1.
Effects of blood pressure level on progression of diabetic nephropathy: results from the RENAAL study.
Bakris, GL, Weir, MR, Shanifar, S, Zhang, Z, Douglas, J, van Dijk, DJ, Brenner, BM, ,
Archives of internal medicine. 2003;(13):1555-65
Abstract
BACKGROUND Clinical trials of nephropathy in people with type 2 diabetes mellitus have not examined the effects of systolic blood pressure (SBP) or pulse pressure (PP) on the time to end-stage renal disease (ESRD) or death. OBJECTIVES To evaluate the impact of baseline and treated SBP, diastolic blood pressure (DBP), and PP on composite and individual outcomes including doubling of serum creatinine, ESRD, or death in participants of the Reduction of Endpoints in NIDDM (non-insulin-dependent diabetes mellitus) With the Angiotensin II Antagonist Losartan (RENAAL) Study; to assess the specific effect of the angiotensin receptor blocker losartan potassium on composite and renal outcomes; and to explore the implications of dihydropyridine calcium channel blockers as concurrent therapy on composite and renal outcomes. DESIGN A Cox proportional hazards regression model was used to assess the hazard risk profile of baseline SBP (categories: <130, 130-139, 140-159, 160-179, and > or =180 mm Hg), DBP (categories: <70, 70-79, 80-89, 90-99, and > or =100 mm Hg), and PP (categories: <60, 60-69, 70-79, 80-89, and > or =90 mm Hg) on renal outcomes. PARTICIPANTS The study comprised 1513 participants with established nephropathy and hypertension associated with type 2 diabetes. INTERVENTIONS The RENAAL study was a randomized, placebo-controlled study of losartan vs placebo, with other agents added to achieve the goal of a trough BP (ie, BP immediately prior to the next dosing) below 140/90 mm Hg, and had a mean follow-up of 3.4 years. MAIN OUTCOME MEASURES The primary analysis was time to composite end point of doubling of serum creatinine, ESRD, or death. RESULTS A baseline SBP range of 140 to 159 mm Hg increased risk for ESRD or death by 38% (P =.05) compared with those below 130 mm Hg. In a multivariate model, every 10-mm Hg rise in baseline SBP increased the risk for ESRD or death by 6.7% (P =.007); the same rise in DBP decreased the risk by 10.9% (P =.01) when adjusting for urinary albumin-creatinine ratio, serum creatinine, serum albumin, hemoglobin, and hemoglobin A1c. Those randomized to the losartan group with a baseline PP above 90 mm Hg had a 53.5% risk reduction for ESRD alone (P =.003) and a 35.5% risk reduction for ESRD or death (P =.02) compared with the placebo group. CONCLUSIONS Baseline SBP is a stronger predictor than DBP of renal outcomes in those with nephropathy resulting from type 2 diabetes. Those with the highest baseline PP have the highest risk for nephropathy progression but also garner the greatest risk reduction with SBP lowered to less than 140 mm Hg.
2.
Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy.
Brenner, BM, Cooper, ME, de Zeeuw, D, Keane, WF, Mitch, WE, Parving, HH, Remuzzi, G, Snapinn, SM, Zhang, Z, Shahinfar, S, et al
The New England journal of medicine. 2001;(12):861-9
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Abstract
BACKGROUND Diabetic nephropathy is the leading cause of end-stage renal disease. Interruption of the renin-angiotensin system slows the progression of renal disease in patients with type 1 diabetes, but similar data are not available for patients with type 2, the most common form of diabetes. We assessed the role of the angiotensin-II-receptor antagonist losartan in patients with type 2 diabetes and nephropathy. METHODS A total of 1513 patients were enrolled in this randomized, double-blind study comparing losartan (50 to 100 mg once daily) with placebo, both taken in addition to conventional antihypertensive treatment (calcium-channel antagonists, diuretics, alpha-blockers, beta-blockers, and centrally acting agents), for a mean of 3.4 years. The primary outcome was the composite of a doubling of the base-line serum creatinine concentration, end-stage renal disease, or death. Secondary end points included a composite of morbidity and mortality from cardiovascular causes, proteinuria, and the rate of progression of renal disease. RESULTS A total of 327 patients in the losartan group reached the primary end point, as compared with 359 in the placebo group (risk reduction, 16 percent; P=0.02). Losartan reduced the incidence of a doubling of the serum creatinine concentration (risk reduction, 25 percent; P=0.006) and end-stage renal disease (risk reduction, 28 percent; P=0.002) but had no effect on the rate of death. The benefit exceeded that attributable to changes in blood pressure. The composite of morbidity and mortality from cardiovascular causes was similar in the two groups, although the rate of first hospitalization for heart failure was significantly lower with losartan (risk reduction, 32 percent; P=0.005). The level of proteinuria declined by 35 percent with losartan (P<0.001 for the comparison with placebo). CONCLUSIONS Losartan conferred significant renal benefits in patients with type 2 diabetes and nephropathy, and it was generally well tolerated.
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[Effect of losartan on renal and cardiovascular complications of patients with type 2 diabetes and nephropathy].
Parving, HH, Brenner, BM, Cooper, ME, de Zeeuw, D, Keane, WF, Mitch, WE, Remuzzi, G, Snapinn, SM, Zhang, Z, Shahinfar, S
Ugeskrift for laeger. 2001;(40):5514-9
Abstract
INTRODUCTION Diabetic nephropathy is the leading cause of end-stage renal disease. Interruption of the renin-angiotensin system slows the progression of renal disease in type 1 diabetic patients, but similar data are not available for type 2, the most common form of diabetes. We assessed the role of the angiotensin II receptor antagonist, losartan, in type 2 diabetic patients with nephropathy. MATERIAL AND METHODS One thousand five hundred and thirteen patients were enrolled in this randomised, placebo-controlled study of losartan (50 to 100 mg, once daily) or placebo, in addition to conventional antihypertensive treatment (calcium antagonists, diuretics, alpha- and beta-blockers, centrally acting agents) for a mean of 3.4 years. The primary outcome was the composite of doubling of baseline serum creatinine, end-stage renal disease, or death. Secondary end points included a composite of cardiovascular morbidity and mortality, proteinuria, and the progression rate of renal disease. RESULTS Baseline demographics in the two groups were similar. Three hundred and twenty-seven patients receiving losartan reached the primary end point, as compared with 359 on placebo (risk reduction = 16 per cent, p = 0.02). Losartan reduced the incidence of doubling of serum creatinine (risk reduction = 25 per cent, p = 0.006) and end-stage renal disease (risk reduction = 28 per cent, p = 0.002), but had no effect on death. Benefits exceeded that attributable to changes in blood pressure. The composite of cardiovascular morbidity and mortality was similar in the two groups, except hospitalisation for heart failure, which was reduced with losartan (risk reduction = 32 per cent, p = 0.005). Proteinuria declined by 35 per cent with losartan (p < 0.001). DISCUSSION Losartan conferred significant renal benefits in type 2 diabetic patients with nephropathy and was generally well tolerated.