REDUZIR A PRESSÃO ARTERIAL PARA VALORES ABAIXO DE 130 x 80 É BENÉFICO NO PACIENTE HIPERTENSO COM NEFROPATIA DIABÉTICA OU NÃO ASSOCIADA?

Transcrição

1 REDUZIR A PRESSÃO ARTERIAL PARA VALORES ABAIXO DE 130 x 80 É BENÉFICO NO PACIENTE HIPERTENSO COM NEFROPATIA DIABÉTICA OU NÃO ASSOCIADA? ROGÉRIO BAUMGRATZ DE PAULA PROFESSOR TITULAR - NEFROLOGIA UNIVERSIDADE FEDERAL DE JUIZ DE FORA - MG

2 GFR (ml/min/year) Meta Análise: Menor PAM retarda progressão da DRC em diabéticos e não-diabéticos MAP (mmhg) r = 0.69; P < Untreated HTN /85 140/90 Bakris GL, et al. Am J Kidney Dis. 2000;36(3):

3 Meta pressórica de 130 x 80 mmhg é apropriada para o paciente com DRC? 1- NEFROPROTEÇÃO EM DIABÉTICOS 2- NEFROPROTEÇÃO EM NÃO DIABÉTICOS 3- PROTEINÚRIA COMO MARCADOR 4- QUAL A META? -

4 11 diabéticos tipo 1 Hidralazina, Metoprolol e Furosemida PA inicial: 143 x 96 mmhg PA final: 130 x 84 mmhg Parving HH and cols 4 Am J Kidney Dis, 1993;22(1):

5 Nx DM 1 - IECA e nefroproteção Captopril T. Convencional 409 pacientes Cr> 1,5 mg/dl Prot > 2,7 g/24 horas Progressão para Morte, Diálise ou Transplante (%) * * p = vs placebo Anos Lewis EJ et al. N Engl J Med 1993;329:

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7 MENSAGEM 1 Controle pressórico se associa a nefroproteção, em especial por meio do uso de IECAs

8 Meta-análise IECA reduz progressão DRC, não Mortes Giatras, I et al, 1997

9 United KingdomProspectiveDiabetes Study Controle da PA salva vidas Controle intensivo (n=1.148): 144 / 85 vs 154 / 74 mmhg Qualquer evento final relacionado ao DM Eventos microvasculares finais Infarto do miocárdio Mortes relacionadas ao diabetes Acidente vascular cerebral 24% 37% 21% 32% 44% p = 0,005 p = 0,009 p = 0,130 p = 0,017 p = 0,013 BMJ, 1998

10 Heart Outcomes Prevention Evaluation: Ramipril reduziu eventos C-V e progressão DRC 0-5 Nefropatia IAM AVC Morte CV % N=3.677 Lancet 2000;355:

11 RENAAL: Resumo de Desfechos de Composto Primário e Clínicos Porcentagem de Redução de Risco(95% CI) 2xCr / IRCT / Morte IRCT Morte IRCT ou morte favorece Losartana favorece Placebo de Zeeuw et al. 2004

12 IDNT: PAS BAIXA REDUZIU EVENTOS RENAIS EM DIABETICOS

13 IDNT JASN 2005;16;

14 Effects of intensive blood pressure reduction on myocardial infarction and stroke in diabetes: a meta-analysis in patients Conclusion: In patients with diabetes, protection from stroke increases with the magnitude of BP reduction. We were unable to detect such a relation for MI. Journal of Hypertension 2011, 29:

15 McBrien and cols Arch Intern Med. 2012;172(17):

16 NEJM, 2010

17 TRATAMENTO INTENSIVO NÃO REDUZIU EVENTOS C-V NEJM, 2010

18 MENSAGEM 2 Controle pressórico retarda progressão da DRC mas NÃO reduz eventos cardiovasculares de modo consistente

19 Meta pressórica de 130 x 80 mmhg é apropriada para o paciente com DRC? 1- NEFROPROTEÇÃO EM DIABÉTICOS 2- NEFROPROTEÇÃO EM NÃO DIABÉTICOS 3- PROTEINÚRIA COMO MARCADOR 4- QUAL A META? -

