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The losartan renal protection study — rationale, study design and baseline characteristics of RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan)
Barry M Brenner
Renal Division, Brigham and Women's Hospital, Boston, MA, USA, bmbrenner@ bics.bwh.harvard.edu
Mark E Cooper
Department of Medicine, University of Melbourne, Victoria, Australia
Dick de Zeeuw
Department of Clinical Pharmacology, University of Groningen, The Netherlands
Jean-Pierre Grunfeld
Service Nephrologie, Groupe Hospitalier, Necker-Enfants Maldes, Paris, France
William F Keane
Department of Medicine, Hennepin County Medical Center, Minneapolis, MN, USA
Kiyoshi Kurokawa
Dean's Office, Tokai University School of Medicine, Kanagawa, Japan
Janet B McGill
Department of Medicine, Washington University, St Louis, MO, USA
William E Mitch
Renal Division, Emory University, Atlanta, GA, USA
Hans Henrik Parving
Steno Diabetes Center, Gentofte, Denmark
Guiseppe Remuzzi
Laboratori Negri Bergamo, Instituto Di Ricerche Farmacologiche Mario Negri, Bergamo, Italy
Arthur B Ribeiro
Nephrology Division, Escola Paulista de Medicina, Sao Paulo, Brazil
Mark D Schluchter
Division of Clinical Epidemiology, Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA
Duane Snavely
Merck Research Laboratories, Blue Bell, PA, USA
Zhongxin Zhang
Merck Research Laboratories, Blue Bell, PA, USA
Roger Simpson
Merck Research Laboratories, Blue Bell, PA, USA
Denise Ramjit
Merck Research Laboratories, Blue Bell, PA, USA
Shahnaz Shahinfar
Merck Research Laboratories, Blue Bell, PA, USA
RENAAL Study Investigators
The RENAAL Study is a double-blind, placebo-controlled trial to evaluate the renal protective effects of losartan in Type 2 diabetic patients with nephropathy. The study has enrolled 1513 patients and is expected to continue for 3.5 years after the last patient has been entered. Eligible patients must have a urinary albumin:creatinine ratio of at least 300 mg/g and serum creatinine between 1.3 to 3.0 mg/dL. Eligible hypertensive or normotensive patients are randomised to receive either losartan or placebo, in addition to their existing antihypertensive therapy. Medications that block angiotensin production or action, are excluded. The primary endpoint is a composite of the time to first event of doubling of serum creatinine, end-stage renal disease, or death; secondary endpoints include cardiovascular events, progression of renal disease, and changes in proteinuria; tertiary endpoints include quality of life, healthcare resource utilisation, and amputations. Patients include Caucasians (48.6%), Blacks (15.2%), Asians (16.7%), and Hispanics (18.2%). Baseline urinary albumin:creatinine ratio and serum creatinine levels average 1867 mg/g and 1.9 mg/dL, respectively. Mean systolic and diastolic blood pressures are 153 and 82 mmHg, respectively. RENAAL will document whether blockade of the AII receptor with losartan produces clinical benefits in patients with Type 2 diabetes and nephropathy.
Key Words: end-stage renal disease • non-insulin dependent diabetes mellitus • losartan • angiotensin II receptor antagonist • creatinine clearance • proteinuria
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DOI: 10.3317/jraas.2000.062
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