The Effect of Fibrates on Kidney Function: A Systematic Review and Meta-Analysis

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Background: Randomized controlled trials (RCTs) have investigated the effects of fibrates on cardiovascular events. Fibrates are known to cause an acute decline in estimated glomerular filtration rate (eGFR) but their long-term effect on kidney function is unclear. Some trials have indicated that following the acute decline fibrates improve the long-term rate of eGFR decline. We conducted a systematic review and meta-analysis to elucidate the impact of fibrates on kidney function. Methods: This review was prospectively registered on PROSPERO (CRD42023377211) and conducted according to the PRISMA 2020 guidelines. Literature searches were conducted in MEDLINE, EMBASE, CINAHL and Scopus. Inclusion criteria were RCTs in adults comparing fibrates to placebo or active comparator that reported eGFR at at least two timepoints. Screening, data extraction and risk of bias assessments were conducted in-duplicate. Random-effects, restricted maximum likelihood, inverse variance meta-analyses were used to pool treatment effects. Primary outcomes included the effect on acute change in eGFR (defined as within the first 4 months), chronic eGFR slope (defined as the eGFR slope following the acute period) and post-washout eGFR. Additional outcomes were change in albuminuria and the incidence of ESRD. Results: Fifteen (N=16,957) eligible RCTs were included. When compared to control, fibrates led to an acute decline in eGFR (MD -9.53 ml/min/1.73 m2; 95% CI -12.12 to -6.94) that was present at the end of the study period as well (MD -6.29 ml/min/1.73 m2; 95% CI -14.64 to -2.06). Based on the data available, we were unable to meta-analyze the effect of fibrates on chronic slope. However, two RCTs reported a beneficial effect of fibrates on chronic eGFR slope (-1.19 vs -2.03 ml/min/1.73 m2 per year and -0.27 vs -1.26 ml/min/1.73 m2 per year, p<0.001). Following washout, fibrates improved eGFR as compared to control (MD 3.60 ml/min/1.73 m2; 95% CI 0.02 to 7.17). Fibrates reduced albuminuria (MD -0.17 mg/g; 95% CI -0.25 to -0.10). There was no statistically significant effect on ESRD (RR 0.93; 95% CI 0.71 to 1.22). Conclusions: Fibrates cause an acute decline in eGFR and an improvement in the rate of eGFR decline thereafter. Further studies are needed to determine the long-term impact of fibrates on renal function.

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