortalidade e 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

24 Morioka et al: Diabetes Care 24: 909-913, 2001 P = 0.005 Wu et al: NDT 12: 2105-10, 1997

25 Programas 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

26 Weight reduction program in PD Hollis J et al Perit Dial Int 25(Suppl 3): S152-4, 2005 N=80 mo12 moP value Weight (kg)94.689.50.017 Energy intake (kcal/d)182412080.012 PD energy (kcal/d)350339NS PD volume (L/d)8.7510.75NS Kt/V2.262.28NS % Body fat41.240.2NS

27 Volume 17, 2001

28 Adapted from Johnson DW et al Icodextrin as salvage therapy in peritoneal dialysis patients with refractory fluid overload BMC Nephrology 2001,2 :2 8.9 7.9 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5 HbA1c % GlucoseIcodextrin * 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 * Baseline1 month post Icodextrin

29 Results Insulin dose

30 Results Blood 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

31 Results Glycated 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

32 Results Triglycerides 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

33 Results Survival 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

34 NEPP DDDD PPPP Marshall J et al. Kidney Int 2003; 64: 1480-1486

35 4D Study Wanner C et al N Engl J Med 2005; 353(3):238-48

36 Fellstrom B et al. N Engl J Med 2009;10.1056/NEJMoa0810177 AURORA

37 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 combinada estatinas Metat: LDL<1oomg% Hipertligiceridemia Gemfibrozil Meta:: TG<180mg% Não combine!! Cada 6 meses: Colesterol TG HDL, LDL Enzimas hepaticas NDT 2000: Vol 15, Suppl. 5

38 Martens FM, et al. Drugs 2002; 62: 1463-1480.

39 52 DM with Stable glycemic control on insulin on PD Insulin + Add on RSZ 4mg daily Insulin alone Randomized 24 wks Wong et al. Am J Kidney Dis 2005 Oct;46(4):713-9

40 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

41 Change in hsCRP Wong TY, …, Li PKT. Am J Kidney Dis 2005 Oct;46(4):713-9

42 L ongitudinal A ssessment of N umerous D iscrete M odifications of A therosclerotic R isk factors in K idney disease LANDMARK Isbel NM et al Am Heart J 2006; 151(3):745-53 (N=200) (49 PD, 78 HD, 73 pre-dialysis)

43 LANDMARK Trial Isbel NM et al Am Heart J 2006; 151(3):745-53

44 Usual Care Vs Focus Care

45 HD vs. PD in DM USRDS Mortality 1987-2005 First year Third year Second Year Courtesy Dr. Heaf

46 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

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