Long-term effects of renin-angiotensin system-blocking therapy and a low blood pressure goal on progression of hypertensive chronic kidney disease in African Americans.

BACKGROUND Antihypertensive drugs that block the renin-angiotensin system (angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers) are recommended for patients with chronic kidney disease (CKD). A low blood pressure (BP) goal (BP, <130/80 mm Hg) is also recommended. The objective of this study was to determine the long-term effects of currently recommended BP therapy in 1094 African Americans with hypertensive CKD. METHODS Multicenter cohort study following a randomized trial. Participants were 1094 African Americans with hypertensive renal disease (glomerular filtration rate, 20-65 mL/min/1.73 m2). Following a 3x2-factorial trial (1995-2001) that tested 3 drugs used as initial antihypertensive therapy (ACEIs, calcium channel blockers, and beta-blockers) and 2 levels of BP control (usual and low), we conducted a cohort study (2002-2007) in which participants were treated with ACEIs to a BP lower than 130/80 mm Hg. The outcome measures were a composite of doubling of the serum creatinine level, end-stage renal disease, or death. RESULTS During each year of the cohort study, the annual use of an ACEI or an angiotensin receptor blocker ranged from 83.7% to 89.0% (vs 38.5% to 49.8% during the trial). The mean BP in the cohort study was 133/78 mm Hg (vs 136/82 mm Hg in the trial). Overall, 567 participants experienced the primary outcome; the 10-year cumulative incidence rate was 53.9%. Of 576 participants with at least 7 years of follow-up, 33.5% experienced a slow decline in kidney function (mean annual decline in the estimated glomerular filtration rate, <1 mL/min/1.73 m2). CONCLUSION Despite the benefits of renin-angiotensin system-blocking therapy on CKD progression, most African Americans with hypertensive CKD who are treated with currently recommended BP therapy continue to progress during the long term.

[1]  P. Whelton,et al.  The excess incidence of diabetic end-stage renal disease among blacks. A population-based study of potential explanatory factors. , 1992, JAMA.

[2]  G. Striker Modification of diet in renal disease. , 1992, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[3]  G. Remuzzi,et al.  Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial , 1998, The Lancet.

[4]  Keith C. Norris,et al.  Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. , 2001, JAMA.

[5]  N. Sato,et al.  Long-term effect of eicosapentaenoic acid ethyl (EPA-E) on albuminuria of non-insulin dependent diabetic patients. , 1995, Diabetes research and clinical practice.

[6]  H. Morita,et al.  Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. , 2003, Lancet.

[7]  H. Dustan,et al.  Renal insufficiency in treated essential hypertension. , 1989, The New England journal of medicine.

[8]  J. Kalbfleisch,et al.  The Statistical Analysis of Failure Time Data , 1980 .

[9]  D. Brotman,et al.  Association of impaired diurnal blood pressure variation with a subsequent decline in glomerular filtration rate. , 2006, Archives of internal medicine.

[10]  Lawrence Appel,et al.  Validation of creatinine-based estimates of GFR when evaluating risk factors in longitudinal studies of kidney disease. , 2006, Journal of the American Society of Nephrology : JASN.

[11]  J. Klein,et al.  Survival Analysis: Techniques for Censored and Truncated Data , 1997 .

[12]  L. Appel,et al.  Baseline characteristics of participants in the African American Study of Kidney Disease and Hypertension (AASK) Clinical Trial and Cohort Study. , 2007, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[13]  H. Morita,et al.  RETRACTED: Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial , 2003, The Lancet.

[14]  M. Hughson,et al.  Antioxidant Treatment Prevents Renal Damage and Dysfunction and Reduces Arterial Pressure in Salt-Sensitive Hypertension , 2005, Hypertension.

[15]  G. Beck,et al.  The Effects of Dietary Protein Restriction and Blood-Pressure Control on the Progression of Chronic Renal Disease , 1994 .

[16]  V. Torres,et al.  Long-Term Ammonium Chloride or Sodium Bicarbonate Treatment in Two Models of Polycystic Kidney Disease , 2001, Nephron Experimental Nephrology.

[17]  R. Gray A Class of $K$-Sample Tests for Comparing the Cumulative Incidence of a Competing Risk , 1988 .

[18]  J. Cutler,et al.  Renal function change in hypertensive members of the Multiple Risk Factor Intervention Trial. Racial and treatment effects. The MRFIT Research Group. , 1992 .

[19]  R. D. Manning,et al.  Renal NF-κB activation and TNF-α upregulation correlate with salt-sensitive hypertension in Dahl salt-sensitive rats , 2006 .

[20]  Christopher H Schmid,et al.  Progression of Chronic Kidney Disease: The Role of Blood Pressure Control, Proteinuria, and Angiotensin-Converting Enzyme Inhibition: A Patient-Level Meta-Analysis , 2003, Annals of Internal Medicine.

[21]  Tom Greene,et al.  Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. , 2002, JAMA.

[22]  Di Xie,et al.  Efficacy and safety of benazepril for advanced chronic renal insufficiency. , 2006, The New England journal of medicine.

[23]  T. Pickering,et al.  The role of ambulatory blood pressure monitoring in chronic and end-stage renal disease. , 2006, Kidney international.

[24]  Charles E. McCulloch,et al.  Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. , 2004, The New England journal of medicine.

[25]  M. Kutner,et al.  Design and statistical aspects of the African American Study of Kidney Disease and Hypertension (AASK). , 2003, Journal of the American Society of Nephrology : JASN.

[26]  C. Schmid,et al.  Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data. , 2001, Annals of internal medicine.

[27]  E. Vittinghoff,et al.  Racial differences in the progression from chronic renal insufficiency to end-stage renal disease in the United States. , 2003, Journal of the American Society of Nephrology : JASN.

[28]  J. Coresh,et al.  Prevalence of high blood pressure and elevated serum creatinine level in the United States: findings from the third National Health and Nutrition Examination Survey (1988-1994). , 2001, Archives of internal medicine.

[29]  J. Lewis,et al.  Comparison of cross-sectional renal function measurements in African Americans with hypertensive nephrosclerosis and of primary formulas to estimate glomerular filtration rate. , 2001, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[30]  W. McClellan,et al.  Racial differences in the incidence of hypertensive end-stage renal disease (ESRD) are not entirely explained by differences in the prevalence of hypertension. , 1988, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[31]  Daniel W. Jones,et al.  Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. , 2003, Hypertension.

[32]  Keith C. Norris,et al.  The rationale and design of the AASK cohort study. , 2003, Journal of the American Society of Nephrology : JASN.

[33]  Bruce Kupelnick,et al.  K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease , 2004 .

[34]  Laurence L. George,et al.  The Statistical Analysis of Failure Time Data , 2003, Technometrics.

[35]  M. Tonelli,et al.  Progression of kidney dysfunction in the community-dwelling elderly. , 2006, Kidney international.

[36]  T. Hostetter,et al.  Aldosterone in chronic kidney and cardiac disease. , 2003, Journal of the American Society of Nephrology : JASN.

[37]  P. Whelton,et al.  Blood pressure and end-stage renal disease in men. , 1996, The New England journal of medicine.

[38]  V. Pavlik,et al.  Characteristics of patients with uncontrolled hypertension in the United States. , 2001, The New England journal of medicine.

[39]  Daniel W. Jones,et al.  The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. , 2003, JAMA.