Background

Asia is predicted to have the largest population of patients with diabetes who are at high risk for renal disease. In the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study, approximately 17% of 1,513 type 2 diabetic patients with clinical proteinuria were Asians.

Objective

To examine the response to treatment with losartan and the baseline predictors of risk of renal end points in the Asian diabetic nephropathy population of the RENAAL study.

Study design

Double-blind, randomized, placebo-controlled

Methods

Losartan 50 mg vs. PlaceboAll patients received conventional antihypertensive therapy.

• After four weeks, the dose of losartan was increased to 100 mg if the target blood pressure (<140/90 mm Hg) was not achieved.

• After an additional eight weeks, antihypertensive agents (except angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists) were added or their doses increased to achieve the target blood pressure.

Patient characteristics

252 Asian patients (aged 31-70 years) with type 2 diabetic nephropathy (presence, on two occasions, of urinary albumin-to-creatinine ratio from first morning specimen 300 mg/g or rate of urinary protein excretion of ³0.5 g/day) and serum creatinine values between 1.3 and 3.0 mg/dl, with a lower limit of 1.5 mg/dl for male patients weighing >60 kg.

Duration

Mean follow-up = 3.2 years

Study outcomes

Primary endpoint
Time to the first event of composite endpoint of a doubling of serum creatinine (DsCr), end stage renal disease (ESRD) or death.

Secondary endpoint
A composite endpoint of myocardial infarction, stroke, first hospitalization for heart failure or unstable angina pectoris, coronary or peripheral vascularization or cardiovascular death.

Results

Treatment effect of losartan in the RENAAL Asian population

• Losartan significantly reduced the risk for the primary composite endpoint in the RENAAL Asian population by 35% as compared to placebo.

• The risk of renal outcomes of ESRD or DsCr was 36% lower with losartan compared to placebo.

• A significant 47% reduction in the level of proteinuria was obtained with losartan as compared to placebo.

• The rate of decrease in renal function was reduced by 30.7% with losartan as compared to placebo.

• Overall discontinuations in the study were lower in the losartan group (28%) than in the placebo group (43%).

Risk predictors for renal outcomes in the RENAAL Asian population

• The strongest baseline predictors of renal risk were proteinuria, serum albumin, serum calcium, hemoglobin, lipoprotein (a), serum creatinine and estimated glomerular filtration rate.

• Baseline proteinuria and hemoglobin were strong predictors of risk for both the primary composite endpoint (DsCr, ESRD or death) and the renal composite endpoint (DsCr or ESRD) and ESRD alone.

• The additional baseline variables significantly associated with the risk of ESRD were serum calcium, younger age (per 10 years) and serum creatinine.

Conclusion

• Losartan significantly reduced the risk of developing the primary composite end point of DsCr, ESRD, and all-cause mortality in Asian patients with type 2 diabetes and nephropathy.

• Losartan reduced proteinuria and the progression of renal disease and was well tolerated.

• In the Asian population of the RENAAL study, baseline proteinuria and hemoglobin were significant predictors of risk for the renal endpoints.

Diabetes Care 2004; 27: 874-879

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