Analysis of Metabolic Parameters as Predictors of Risk in the RENAAL Study

Analysis of Metabolic Parameters as Predictors of Risk in the RENAAL Study Gerald B. Appel , MD 1 , Jai Radhakrishnan , MD 1 , Morrell M. Avram , MD 2 , Ralph A. DeFronzo , MD 3 , Fernando Escobar-Jimenez , MD 4 , M.M. Campos , MD 4 , Ellen Burgess , MD 5 , Darcy A. Hille , MS, EMBA 6 , Tania Z. Dickson , PHD 6 , Shahnaz Shahinfar , MD 6 , Barry M. Brenner , MD 7 and for the RENAAL Study Investigators 1 Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 2 Division of Nephrology, Long Island College Hospital, Brooklyn, New York 3 Diabetes Division, University of Texas Health Science Center, San Antonio, Texas 4 Hospital Clinico San Cecilio Endocrine Service, Granada, Spain 5 Hypertension Research Clinic, University of Calgary, Calgary, Canada 6 Merck Research Laboratories, Blue Bell, Pennsylvania 7 Renal Division, Brigham and Women’s Hospital, Boston, Massachusetts Abstract OBJECTIVE —Metabolic factors such as glycemic control, hyperlipidemia, and hyperkalemia are important considerations in the treatment of patients with type 2 diabetes and nephropathy. In the RENAAL (Reduction of End Points in Type 2 Diabetes With the Angiotensin II Antagonist Losartan) study, losartan reduced renal outcomes in the patient population. This post hoc analysis of the RENAAL study reports the effects of losartan on selected metabolic parameters and assesses the relationship between baseline values of metabolic parameters and the primary composite end point or end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS —Glycemic control (HbA 1c ) and serum lipid, uric acid, and potassium levels were compared between the losartan and placebo groups over time, and baseline levels were correlated with the risk of reaching the primary composite end point (doubling of serum creatinine, ESRD, or death) or ESRD alone. RESULTS —Losartan did not adversely affect glycemic control or serum lipid levels. Losartan-treated patients had lower total (227.4 vs. 195.4 mg/dl) and LDL (142.2 vs. 111.7 mg/dl) cholesterol. Losartan was associated with a mean increase of up to 0.3 mEq/l in serum potassium levels; however, the rate of hyperkalemia-related discontinuation was similar between the placebo and losartan groups. Univariate analysis revealed that baseline total and LDL cholesterol and triglyceride levels were associated with increased risk of developing the primary composite end point. Similarly, total and LDL cholester