Efficacy of febuxostat in hyperuricemic patients with mild-to-moderate chronic kidney disease

Abstract

Background:To investigate the efficacy of febuxostat in hyperuricemic patients with chronic kidney disease (CKD), relevant randomized clinical trials (RCTs) were analyzed.Methods:We used PubMed, Medline, ISI Web of Science, CBMdisc, and Cochrane Library databases to conduct a systematic literature research. A fixed-effects model was used to evaluate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). We conducted subgroup analysis, sensitivity analysis, and analyzed publication bias, to comprehensively estimate the renoprotective effects of febuxostat in hyperuricemic patients with CKD.Results:Among 296 retrieved studies, 5 relevant RCTs were included in the meta-analysis. The result showed that serum estimated glomerular filtration rate (eGFR) was improved after febuxostat treatment in hyperuricemic patients with CKD, with an SMD (95% CI) of 0.24 [−0.17 to 0.43] and P = .67 (fixed-effects model). No heterogeneity was observed across studies (I2 = 0% and P = .67). Subgroup analysis suggested that treatment-related reductions in serum eGFR levels were not related to drug doses, intervention times, or region.Conclusions:The present meta-analysis suggests that febuxostat may slow the progression of mild-to-moderate CKD. Given the limited number of included studies, additional large sample-size RCTs are required to determine the long-term renoprotective effects of febuxostat in hyperuricemic patients with CKD.

Hyperuricemia, the heart, and the kidneys – to treat or not to treat?

“…A study published recently by Vargas-Santos et al showed that allopurinol initiation of at least 300 mg/ day in newly diagnosed gout was associated with a lower risk of renal function decline [82]. Similar data were also published regarding the use of febuxostat, with additional effects on lowering blood pressure, while some researchers witnessed no effect of febuxostat on eGFR in CKD stage 3 patients with asymptomatic hyperuricemia [63,[83][84][85][86][87][88]. Others showed that allopurinol is associated with a reduction of serum creatinine, with no effect on eGFR [5].…”

“…A head to head comparison (allopurinol vs. febuxostat) described higher efficacy of febuxostat to reach target values of SUA than allopurinol in six months and has also shown an increase in eGFR, while they observed a decline of eGFR in the allopurinol group [85]. All meta-analyses concluded that currently there is insufficient evidence to support the use of ULT for treatment of CKD progression [15,83]. However, a recent study showed that CKD patients on febuxostat followed for approximately 4.5 years had a significantly slower renal disease progression than patients on allopurinol or conventional CKD treatment regardless of potent cofounders.…”

Febuxostat and Cardiovascular Events: A Systematic Review and Meta-Analysis

“…Twelve systematic reviews or meta-analysis have been published about SU-lowering therapy and gout or hyperuricemia. Six evaluated the efficacy of medications with no mention of cardiovascular events [8, 11–15], three evaluated their renoprotective effects [16–18], one evaluated the effect of SU-lowering therapy on cardiovascular prevention [7], and one evaluated the effect of SU-lowering therapy on the effects on blood pressure [19]. Only one meta-analysis [20] evaluated the cardiovascular events of febuxostat and found no excess events; however, this study did not include CARES, only searched in one database to identify cardiovascular events as adverse events, and only included four studies.…”

Research Advances in the Mechanisms of Hyperuricemia-Induced Renal Injury

“…Another cohort study, which lasted for more than 25 years and enrolled 177,570 patients, showed an independent association between high UA levels and end-stage renal diseases (ESRDs) [ 16 ]. Hyperuricemia is now considered an independent risk factor for the occurrence and development of diabetic nephropathy (DN) [ 17 , 18 ], acute kidney injury (AKI) [ 2 , 12 , 13 ], chronic kidney disease (CKD) [ 10 , 11 ], and ESRD [ 16 ]. However, inconsistent results had been reported regarding the role of UA in the progression of CKD and there were insufficient evidences to suggest lowering UA therapy to prevent the progression of CKD [ 19 – 23 ].…”