The Effect of Fibrates on Kidney Function and Chronic Kidney Disease Progression: Protocol for a Systematic Review

Background/Objectives: Fibrates reduce cardiovascular risk in the general population and in patients with chronic kidney disease (CKD). Although, they are commonly used as second-line agents in addition to statins for hypertriglyceridemia, their use in CKD is limited due to a decrease of glomerular filtration rate (GFR) at treatment initiation. This change in GFR is reversible with fibrate discontinuation. Importantly, randomised control trials with fibrate treatment have demonstrated reduction in proteinuria and benefit for microvascular diabetic complications. In addition, a number of experimental studies have shown nephroprotective effects with fibrates through attenuation of renal fibrosis and inflammation. Thus, the effect of fibrates on renal outcomes remains undetermined. The objective of this systematic review is to summarize the evidence from randomised controlled studies and provide pooled estimates on the effect of fibrates on short- and long-term renal outcomes. Methods/Design: The study will be contacted according to the Cochrane Collaboration principles for Systematic reviews. We will include randomised trials comparing fibrate to placebo or studies comparing the addition of fibrate on statin versus statin alone and reporting on the short- and long-term effects on renal function, CKD progression and proteinuria. We will examine studies including patients with established CKD and those studies including patients at risk of developing CKD, separately. A comprehensive summary of the evidence will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data from included studies suitable for metanalysis will be analyses accordingly to provide quantitative estimates using a random effects model. The Cochrane Collaboration tool for assessing the risk of bias in randomized clinical trials will be utilised. The quality of the evidence from included studies will be addressed descriptively using GRADE (Grading of Recommendations, Assessment, Development and Evaluations).Discussion: The results of this systematic review will be informative for clinicians. A summary of high-level evidence with robust estimates of the effect of fibrates on safety and renal outcomes may be used to inform clinical practice guideline development for dyslipidaemias and primary and secondary prevention of CVD. Systematic review registration: PROSPERO CRD42020187764