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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