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Renin Angiotensin Aldosterone System Blockade and Renal Disease in Patients With Type 2 Diabetes

An Asian perspective from the RENAAL study

¹ Department of Medicine and Therapeutics, The Chinese University Hong Kong, The Prince of Wales Hospital, Hong Kong, China
² Department of Medicine, The Hong Kong University, Queen Mary Hospital, Hong Kong, China
³ University Malaya Medical Centre, Kuala Lumpur, Malaysia
⁴ Singapore General Hospital, Singapore
⁵ Hospital Kuala Lumpur, Kuala Lumpur, Malaysia
⁶ Merck Research Laboratories, West Point, Pennsylvania
⁷ Department of Medicine, Austin and Repatriation Centre, Medical Centre, University of Melbourne, Melbourne, Australia
⁸ Renal Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
⁹ Tokai University School of Medicine, Tokai, Japan

Address correspondence and reprint requests to Dr. Juliana C.N. Chan, Professor, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong. E-mail: jchan{at}cuhk.edu.hk

OBJECTIVE—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, 17% of patients were Asians. In this subgroup analysis, we examined the characteristics, response, and adherence to treatment of the Asian population, as well as their baseline predictors of risk of renal end points.

RESEARCH DESIGN AND METHODS—A total of 252 Asian patients were enrolled in the RENAAL study, which compared losartan (50 mg titrated to 100 mg) to placebo in addition to conventional antihypertensive medications in type 2 diabetic patients with nephropathy. Mean follow-up was 3.2 years. The effect of losartan therapy on renal and cardiovascular outcomes was examined, and baseline predictors of risk were determined using a Cox proportional hazards model with prespecified baseline covariates.

RESULTS—Losartan reduced the risk of the primary composite end point composed of a doubling of serum creatinine, end-stage renal disease, or all-cause mortality in Asian patients by 35% (P = 0.02). No difference between losartan and placebo was observed for the cardiovascular composite outcomes. Losartan reduced the level of proteinuria by 47% (P < 0.001) and rate of decrease in renal function by 31% (0.0074). Discontinuations were lower in the losartan-treated patients. The strongest baseline predictors of risk of renal end points were proteinuria (hazard ratio 1.42, P < 0.0001) and low Hb (0.81, P < 0.0001).

CONCLUSIONS—In this subgroup analysis of the RENAAL study, losartan conferred significant renal benefits and was well tolerated in Asian patients with type 2 diabetes and clinical nephropathy. Baseline proteinuria and low Hb were strong predictors of risk of renal outcomes.

Abbreviations: AII, angiotensin II • DsCr, doubling of serum creatinine • ESRD, end-stage renal disease • RENAAL, Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan

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