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21 APENAS 3 ESTUDOS EM NEFROLOGIA

22 Decline in glomerular filtration rate (ml/mm) IAL ARTICLE MDRD SEM DIFERENÇA DESFECHOS 0 3 Low blood pressure group Usual blood pressure group B3 (n=840) F4 F12 F20 F28 F36 Month after randomization 1. Estimated mean SE decline in the GFR from baseline (B) to selected -up times (F) in MDRD. The Lazarus patients J et al. Hypertension who were assigned 1997;29: to the usual-bp group d line) are compared with those assigned to the low-bp group (solid line). Adapted 32

23 Mean rate of GFR decline (ml/min/yr). Decline in the GFR according to baseline urinary protein excretio MDRD. The mean SE rate of decline per year in the GFR from bas. Estimated mean SE decline in the GFR from baseline (B) to times (F) in MDRD. The patients who were assigned to the usualline) are compared with those assigned to the low-bp group (solid line) MDRD - SUBANÁLISE hr et al., 32 with permission. Study A - GFR ml/min Study B GFR ml/min n = 420 n = 104 n = 54 n = 136 n = 63 n = 32 <1 1 <3 3 <1 1 <3 3 Base-line urinary protein (g/day) 12

24 % of patients without combined endpoint* REIN Study: ACE Inhibition in Proteinuric Non- Diabetic Nephropathy *Combined endpoint = doubling of baseline serum creatinine concentration or end stage renal failure Ramipril P=0.02 Placebo Baseline SBP SBP Baseline DBP DBP Ramipril mmhg mmhg Placebo mmhg mmhg The GISEN Group. Lancet. 1997;349:

25 American African Study of Kidney Diseases and Hypertension (AASK) 1094 hipertensos negros com lesão renal e, não diabéticos Clearence entre ml/min (3 a 6,4 anos) 3 fármacos: Ramipril, Anlodipino e Metoprolol 2 níveis de PAM: < 92 mmhg e mmhg Desfechos: Redução do RFG > 50% ou 25 ml/min - TRS JAMA 2002

26 AASK Arch Int Med, 2002 AASK STUDY 141 x 85 mmhg 128 x 78 mmhg

27 A Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscr Intensive Blood-Pressure Control in Hypertensive Chronic Kidney Disease Lawrence J. Appel, M.D., M.P.H., Jackson T. Wright Jr., M.D., Ph.D., Tom Greene, Ph.D., Lawrence Y. Agodoa, M.D., Brad C. Astor, M.P.H., Ph.D., George L. Bakris, M.D., William H. Cleveland, M.D., Jeanne Charleston, R.N., Gabriel Contreras, M.D., M.P.H., Marquetta L. Faulkner, M.D., Francis B. Gabbai, M.D., Jennifer J. Gassman, Ph.D., Lee A. Hebert, M.D., Kenneth A. Jamerson, M.D., Joel D. Kopple, M.D., M.P.H., John W. Kusek, Ph.D., James P. Lash, M.D., Janice P. Lea, M.D., Julia B. Lewis, M.D., Michael S. Lipkowitz, M.D., Shaul G. Massry, M.D., Edgar R. Miller, Ph.D., M.D., Keith Norris, M.D., Robert A. Phillips, M.D., Ph.D., Velvie A. Pogue, M.D., Otelio S. Randall, M.D., Stephen G. Rostand, M.D., Miroslaw J. Smogorzewski, M.D., Robert D. Toto, M.D., and Xuelei Wang, M.S. * for the AASK Collaborative Research Group Abstract BACKGROUND In observational studies, the relationship between blood pressure and endstage renal disease (ESRD) is direct and progressive. The burden of hypertension-related chronic kidney disease and ESRD is especially high among black patients. Yet few trials have tested whether intensive blood-pressure control retards the progression of chronic kidney disease among black patients. METHODS We randomly assigned 1094 black patients with hypertensive chronic kidney disease to receive either intensive or standard blood-pressure control. After completing the trial phase, patients were invited to enroll in a cohort phase in which the blood-pressure target was less than 130/80 mm Hg. The primary clinical outcome in the cohort phase was the progression of chronic kidney disease, which was defined as a doubling of the serum creatinine level, a diagnosis of ESRD, or death. Follow-up ranged from 8.8 to 12.2 years. RESULTS During the trial phase, the mean blood pressure was 130/78 mm Hg in the intensivecontrol group and 141/86 mm Hg in the standard-control group. During the cohort phase, corresponding mean blood pressures were 131/78 mm Hg and 134/78 mm Hg. In both phases, there was no significant between-group difference in the risk of the primary outcome (hazard ratio in the intensive-control group, 0.91; P = 0.27). However, the effects differed according to the baseline level of proteinuria (P = 0.02 for interaction), with a potential benefit in patients with a protein-to-creatinine ratio of more than 0.22 (hazard ratio, 0.73; P = 0.01). CONCLUSIONS In overall analyses, intensive blood-pressure control had no effect on kidney disease progression. However, there may be differential effects of intensive blood-pressure control in patients with and those without baseline proteinuria. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center on Minority Health and Health Disparities, and others.) AASK NEJM 2010

