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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 Meta Análise: Menor PAM retarda progressão da DRC em diabéticos e não-diabéticos MAP (mmHg) 95 98 101 104 107 110 113 116 119 0 GFR (mL/min/year) -2 r = 0.69; P < 0.05 -4 -6 Untreated HTN -8 -10 -12 130/85 140/90 -14 Bakris GL, et al. Am J Kidney Dis. 2000;36(3):646-661. 2 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? - 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): 188-95 Nx DM 1 - IECA e nefroproteção 40 409 pacientes Cr> 1,5 mg/dL Prot > 2,7 g/24 horas Captopril T. Convencional 30 Progressão para Morte, Diálise ou Transplante 20 * (%) 10 0 0 1 2 3 4 Anos * p = 0.006 vs placebo. Lewis EJ et al. N Engl J Med 1993;329:1456-1462. 6 MENSAGEM 1 Controle pressórico se associa a nefroproteção, em especial por meio do uso de IECAs Meta-análise IECA reduz progressão DRC, não Mortes Giatras, I et al, 1997 United Kingdom Prospective Diabetes 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 Heart Outcomes Prevention Evaluation: Ramipril reduziu eventos C-V e progressão DRC 0 Nefropatia IAM AVC Morte CV -5 -10 -15 % -20 -25 -30 N=3.677 -35 Lancet 2000;355:253-259 RENAAL: Resumo de Desfechos de Composto Primário e Clínicos Porcentagem de Redução de Risco(95% CI) 2xCr / IRCT / Morte IRCT Morte IRCT ou morte +50 0 favorece Losartana -50 favorece Placebo de Zeeuw et al. 2004 IDNT: PAS BAIXA REDUZIU EVENTOS RENAIS EM DIABETICOS IDNT – JASN 2005;16;3027-37 Effects of intensive blood pressure reduction on myocardial infarction and stroke in diabetes: a meta-analysis in 73 913 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, 29:1253–1269 McBrien and cols Arch Intern Med. 2012;172(17):1296-1303. NEJM, 2010 TRATAMENTO INTENSIVO NÃO REDUZIU EVENTOS C-V NEJM, 2010 MENSAGEM 2 Controle pressórico retarda progressão da DRC mas NÃO reduz eventos cardiovasculares de modo consistente 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? - APENAS 3 ESTUDOS EM NEFROLOGIA Decline in glomerular filtration rate (ml/mm) CIAL ARTICLE www.jasn.org MDRD– SEM DIFERENÇA DESFECHOS 0 Low blood pressure group Usual blood pressure group 3 6 9 12 (n=840) 15 B3 F4 F12 F20 F28 F36 Month after randomization e 1. Estimated mean SE decline in the GFR from baseline (B) to selected w-up times (F) in MDRD. The patients who were assigned to the usual-BP group Lazarus J et al. Hypertension 1997;29:641-650 ed line) are compared with those assigned to the low-BP group (solid line). Adapted 32 Mean rate of GFR decline (ml/min/yr) 1. Estimated mean SE decline in the GFR from baseline (B) to p times (F) in MDRD. The patients who were assigned to the usualMDRD - SUBANÁLISE line) are compared with those assigned to the low-BP group (solid line) ahr et al.,32 with permission. Study A - GFR 25-55 ml/min Study B – GFR 13-24 ml/min 0 0 4 4 8 8 12 n = 420 n = 104 n = 54 n = 136 n = 63 n = 32 <1 1–<3 3 <1 1–<3 3 12 Base-line urinary protein (g/day) 2. Decline in the GFR according to baseline urinary protein excretio n MDRD. The mean SE rate of decline per year in the GFR from bas REIN Study: ACE Inhibition in Proteinuric NonDiabetic Nephropathy % of patients without combined endpoint* *Combined endpoint = doubling of baseline serum creatinine concentration or end stage renal failure 100 80 Ramipril 60 40 P=0.02 20 Placebo 0 0 6 12 18 24 30 36 Baseline SBP ∆ SBP Baseline DBP ∆ DBP Ramipril 149.8 -5.8 mmHg 92.4 -4.2 mmHg Placebo 148.0 -3.4 mmHg 91.3 -3.4 mmHg The GISEN Group. Lancet. 1997;349:1857–1863. American African Study of Kidney Diseases and Hypertension (AASK) 1094 hipertensos negros com lesão renal e, não diabéticos Clearence entre 20 – 65 ml/min (3 a 6,4 anos) 3 fármacos: Ramipril, Anlodipino e Metoprolol 2 níveis de PAM: < 92 mmHg e 102-107 mmHg Desfechos: Redução do RFG > 50% ou 25 ml/min - TRS JAMA 2002 AASK – Arch Int Med, 2002 AASK STUDY 141 x 85 mmHg 128 x 78 mmHg PA Author Manuscript 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 NIH-PA Author Manuscript 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. NIH-PA Author Manuscr 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 MENSAGEM 3 CONTROLE PRESSÓRICO RIGOROSO NÃO MELHORA DESFECHOS RENAIS ANÁLISE DE SUBGRUPOS COM PROTEINÚRIA SIGNIFICATIVA SUGEREM BENEFICIOS COM REDUÇÃO INTENSIVA DA PA 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? - Proteinuria as a Risk Factor for Mortality in Type 2 Diabetes Survival (all - cause mortality) 1.0 Normoalbuminuria (n=191) 0.9 Microalbuminuria (n=86) 0.8 0.7 Macroalbuminuria (n=51) 0.6 0.5 0 P<0.01 P<0.001 P<0.05 1 2 3 4 5 6 Years Normo vs micro Normo vs macro Micro vs macro Gall MA, et al. Diabetes. 1995;44:1303-09 R E eduction nd Points N oninsulinDM A ngiotensin A ntagonist Proteinuria Basal Prediz Eventos Renais de Zeeuw et al, 2004 L osartan PA Author Manuscript 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 NIH-PA Author Manuscript 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. NIH-PA Author Manuscr 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 Mean rate of GFR decline (ml/min/yr) 1. Estimated mean SE decline in the GFR from baseline (B) to p times (F) in MDRD. MDRD The patients who were assigned to the usual- SUBANÁLISE line) are compared with those assigned to the low-BP group (solid line) ahr et al.,32 with permission. Study A - GFR 25-55 ml/min Study B – GFR 13-24 ml/min 0 0 4 4 8 8 12 n = 420 n = 104 n = 54 n = 136 n = 63 n = 32 <1 1–<3 3 <1 1–<3 3 12 Base-line urinary protein (g/day) 2. Decline in the GFR according to baseline urinary protein excretio n MDRD. The mean SE rate of decline per year in the GFR from bas Jafar TH and cols Ann Intern Med 2003;139:244 N=9.287 11 estudos Jicheng Lv et al. CMAJ 2013;185:949-957 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? - Thomopoulosa C et al Journal of Hypertension 2016, 34:613–622 MENSAGEM 4 CUIDADO COM POPULAÇÕES DE RISCO INDIVIDUALIZE ! 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 BP Control CHM-JF – Real Life SBP basal SBP final DBP basal DBP final De Paula EA and cols - NDT 29 Suppl 3, 2014 De Paula EA and cols - NDT 29 Suppl 3, 2014 MENSAGEM FINAL META INFERIOR A 130 X 80 mmHg PARECE EFICAZ, EM ESPECIAL NA PRESENÇA DE ALBUMINURIA QUAL O PONTO DE CORTE INFERIOR??? - ACCORD Cushman WC. NEJM 2010;362: 1575-1585
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