Renin Angiotensin Aldosterone System Blockade and Renal Disease in Patients With Type 2 Diabetes
An Asian perspective from the RENAAL study
- Juliana C.N. Chan, MD, FRCP1,
- Nelson M.S. Wat, MBBS, MRCP2,
- Wing-Yee So, MBBS, MRCP1,
- Karen S.L. Lam, MD, FRCP2,
- Chin-Teong Chua, MRCP, FRCP3,
- Kok-Seng Wong, MMED, MRCP, FAMS4,
- Zaki Morad, MRCP, FRCP5,
- Tania Z. Dickson, PHD6,
- Darcy Hille, EMBA6,
- Zhongxin Zhang, PHD6,
- Mark E. Cooper, MBBS, MD, PHD, FRACP7,
- Shahnaz Shahinfar, MD6,
- Barry M. Brenner, MD8,
- Kiyoshi Kurokawa, MD9 and
- on behalf of the Asian RENAAL Study Investigators
- 1Department of Medicine and Therapeutics, The Chinese University Hong Kong, The Prince of Wales Hospital, Hong Kong, China
- 2Department of Medicine, The Hong Kong University, Queen Mary Hospital, Hong Kong, China
- 3University Malaya Medical Centre, Kuala Lumpur, Malaysia
- 4Singapore General Hospital, Singapore
- 5Hospital Kuala Lumpur, Kuala Lumpur, Malaysia
- 6Merck Research Laboratories, West Point, Pennsylvania
- 7Department of Medicine, Austin and Repatriation Centre, Medical Centre, University of Melbourne, Melbourne, Australia
- 8Renal Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
- 9Tokai 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
Abstract
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.
- 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
Footnotes
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Z.M. is a member of the Asian Advisory Board for Merck Sharp & Dohme, which manufactures losartan, the drug used in this study; Z.M. received no honoraria. M.C. is a member of the RENAAL Steering Committee and has received honoraria from Merck. K.K. has received honoraria from Merck-Banyu for lectures related to RENAAL.
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- Accepted January 8, 2004.
- Received August 29, 2003.
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