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Effects of uric acid-lowering therapy in patients with chronic kidney disease: A meta-analysis.

ABSTRACT: The effects of uric acid-lowering therapy in patients with chronic kidney disease (CKD) remain uncertain. Therefore, we undertook a systematic review and meta-analysis to investigate the effects of uric acid-lowering agents on major clinical outcomes of CKD.According to the pre-specified protocol that was registered with PROSPERO (No. CRD42016038030), we searched systematically in MEDLINE, EMBASE, and the Cochrane Library for trials up to February 2016. Prospective, randomized, controlled trials assessing the effects of uric acid-lowering agents on cardiovascular and kidney outcomes in patients with CKD were included. Random-effects analytical methods were used.Sixteen eligible trials were identified, providing data for 1,211 patients with CKD, including 146 kidney failure events and 69 cardiovascular events. Uric acid-lowering therapy produced a 55% relative risk (RR) reduction (95% confidence interval [95% CI], 31-64) for kidney failure events (P < 0.001), and a 60% RR reduction (95% CI, 17-62) for cardiovascular events (P < 0.001), but had no significant effect on the risk of all-cause death (RR, 0.86; 95% CI, 0.50-1.46). The mean differences in rate of decline in the estimated glomerular filtration rate (4.10 mL/min/1.73 m2 per year slower in uric acid-lowering therapy recipients, 95% CI, 1.86-6.35) and the standardized mean differences in the change in proteinuria or albuminuria (-0.23 units of standard deviation greater in uric acid-lowering therapy recipients; 95% CI, -0.43 to -0.04) were also statistically significant.Uric acid-lowering therapy seemed to improve kidney outcomes and reduce the risk of cardiovascular events in adults with CKD.

SUBMITTER: Su X

PROVIDER: S-EPMC5667873 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Effects of uric acid-lowering therapy in patients with chronic kidney disease: A meta-analysis.

Su Xiaole X Xu Boyang B Yan Bingjuan B Qiao Xi X Wang Lihua L

PloS one 20171102 11

<h4>Background and objectives</h4>The effects of uric acid-lowering therapy in patients with chronic kidney disease (CKD) remain uncertain. Therefore, we undertook a systematic review and meta-analysis to investigate the effects of uric acid-lowering agents on major clinical outcomes of CKD.<h4>Design, setting, participants, and measurements</h4>According to the pre-specified protocol that was registered with PROSPERO (No. CRD42016038030), we searched systematically in MEDLINE, EMBASE, and the C ...[more]

PMID: 29095953

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Project description:ImportanceUric acid is a waste metabolite produced from the breakdown of purines, and elevated serum uric acid levels are associated with higher risk of hypertension, cardiovascular disease, and mortality and progression of chronic kidney disease (CKD). Treatment of hyperuricemia in patients with preexisting CKD has not been shown to improve kidney outcomes, but the associations of uric acid-lowering therapies with the development of new-onset kidney disease in patients with estimated glomerular filtration rate (eGFR) within reference range and no albuminuria is unclear.ObjectiveTo examine the association of initiating uric acid-lowering therapy with the incidence of CKD.Design, setting, and participantsThis cohort study included patients with eGFR of 60 mL/min/1.73 m2 or greater and no albuminuria treated at US Department of Veterans Affairs health care facilities from 2004 to 2019. Clinical trial emulation methods, including propensity score weighting, were used to minimize confounding. Data were analyzed from 2020 to 2022.ExposureNewly started uric acid-lowering therapy.Main outcomes and measuresThe main outcomes were incidences of eGFR less than 60 mL/min/1.73 m2, new-onset albuminuria, and end-stage kidney disease.ResultsA total of 269 651 patients were assessed (mean [SD] age, 57.4 [12.5] years; 252 171 [94%] men). Among these, 29 501 patients (10.9%) started uric acid-lowering therapy, and 240 150 patients (89.1%) did not. Baseline characteristics, including serum uric acid level, were similar among treated and untreated patients after propensity score weighting. In the overall cohort, uric acid-lowering therapy was associated with higher risk of both incident eGFR less than 60 mL/min/1.73 m2 (weighted subhazard ratio [SHR], 1.15 [95% CI, 1.10-1.20; P < .001) and incident albuminuria (SHR, 1.05 [95% CI, 1.01-1.09; P < .001) but was not associated with the risk of end-stage kidney disease (SHR, 0.96 [95% CI, 0.62-1.50]; P = .87). In subgroup analyses, the association of uric acid-lowering therapy with worse kidney outcomes was limited to patients with baseline serum uric acid levels of 8 mg/dL or less.Conclusions and relevanceThese findings suggest that in patients with kidney function within reference range, uric acid-lowering therapy was not associated with beneficial kidney outcomes and may be associated with potential harm in patients with less severely elevated serum uric acid levels.