28 MENSAGEM 3 CONTROLE PRESSÓRICO RIGOROSO NÃO MELHORA DESFECHOS RENAIS ANÁLISE DE SUBGRUPOS COM PROTEINÚRIA SIGNIFICATIVA SUGEREM BENEFICIOS COM REDUÇÃO INTENSIVA DA PA

29 Meta pressórica de 130 x 80 mmhg é apropriada para o paciente com DRC? 1- NEFROPROTEÇÃO EM DIABÉTICOS 2- NEFROPROTEÇÃO EM NÃO DIABÉTICOS 3- PROTEINÚRIA COMO MARCADOR 4- QUAL A META? -

30 Survival (all - cause mortality) Proteinuria as a Risk Factor for Mortality in Type 2 Diabetes Normoalbuminuria (n=191) Microalbuminuria (n=86) Macroalbuminuria (n=51) Years P<0.01 P<0.001 P<0.05 Normo vs micro Normo vs macro Micro vs macro Gall MA, et al. Diabetes. 1995;44:

31 ReductionEnd PointsNoninsulinDMAngiotensinAntagonistLosartan Proteinuria Basal Prediz Eventos Renais de Zeeuw et al, 2004

32 A Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscr Intensive Blood-Pressure Control in Hypertensive Chronic Kidney Disease Lawrence J. Appel, M.D., M.P.H., Jackson T. Wright Jr., M.D., Ph.D., Tom Greene, Ph.D., Lawrence Y. Agodoa, M.D., Brad C. Astor, M.P.H., Ph.D., George L. Bakris, M.D., William H. Cleveland, M.D., Jeanne Charleston, R.N., Gabriel Contreras, M.D., M.P.H., Marquetta L. Faulkner, M.D., Francis B. Gabbai, M.D., Jennifer J. Gassman, Ph.D., Lee A. Hebert, M.D., Kenneth A. Jamerson, M.D., Joel D. Kopple, M.D., M.P.H., John W. Kusek, Ph.D., James P. Lash, M.D., Janice P. Lea, M.D., Julia B. Lewis, M.D., Michael S. Lipkowitz, M.D., Shaul G. Massry, M.D., Edgar R. Miller, Ph.D., M.D., Keith Norris, M.D., Robert A. Phillips, M.D., Ph.D., Velvie A. Pogue, M.D., Otelio S. Randall, M.D., Stephen G. Rostand, M.D., Miroslaw J. Smogorzewski, M.D., Robert D. Toto, M.D., and Xuelei Wang, M.S. * for the AASK Collaborative Research Group Abstract BACKGROUND In observational studies, the relationship between blood pressure and endstage renal disease (ESRD) is direct and progressive. The burden of hypertension-related chronic kidney disease and ESRD is especially high among black patients. Yet few trials have tested whether intensive blood-pressure control retards the progression of chronic kidney disease among black patients. METHODS We randomly assigned 1094 black patients with hypertensive chronic kidney disease to receive either intensive or standard blood-pressure control. After completing the trial phase, patients were invited to enroll in a cohort phase in which the blood-pressure target was less than 130/80 mm Hg. The primary clinical outcome in the cohort phase was the progression of chronic kidney disease, which was defined as a doubling of the serum creatinine level, a diagnosis of ESRD, or death. Follow-up ranged from 8.8 to 12.2 years. RESULTS During the trial