Dataset Information

Effect of Urate-Lowering Therapy on Cardiovascular and Kidney Outcomes: A Systematic Review and Meta-Analysis.

ABSTRACT:

Background and objectives

Several clinical practice guidelines noted the potential benefits of urate-lowering therapy on cardiovascular disease and CKD progression; however, the effect of this regimen remains uncertain. In this systematic review, we aimed to evaluate the efficacy of urate-lowering therapy on major adverse cardiovascular events, all-cause mortality, kidney failure events, BP, and GFR.

Design, setting, participants, & measurements

We systematically searched MEDLINE, Embase, and the Cochrane databases for trials published through July 2020. We included prospective, randomized, controlled trials assessing the effects of urate-lowering therapy for at least 6 months on cardiovascular or kidney outcomes. Relevant information was extracted into a spreadsheet by two authors independently. Treatment effects were summarized using random effects meta-analysis.

Results

We identified 28 trials including a total of 6458 participants with 506 major adverse cardiovascular events and 266 kidney failure events. Overall urate-lowering therapy did not show benefits on major adverse cardiovascular events (risk ratio, 0.93; 95% confidence interval, 0.74 to 1.18) and all-cause mortality (risk ratio, 1.04; 95% confidence interval, 0.78 to 1.39) or kidney failure (risk ratio, 0.97; 95% confidence interval, 0.61 to 1.54). Nevertheless, urate-lowering therapy attenuated the decline in the slope of GFR (weighted mean difference, 1.18 ml/min per 1.73 m² per year; 95% confidence interval, 0.44 to 1.91) and lowered the mean BP (systolic BP: weighted mean difference, -3.45 mm Hg; 95% confidence interval, -6.10 to -0.80; diastolic BP: weighted mean difference, -2.02 mm Hg; 95% confidence interval, -3.25 to -0.78). There was no significant difference (risk ratio, 1.01; 95% confidence interval, 0.94 to 1.08) in the risk of adverse events between the participants receiving urate-lowering therapy and the control group.

Conclusions

Urate-lowering therapy did not produce benefits on the clinical outcomes, including major adverse cardiovascular events, all-cause mortality, and kidney failure. Thus, there is insufficient evidence to support urate lowering in patients to improve kidney and cardiovascular outcomes.

SUBMITTER: Chen Q

PROVIDER: S-EPMC7646244 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

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.

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