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(Circulation. 2005;112:171-178.)
© 2005 American Heart Association, Inc.

Coronary Heart Disease

Effect of Pravastatin on Rate of Kidney Function Loss in People With or at Risk for Coronary Disease

Marcello Tonelli, MD, SM; Chris Isles, MD; Timothy Craven, MSPH; Andrew Tonkin, MD; Marc A. Pfeffer, MD, PhD; James Shepherd, MD; Frank M. Sacks, MD; Curt Furberg, MD; Stuart M. Cobbe, MD; John Simes, MD, MSc; Malcolm West, MD; Chris Packard, MD; Gary C. Curhan, MD, ScD

From the Division of Nephrology and Division of Critical Care Medicine, University of Alberta, and Institute of Health Economics, Edmonton, Alberta, Canada (M.T.); Department of Medicine, Dumfries and Galloway Royal Infirmary, Dumfries, Scotland, UK (C.I.); Wake Forest University School of Medicine, Winston-Salem, NC (T.C., C.F.); Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia (A.T.); Cardiovascular Division, Brigham and Women’s Hospital, Boston, Mass (M.A.P.); University of Glasgow, Glasgow, Scotland, UK (J.S., S.M.C.); Department of Nutrition, Harvard School of Public Health, Boston, Mass (F.M.S.); University of Sydney, Sydney, Australia (J.S.); Department of Medicine, University of Queensland, Brisbane, Australia (M.W.); Department of Pathological Biochemistry, Glasgow Royal Infirmary, Glasgow, Scotland, UK (C.P.); and Department of Epidemiology, Harvard School of Public Health, and Renal Division and Channing Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (G.C.C.).

Correspondence to Dr Marcello Tonelli, Division of Nephrology, University of Alberta, 7-129 Clinical Science Bldg, 8440 112 St, Edmonton, Alberta T6G 2G3, Canada. E-mail mtonelli{at}ualberta.ca

Received October 28, 2004; revision received March 3, 2005; accepted March 16, 2005.

Background— Limited data suggest that HMG-CoA reductase inhibitors (statins) reduce rates of kidney function loss. We performed this analysis to determine whether pravastatin reduced the rate of kidney function loss over 5 years in people with or at high risk for coronary disease.

Methods and Results— This was a post hoc subgroup analysis of data from 3 randomized double-blind controlled trials comparing pravastatin 40 mg/d and placebo in subjects with a previous acute coronary syndrome or who were at high cardiovascular risk. The primary outcome was the rate of change in estimated glomerular filtration rate (GFR; in mL/min per 1.73 m²/y). The Modified Diet and Renal Disease Study (MDRD) and Cockcroft-Gault equations were used to estimate GFR. We studied 18 569 participants, 3402 (18.3%) of whom had moderate chronic kidney disease as defined by an estimated GFR of 30 to 59.9 mL/min per 1.73 m² body surface area. In subjects with moderate chronic kidney disease at baseline, pravastatin reduced the adjusted rate of kidney function loss by 34%, although the absolute reduction in the rate of loss was small (0.22 mL/min per 1.73 m²/y by MDRD-GFR; 95% CI, 0.07 to 0.37). Pravastatin did not reduce the frequency of 25% decreases in kidney function in this group when MDRD-GFR was used to estimate GFR (relative risk [RR], 0.84; 95% CI, 0.66 to 1.06). When all 18 569 subjects were considered, pravastatin reduced the adjusted rate of kidney function loss by 8% (0.08 mL/min per 1.73 m²/y by MDRD-GFR; 95% CI, 0.01 to 0.15) and the risk of acute renal failure (RR, 0.60; 95% CI, 0.41 to 0.86) but did not significantly reduce the frequency of a 25% decline in kidney function by MDRD-GFR (RR, 0.94; 95% CI, 0.88 to 1.01).

Conclusions— Pravastatin modestly reduced the rate of kidney function loss in people with or at risk for cardiovascular disease. However, the primary indication for the use of statins in people with or at risk for coronary events remains the reduction in mortality that results from their use.

Key Words: cholesterol • statins • kidney

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