Effects of Fibrates in Kidney Disease

• Published in: Journal of the American College of Cardiology 2012-11, Vol.60 (20), p.2061-2071
• Main Authors: Jun, Min, BSc(Hons), MSc(ClinEpi), Zhu, Bin, MD, PhD, Tonelli, Marcello, MD, PhD, Jardine, Meg J., MBBS, PhD, Patel, Anushka, MBBS, PhD, Neal, Bruce, MB, ChB, PhD, Liyanage, Thaminda, MBBS, Keech, Anthony, MBBS, MSc (Epid), Cass, Alan, MBBS, PhD, Perkovic, Vlado, MBBS, PhD
• Format: Article
• Language: English
• Subjects: Age; Cardiology; Cardiovascular; Cardiovascular disease; Cholesterol; chronic kidney disease; Clinical outcomes; Clinical trials; Confidence intervals; Diabetes; Drug therapy; fibrate; Heart attacks; Internal Medicine; Intervention; Kidney diseases; Lipids; Lipoproteins; meta-analysis; Mortality; Population; Studies; systematic review; triglyceride cholesterol
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2012.07.049

Objectives The purpose of this systematic review and meta-analysis was to determine the efficacy and safety of fibrate therapy in the chronic kidney disease (CKD) population. Background Fibrate therapy produces modest cardiovascular benefits in people at elevated cardiovascular risk. There is limited evidence about the clinical benefits and safety of fibrate therapy in the CKD population. Methods MEDLINE, EMBASE, and the Cochrane Library were systematically searched (1950 to January 2012) for prospective randomized controlled trials assessing the effects of fibrate therapy compared with placebo in people with CKD or on kidney-related outcomes were included. Results Ten studies including 16,869 participants were identified. In patients with mild-to-moderate CKD (estimated glomerular filtration rate [eGFR] ≤60 ml/min/1.73 m2 ), fibrates improved lipid profiles (lowered total cholesterol [−0.32 mmol/l, p = 0.05] and triglyceride levels [−0.56 mmol/l, p = 0.03] but not low-density lipoprotein cholesterol [−0.01 mmol/l, p = 0.83]; increased high-density lipoprotein cholesterol [0.06 mmol/l, p = 0.001]). In people with diabetes, fibrates reduced the risk of albuminuria progression (relative risk [RR]: 0.86; 95% confidence interval [CI]: 0.76 to 0.98; p = 0.02). Serum creatinine was elevated by fibrate therapy (33 μmol/l, p < 0.001), calculated GFR was reduced (−2.67 ml/min/1.73 m2 , p = 0.01) but there was no detectable effect on the risk of end-stage kidney disease (RR: 0.85; 95% CI: 0.49 to 1.49; p = 0.575). In patients with eGFR of 30 to 59.9 ml/min/1.73 m2 , fibrates reduced the risk of major cardiovascular events (RR: 0.70; 95% CI: 0.54 to 0.89; p = 0.004) and cardiovascular death (RR: 0.60; 95% CI: 0.38 to 0.96; p = 0.03) but not all-cause mortality. There were no clear safety concerns specific to people with CKD but available data were limited. Conclusions Fibrates improve lipid profiles and prevent cardiovascular events in people with CKD. They reduce albuminuria and reversibly increase serum creatinine but the effects on major kidney outcomes remain unknown. These results suggest that fibrates have a place in reducing cardiovascular risk in people with mild-to-moderate CKD.