Effects of Fibrates in Kidney Disease
Effects of Fibrates in Kidney Disease
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.
The burden of chronic kidney disease (CKD) is large and growing, affecting 10% to 15% of the adult population. Defined as a glomerular filtration rate (GFR) below 60 ml/min/1.73 m or the presence of other markers of kidney deterioration including albuminuria or proteinuria CKD is associated with increased risk of kidney failure and cardiovascular events. While preventing progressive kidney dysfunction is a core aspect of managing these individuals, the risk of cardiovascular disease is greatly elevated in people with CKD and is the leading cause of death in this population. Treatments that can prevent 1 or both of these adverse outcomes are therefore key to improving the long-term outcomes for this high-risk group.
Accumulating data suggest that a range of interventions that are effective at preventing cardiovascular disease in the general population are likely to be similarly efficacious in people with CKD. Recent evidence suggests that lipid lowering, antiplatelet agents, and blood pressure lowering (() prevent cardiovascular events in CKD, and the latter may also prevent progression of renal disease.
A meta-analysis of studies assessing the effects of fibrates on cardiovascular events in the broader population has reported overall benefit, with consistent evidence of greater effects for subgroups with elevated triglyceride and/or decreased HDL levels. However, no adequately powered outcome study of fibrate therapy has been reported to date specifically in the CKD population.
While dyslipidemia is a risk factor for progressive kidney disease the acute elevation of creatinine caused by fibrates has resulted in concerns about the safety of this therapy in the CKD population and there have been conflicting reports regarding the impact of fibrate therapy on kidney function.
In this systematic review, we sought to synthesize the available clinical trial evidence to better define any benefits of fibrate therapy on kidney-related outcomes and on cardiovascular events in people with CKD, as well as any adverse effects.
Abstract and Introduction
Abstract
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.
Introduction
The burden of chronic kidney disease (CKD) is large and growing, affecting 10% to 15% of the adult population. Defined as a glomerular filtration rate (GFR) below 60 ml/min/1.73 m or the presence of other markers of kidney deterioration including albuminuria or proteinuria CKD is associated with increased risk of kidney failure and cardiovascular events. While preventing progressive kidney dysfunction is a core aspect of managing these individuals, the risk of cardiovascular disease is greatly elevated in people with CKD and is the leading cause of death in this population. Treatments that can prevent 1 or both of these adverse outcomes are therefore key to improving the long-term outcomes for this high-risk group.
Accumulating data suggest that a range of interventions that are effective at preventing cardiovascular disease in the general population are likely to be similarly efficacious in people with CKD. Recent evidence suggests that lipid lowering, antiplatelet agents, and blood pressure lowering (() prevent cardiovascular events in CKD, and the latter may also prevent progression of renal disease.
A meta-analysis of studies assessing the effects of fibrates on cardiovascular events in the broader population has reported overall benefit, with consistent evidence of greater effects for subgroups with elevated triglyceride and/or decreased HDL levels. However, no adequately powered outcome study of fibrate therapy has been reported to date specifically in the CKD population.
While dyslipidemia is a risk factor for progressive kidney disease the acute elevation of creatinine caused by fibrates has resulted in concerns about the safety of this therapy in the CKD population and there have been conflicting reports regarding the impact of fibrate therapy on kidney function.
In this systematic review, we sought to synthesize the available clinical trial evidence to better define any benefits of fibrate therapy on kidney-related outcomes and on cardiovascular events in people with CKD, as well as any adverse effects.
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