Project description:Background: Hyperuricemia is very common in patients with chronic kidney disease (CKD); the role of hyperuricemia in the occurrence and progression of kidney disease remains an interesting and unresolved issue for nephrologists, and whether urate-lowering therapy (ULT) is warranted in CKD patients is still in controversy. To summarize and compare the clinical outcomes and adverse events (AEs) of three common ULT drugs, we performed a systematic review and network meta-analysis of randomized clinical trials (RCTs). Method: PubMed, MEDLINE, Clinical Trials.gov, EMBASE, and the Cochrane Central Register of Controlled Trials electronic databases were searched. The network meta-analysis was performed using the "gemtc 0.8-7" and its dependent packages in R software. The primary outcome was the change of renal function and uric acid; creatinine, proteinuria, blood pressure, and adverse events were assessed as the secondary outcomes. Results: 16 RCTs involving 1,943 patients were included in the final network analysis. Febuxostat, allopurinol, and benzbromarone were not found to exert superior effects over placebo upon renoprotective effect. With respect to lowering urate, the three drugs showed to be statistically superior to placebo, while febuxostat could better lower urate than allopurinol (MD: -1.547; 95% CrI: -2.473 to -0.626). It is also indicated that febuxostat was superior to placebo at controlling blood pressure, while no differences were observed when allopurinol and benzbromarone were compared to placebo. These results are stable in subgroup analysis. Conclusion: There is insufficient evidence to support the renoprotective effects of the three urate-lowering agents in CKD patients with hyperuricemia; febuxostat shows a tendency to be superior to allopurinol on lowering the decline of eGFR and increment of proteinturia, but the difference does not reach a statistical significance. Regarding its urate-lowering effect, febuxostat appears to be a satisfactory alternative to allopurinol and benzbromarone, and can control blood pressure better.

Project description:IntroductionHyperuricaemia has been implicated in the development of kidney function in populations with chronic kidney disease; however, the benefits of urate-lowering therapy (ULT) remain uncertain in different clinical studies. The different kidney functions of enrolled populations and distinct pharmacokinetic characteristics of ULT might be of the essence for the contrasting results. In this study, we will synthesise all available data from randomised controlled trials (RCTs) and cohort studies, then evaluate the outcomes of ULT in patients stratified by different estimated glomerular filtration rate (eGFR) stratifications. Furthermore, we will attempt to explore a relatively optimal ULT regimen using a Bayesian network meta-analysis in different eGFRs.Methods and analysisWe searched published and unpublished data from MEDLINE, EMBASE, the Cochrane Central Register of Controlled trials and ClinicalTrials.gov website (before March 2022) for RCTs and cohort studies without language restriction. In the pairwise meta-analysis, all regimens of ULT will be pooled as a whole and compared with controls in different eGFRs. The random-effects model will be applied to generate the summary values using the software Stata V.12.0 (StataCorp). Network meta-analysis within a Bayesian framework will be conducted to explore the relative efficacy profiles of different ULTs and to find optimal ULT in different eGFRs. The software of WinBUGS V.1.4.3 and R2WinBUGS package of R V.3.1.1 will be used in the network meta-analysis. Primary outcomes will be the occurrence of major cardiovascular events and kidney failure events. Secondary outcomes will include the rate of change in eGFR per year, all-cause death, changes in serum uric acid level and major adverse events. Two authors will independently review study selection, data extraction and quality assessment.Ethics and disseminationThe meta-analysis does not require ethical certification. The results will be disseminated through publication in a peer-reviewed journal and through presentations at academic conferences.Prospero registration numberCRD42021226163.

Project description:Background: Serum uric acid levels have been shown to be associated with increased risk of diabetes. However, it remains unclear whether uric acid-lowering therapy (ULT) is associated with improved glycemic status. This study aimed to summarize evidence from randomized controlled trials (RCTs) to investigate whether ULT reduces fasting blood glucose (FBG) and glycated hemoglobin A1c (HbA1c) levels. Methods: PubMed, Embase, and the Cochrane Library were searched from inception until April 10, 2019. Moreover, in order to maximize the search for articles on the same topic, the reference lists of included studies, relevant review articles and systematic reviews were reviewed. Parallel RCTs investigating the effect of ULT on FBG or HbA1c levels were considered for inclusion. An English language restriction was applied. Data were screened and extracted independently by two researchers. Meta-analyses were performed using random-effects models to calculate the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Results: Four trials with 314 patients reported the effect of ULT with allopurinol on FBG and 2 trials with 141 patients reported the effect of ULT with allopurinol on HbA1c. Treatment with allopurinol resulted in a significant decrease in FBG (WMD: −0.61 mmol/L, 95% CI: −0.93 to −0.28), but only a trend of reduction in HbA1c (WMD: −0.47%, 95% CI: −1.16 to 0.22). Notably, the subgroup analyses showed that treatment with allopurinol was associated with reduced FBG levels in patients without diabetes (WMD: −0.60 mmol/L, 95% CI: −0.99 to −0.20), but not in patients with diabetes. In addition, the dose of allopurinol treatment ≥200 mg daily resulted in a reduction of FBG levels (WMD: −0.59 mmol/L, 95% CI: −0.95 to −0.23), whereas low-dose allopurinol (<200 mg daily) had no effect on FBG levels. Conclusions: The findings suggest that ULT with allopurinol may be effective at reducing glycemia, but such an improvement does not appear to be observed in patients with diabetes. The findings require confirmation in additional trials with larger sample sizes.

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Effects of uric acid-lowering therapy in patients with chronic kidney disease: A meta-analysis.

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Effects of uric acid-lowering therapy in patients with chronic kidney disease: A meta-analysis.

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