Analysis of Metabolic Parameters as Predictors of Risk in the RENAAL Study
- Gerald B. Appel, MD1,
- Jai Radhakrishnan, MD1,
- Morrell M. Avram, MD2,
- Ralph A. DeFronzo, MD3,
- Fernando Escobar-Jimenez, MD4,
- M.M. Campos, MD4,
- Ellen Burgess, MD5,
- Darcy A. Hille, MS, EMBA6,
- Tania Z. Dickson, PHD6,
- Shahnaz Shahinfar, MD6,
- Barry M. Brenner, MD7 and
- for the RENAAL Study Investigators
- 1Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
- 2Division of Nephrology, Long Island College Hospital, Brooklyn, New York
- 3Diabetes Division, University of Texas Health Science Center, San Antonio, Texas
- 4Hospital Clinico San Cecilio Endocrine Service, Granada, Spain
- 5Hypertension Research Clinic, University of Calgary, Calgary, Canada
- 6Merck Research Laboratories, Blue Bell, Pennsylvania
- 7Renal 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 (HbA1c) 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 cholesterol were also associated with increased risk of developing ESRD.
CONCLUSIONS—Overall, losartan was well tolerated by patients with type 2 diabetes and nephropathy and was associated with a favorable effect on the metabolic profile of this population.
- AIIA, angiotensin II receptor antagonist
- ESRD, end-stage renal disease
- Lp(a), lipoprotein a
- RAAS, renin-angiotensin-aldosterone system
- RENAAL, Reduction of End Points in Type 2 Diabetes With the Angiotensin II Antagonist Losartan
Footnotes
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Address correspondence and reprint requests to Gerald B. Appel, MD, Division of Nephrology, Department of Medicine, Columbia College of Physicians and Surgeons, 622 W. 168th St., Room 4124, New York, NY 10032.
Received for publication 3 October 2002 and accepted in revised form 6 December 2003.
G.B.A. has been on an advisory panel for and has received honoraria for speaking engagements and grant/research support from Merck. M.M.A. has been on an advisory panel for Continuum Health Partners and has received grant/research support from the National Kidney Foundation of New York/New Jersey, the Nephrology Foundation of Brooklyn, Abbott, Amgen, and The New York Community Trust, Korda Fund. E.B. has been on advisory panels for AstraZeneca, Abbott, and Merck; has received honoraria for speaking engagements from Merck, Bristol-Myers Squibb, AstraZeneca, and Abbott; and has received grant/research support from Pfizer, Pharmacia, Merck, and Servier. B.M.B. has been on advisory panels for Merck, Amgen, and Genzyme and has received honoraria from Merck, Curagen, Bristol-Myers Squibb, Amgen, Aventis, and Genzyme.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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