Effects of Losartan on Renal and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Nephropathy - RENAAL


Effects of Losartan on Renal and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Nephropathy.


ACE inhibition slows the progression of renal disease in type 1 diabetics. This study was designed to assess the effect of the angiotensin-II receptor blocker losartan in type 2 diabetics with nephropathy on the progression of renal disease and death.

Study Design

Study Design:

Patients Enrolled: 1513

Primary Endpoints:

The time to first event of a composite of doubling of the serum creatinine, end-stage renal disease or death.

Secondary Endpoints:

The composite morbidity or mortality from cardiovascular causes including MI, stroke, hospitalization for angina or CHF, coronary or peripheral revascularization or death. The components of the composite primary and secondary endpoints were also prespecified for analysis.

Drug/Procedures Used:

1513 adult-onset diabetics with nephropathy (urinary albumin/creatinine ratio >300 or at least 0.5 g/day of protein and serum creatinine 1.3-3 mg/dL) were stratified by the degree of proteinuria and randomized to placebo vs. 50mg of losartan along with non-ACE conventional anti-hypertensive drugs. Losartan or placebo was increased to 100mg followed by an increase in non-ACE drugs to decrease the BP to <140/90 mm Hg.

Principal Findings:

The average age was 60 years, 62% were male, BMI was 29.5 kg/m2, BP 152/82 mm Hg, 28% CVD including 8% amputations, mean serum creatinine was 1.9 mg/dL and glycosylated Hgb 8.5%. Calcium channel blockers were used by about 70% of subjects in both groups at baseline and during the study in 77.9% on losartan and 81.1% placebo. A dihydropyridine was the calcium channel blocker in about 55% of subjects at baseline and 62% during the study. During an average follow-up of 3.4 years, losartan reduced the combined primary renal end point by 16% (p=0.02), the incidence of doubling of serum creatinine by 25% (p=0.006) and end-stage renal disease by 28% (p=0.002) with no effect on mortality. The benefits exceeded changes attributable to blood pressure. There was no difference in the composite cardiovascular endpoints but there was a 32% (p=0.005) reduction in first hospitalization for CHF, and a 35% reduction in proteinuria with losartan (p<0.001) compared to placebo.

Losartan conferred significant renal benefits in patients with type 2 diabetes and nephropathy and was well tolerated.


The observed decrease in progression of renal failure corresponds to an average 2-year delay in need for dialysis or transplantation.


1. Brenner BM, Cooper ME, de Zeeuw D, et al. for the RENAAL Study Investigators. N Engl J Med 2001;345:861-9.

Keywords: Losartan, Angiotensin Receptor Antagonists, Dihydropyridines, Follow-Up Studies, Kidney Failure, Chronic, Diabetes Mellitus, Type 2, Blood Pressure, Proteinuria, Creatinine, Calcium Channel Blockers, Renal Dialysis, Body Mass Index, Hospitalization

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