Christian G. Rabbat, MD
In patients with type 2 diabetes mellitus and nephropathy, what is the renoprotective effect of the angiotensin-II–receptor antagonist (ARA) losartan?
Randomized (allocation concealed*), blinded (clinicians, patients, outcome assessors, and statisticians),* placebo-controlled trial with mean follow-up of 3.4 years (the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan [RENAAL] Study).
250 centers worldwide.
1513 patients between 31 and 70 years of age (mean age 60 y, 63% men) who had type 2 diabetes and nephropathy defined as a urinary albumin-to-creatinine ratio ≥ 300 mg/g and a serum creatinine level between 115 and 265 µmol/L (≥ 133 µmol/L for men weighing > 60 kg). Exclusion criteria included type 1 diabetes and nondiabetic renal disease. Follow-up was 99.8%.
After stratification by baseline level of proteinuria, patients were allocated to receive losartan, 50 to 100 mg/d (n = 751), or placebo (n = 762). Conventional antihypertensive therapy (excluding angiotensin-I–converting enzyme inhibitors and ARAs) was adjusted to target a systolic and diastolic blood pressure < 140 and < 90 mm Hg, respectively.
The primary outcome was the composite of a doubling of the baseline serum creatinine level, end-stage renal disease (ESRD), or death. The secondary outcome was the composite of cardiovascular morbidity or mortality.
Analysis was by intention to treat. Losartan reduced the risk for the primary composite outcome (unadjusted P = 0.02; P = 0.03 after adjustment for blood pressure), doubling of the baseline serum creatinine level (unadjusted P = 0.006), and ESRD (unadjusted P = 0.002) more than did placebo (Table). However, losartan and placebo did not differ for incidence of death (unadjusted P = 0.88) (Table) or the secondary composite outcome of cardiovascular morbidity or mortality (P = 0.26).
Losartan was renoprotective in patients with type 2 diabetes mellitus and nephropathy. This effect was beyond that attributable to blood pressure control.
Losartan vs placebo for type 2 diabetes and nephropathy at mean 3.4 years†
†Abbreviations defined in Glossary.
‡Based on Cox regression model.
§Composite outcome = doubling of baseline serum creatinine level, end-stage renal disease, or death.
Christian G. Rabbat. Losartan was renoprotective in diabetic nephropathy independent of its effect on blood pressure. Ann Intern Med. 2002;136:84. doi: 10.7326/ACPJC-2002-136-3-084
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Published: Ann Intern Med. 2002;136(3):84.
Cardiology, Coronary Risk Factors, Diabetes, Diabetic Nephropathy, Endocrine and Metabolism.
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