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Effectiveness of Drug Treatments for Lowering Uric Acid on Renal Function in Patients With Chronic Kidney Disease and Hyperuricemia: A Network Meta-Analysis of Randomized Controlled Trials.

ABSTRACT: 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.

SUBMITTER: Liu X

PROVIDER: S-EPMC8369347 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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:BackgroundContradictory evidence exists for association of hyperuricemia and kidney function. To investigate the association of hyperuricemia and kidney function decline (hyperuricemia question) and effect of urate-lowering therapies (ULTs) on kidney function (ULT question), we performed a systematic review and meta-analysis.MethodsMEDLINE, Embase, Cochrane Central Register of Controlled Trials, and CINAHL were searched from inception to July 2020. We selected observational studies for the hyperuricemia question and controlled trials for the ULT question. Two investigators independently assessed study eligibility and abstracted the data. Risk of bias was assessed using the Newcastle-Ottawa Scale and Cochrane risk of bias tool. Meta-analysis was done using the inverse variance method and random effect model. We estimated odds ratio (OR), hazard ratio (HR), risk ratio (RR), and the mean difference (MD). Evidence certainty was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.ResultsOf 12,037 studies screened, 131 studies with 3,414,226 patients were included. Hyperuricemia was associated with a significant risk of rapid estimated glomerula filtration rate (eGFR) decline ⩾3 ml/min per 1.73 m2 per year (OR 1.38, 95% CI 1.20-1.59; low certainty), albuminuria (OR/HR 1.94, 95% CI 1.34-2.79; very low certainty), chronic kidney disease (OR/HR 2.13, 95% CI 1.74-2.61; very low certainty), and kidney failure (HR 1.53, 95% CI 1.18-1.99; very low certainty). Compared with control, ULT use for ⩾1 year was associated with significantly more improved eGFR (MD 1.81 ml/min per 1.73 m2, 95% CI 0.26-3.35; very low certainty), serum creatinine (MD -0.33 mg/dl, 95% CI -0.47 to -0.19; low certainty), and proteinuria (MD -5.44 mg/day, 95% CI -8.49 to -2.39; low certainty), but no difference in kidney failure.ConclusionHyperuricemia is associated with worsening eGFR, albuminuria, chronic kidney disease, and kidney failure. ULT use for ⩾1 year may improve kidney function.RegistrationThe protocol was registered at PROSPERO database, CRD42015013859.

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Effectiveness of Drug Treatments for Lowering Uric Acid on Renal Function in Patients With Chronic Kidney Disease and Hyperuricemia: A Network Meta-Analysis of Randomized Controlled Trials.

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