Abstract
Aim: Fibrates have proven efficacy in cardiovascular risk reduction and are commonly used, in addition to statins, to control hypertriglyceridaemia. Their use is often limited due to reduction in glomerular filtration rate at treatment initiation. However, recent studies suggest benign changes in kidney function and improvement of proteinuria, an established early marker of microvascular disease and kidney disease progression. We summarize the evidence from existing trials and provide a summary of effects of fibrates, alone or in combination, on kidney disease progression and proteinuria. Methods and Results: Systematic review and meta-analysis of randomized, controlled trials (PROSPERO CRD42020187764). Out of 12,243 potentially eligible studies, 29 were included in qualitative and quantitative analysis, with a total of 20,176 patients. Mean creatinine increased by 1.05 (95% CI (0.63 to 1.46)) units in patients receiving fibrates vs. comparator, and this was similar in all other subgroups. eGFR showed a bigger decrease in the fibrates arm (SMD −1.99; 95% CI (−3.49 to −0.48)) when all studies were pooled together. Notably, short-term serum creatinine and eGFR changes remained constant in the long-term. Pooled estimates show that fibrates improve albuminuria progression, RR 0.86; 95% CI (0.76 to 0.98); albuminuria regression, RR 1.19; 95% CI (1.08 to 1.310). Conclusions: Fibrates improve albuminuria in patients with and without diabetes when used to treat hyperlipidaemia. The modest creatinine increase should not be a limiting factor for fibrate initiation in people with preserved renal function or mild CKD. The long-term effects on kidney disease progression warrant further study.
Highlights
Introduction published maps and institutional affilChronic kidney disease (CKD) is a common disease with increasing prevalence
Patients with CKD have a distinct lipid profile characterised by elevated triglyceride-rich lipoproteins and low high density lipoprotein (HDL) levels, which are associated with subclinical atherosclerosis, coronary artery disease and mortality [5]
Our study is in agreement with a previous meta-analysis and expands further on the effect of fibrates alone, or in combination with a statin, on kidney function and proteinuria
Summary
Introduction published maps and institutional affilChronic kidney disease (CKD) is a common disease with increasing prevalence. Patients with CKD are at increased risk of developing cardiovascular disease (CVD) which is the leading cause of death in this population [2]. CVD mortality accounts for up to 50% of deaths in patients who progress to ESKD [3]. Fibrates, which are peroxisome proliferator-activated receptor (PPAR) a-activators, are agents used for the treatment of dyslipidaemia. They lower triglyceride and low-density lipoprotein (LDL) levels, while they increase high density lipoprotein (HDL) levels [4]. Patients with CKD have a distinct lipid profile characterised by elevated triglyceride-rich lipoproteins and low HDL levels, which are associated with subclinical atherosclerosis, coronary artery disease and mortality [5]
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