Effect of gemfibrozil on change in renal function in men with moderate chronic renal insufficiency and coronary disease

Background: Limited data suggest that low levels of serum high-density lipoprotein cholesterol (HDL-C) and high levels of triglyceride-rich lipoproteins may be associated with more rapid rates of kidney function loss in individuals with chronic renal insufficiency (CRI). Although fibric acid derivatives increase serum HDL-C levels and decrease triglyceride levels, their effects on renal function are largely unknown. We conducted this study to determine whether gemfibrozil reduced rates of renal function loss in people with moderate CRI. Methods: This was a post hoc subgroup analysis in the Veterans Affairs High-Density Lipoprotein Intervention Trial, a randomized double-blind trial of gemfibrozil versus placebo in 2,531 men with coronary disease, HDL-C levels of 40 mg/dL or less (≤1.0 mmol/L), low-density lipoprotein cholesterol levels of 140 mg/dL or less (≤3.6 mmol/L), and a range of triglyceride values. Moderate CRI is defined as estimated glomerular filtration rate (GFR) of 30 to 59.9 mL/min/1.73 m ² at baseline. Multivariate regression was used to calculate rates of decline in estimated GFR for individuals administered gemfibrozil or placebo, controlling for prospectively determined potential confounders. Results: Change in renal function could be calculated in 1,981 individuals, of whom 399 individuals (20.2%) were eligible for inclusion. Among 399 study subjects, the rate of change in renal function in the gemfibrozil group during a median of 61 months was not significantly different from that in the placebo group (0.49 mL/min/1.73 m ²/y faster; 95% confidence interval, 0.09 slower to 1.09 faster; P = 0.10). No clinically relevant effect of gemfibrozil on renal function was observed in groups defined by baseline lipid levels, kidney function, diabetic status, or other components of the metabolic syndrome. The incidence of transient (10% versus 4%; P = 0.01), but not sustained (9% versus 4%; P = 0.07), increases in serum creatinine levels of 0.5 mg/dL or greater (≥44 μmol/L) was significantly greater in the gemfibrozil group. However, in 5 subjects with acute increases in serum creatinine levels, serum creatine kinase levels were significantly elevated as well, suggesting that myocyte toxicity may have been responsible. Even when these individuals were excluded, no clinically significant effect of gemfibrozil on kidney function was observed. Conclusion: Gemfibrozil does not appear to exert a clinically relevant effect on rates of kidney function loss in individuals with moderate CRI, low HDL-C levels, and concomitant coronary disease.