phase, the mean blood pressure was 130/78 mm Hg in the intensivecontrol group and 141/86 mm Hg in the standard-control group. During the cohort phase, corresponding mean blood pressures were 131/78 mm Hg and 134/78 mm Hg. In both phases, there was no significant between-group difference in the risk of the primary outcome (hazard ratio in the intensive-control group, 0.91; P = 0.27). However, the effects differed according to the baseline level of proteinuria (P = 0.02 for interaction), with a potential benefit in patients with a protein-to-creatinine ratio of more than 0.22 (hazard ratio, 0.73; P = 0.01). CONCLUSIONS In overall analyses, intensive blood-pressure control had no effect on kidney disease progression. However, there may be differential effects of intensive blood-pressure control in patients with and those without baseline proteinuria. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center on Minority Health and Health Disparities, and others.) AASK NEJM 2010

33 Mean rate of GFR decline (ml/min/yr). Decline in the GFR according to baseline urinary protein excretio MDRD. The mean SE rate of decline per year in the GFR from bas. Estimated mean SE decline in the GFR from baseline (B) to times (F) in MDRD. MDRD The patients - SUBANÁLISE who were assigned to the usualline) are compared with those assigned to the low-bp group (solid line) hr et al., 32 with permission. Study A - GFR ml/min Study B GFR ml/min n = 420 n = 104 n = 54 n = 136 n = 63 n = 32 <1 1 <3 3 <1 1 <3 3 Base-line urinary protein (g/day) 12

34 Jafar TH and cols Ann Intern Med 2003;139:244

35 N= estudos Jicheng Lv et al. CMAJ 2013;185:

36 Meta pressórica de 130 x 80 mmhg é apropriada para o paciente com DRC? 1- NEFROPROTEÇÃO EM DIABÉTICOS 2- NEFROPROTEÇÃO EM NÃO DIABÉTICOS 3- PROTEINÚRIA COMO MARCADOR 4- QUAL A META? -

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40 Thomopoulosa C et al Journal of Hypertension 2016, 34:

41 MENSAGEM 4 CUIDADO COM POPULAÇÕES DE RISCO INDIVIDUALIZE!

42 RENAL FUNCTION TRAJECTORY IN CHRONIC KIDNEY DISEASE PATIENTS: RESULTS OF A REAL-LIFE STUDY E. A. de Paula, C. P. Vanelli, M. S. Caminhas, B. C. Soares, F. A. Bassoli, D. M. da Costa, C. M. Lanna, A. G. Galil, F. A. Colugnati, M. B. Costa, M. G. Bastos, R. B. de Paula ERA-EDTA, 2014

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44 BP Control CHM-JF Real Life SBP SBP DBP DBP basal final basal final De Paula EA and cols - NDT 29 Suppl 3, 2014

45 De Paula EA and cols - NDT 29 Suppl 3, 2014

46 MENSAGEM FINAL META INFERIOR A 130 X 80 mmhg PARECE EFICAZ, EM ESPECIAL NA PRESENÇA DE ALBUMINURIA QUAL O PONTO DE CORTE INFERIOR??? -

47 ACCORD Cushman WC. NEJM 2010;362: