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Effects of fibrates in kidney disease: a systematic review and meta-analysis
Min Jun1, Bin Zhu, Marcello Tonelli
1George Institute for Global Health, the University of Sydney, Sydney, New South Wales, Australia.
Insights
Fibrates improve lipid profiles and cardiovascular health in chronic kidney disease (CKD) patients. While they increase creatinine, they do not appear to worsen major kidney outcomes.
Area of Science:
- Nephrology
- Cardiology
- Pharmacology
Background:
- Fibrate therapy offers cardiovascular benefits in high-risk individuals.
- Evidence on fibrate efficacy and safety in chronic kidney disease (CKD) populations is limited.
Purpose of the Study:
- To systematically review and meta-analyze the efficacy and safety of fibrate therapy in patients with CKD.
Main Methods:
- Systematic search of MEDLINE, EMBASE, and Cochrane Library (1950-2012).
- Inclusion of prospective randomized controlled trials comparing fibrates to placebo in CKD patients.
- Analysis of kidney-related and cardiovascular outcomes.
Main Results:
- Fibrates improved lipid profiles (total cholesterol, triglycerides, HDL) in mild-to-moderate CKD.
- Reduced albuminuria progression in diabetic patients.
- Temporarily increased serum creatinine and reduced calculated GFR, without affecting end-stage kidney disease risk.
- Decreased major cardiovascular events and cardiovascular death in patients with eGFR 30-59.9 ml/min/1.73 m(2).
Conclusions:
- Fibrates are effective in improving lipid profiles and reducing cardiovascular events in mild-to-moderate CKD.
- Albuminuria is reduced, and serum creatinine is reversibly increased.
- Long-term effects on major kidney outcomes require further investigation.
- Fibrates may play a role in cardiovascular risk reduction for CKD patients.
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 m(2)), 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 m(2), 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 m(2), 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.
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