Hyperuricemia, Urate-Lowering Therapy, and Renal Outcomes: A Systematic Review and Meta-Analysis
41 Pages Posted: 8 Nov 2018More...
Background: Evidence describing association between hyperuricemia and declining renal function is contradictory. Our objective was to investigate the effect of 1) hyperuricemia and 2) urate- lowering therapies (ULT), on renal function.
Methods: Medline, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL were searched from inception to January 2016. Observational studies assessing the relationship between serum urate and renal function, and trials evaluating effect of ULTs on renal function were included. 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 as model. Effect estimate measures were odds ratio (OR), hazards ratio (HR), risk ratio (RR) or mean difference (MD). Evidence strength was evaluated using GRADE. The protocol was registered at PROSPERO database, CRD42015013859.
Findings: 7,185 titles/abstracts were retrieved, of which 95 studies with 1,488109 patients were included. Compared to normouricemia, hyperuricemia was associated with a significantly higher risk of developing rapid eGFR decline (≥3mL/min/1·73 m2) (OR, 1·48, 95% CI 1·19 to 1·83, p=0·0004; low certainty), albuminuria (OR/HR, 3·01, 95% CI 2·02 to 4·49, p<0·00001; low certainty), chronic kidney disease (OR/HR, 2·26, 95% CI 1·79 to 2·85, p<0·00001; low certainty), and end-stage renal disease (HR 1·68, 95% CI 1·05 to 2·69, p=0·03; low certainty). Compared to control, ULT use for ≥1 year was associated with significantly more improvement eGFR (MD, 2·60 mL/min/1·73m2, 95% CI, 1·44 to 3·76, p<0·0001; moderate certainty), serum creatinine (MD, -0·45 mg/dl, 95% CI, -0·62 to -0·27, p<0·00001; low certainty), proteinuria/albuminuria (MD, -5·61 mg/day, 95% CI, -8·67 to - 2·55, p=0·0003; low certainty), and a lower risk of renal failure events (RR, 0·43, 95% CI, 0·30 to 0·63, p<0·00001; moderate certainty). ULT use for <1 year was not associated with improvement of renal function.
Interpretation: Hyperuricemia is associated with renal dysfunction. ULT use for ≥1 year significantly improves renal function.
Funding Statement: "None"
Declaration of Interests: GS, AD, and NN have no conflicts of interest. JAS has received research grants from Takeda and Savient pharmaceuticals and consultant fees from Savient, Takeda, Regeneron, Merz, Iroko, Bioiberica, Crealta/Horizon and Allergan pharmaceuticals, WebMD, UBM LLC and the American College of Rheumatology. JAS serves as the principal investigator for an investigator-initiated study funded by Horizon pharmaceuticals through a grant to DINORA, Inc., a 501 (c)(3) entity. JAS is a member of the executive of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from 36 companies; a member of the American College of Rheumatology's (ACR) Annual Meeting Planning Committee (AMPC); Chair of the ACR Meet-the-Professor, Workshop and Study Group Subcommittee; and a member of the Veterans Affairs Rheumatology Field Advisory Committee. JAS is the editor and the Director of the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis.
Ethics Approval Statement: We performed this systematic review and meta-analysis according to the guidelines specified in the Cochrane Handbook for Intervention Reviews and the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. We registered the study protocol in the PROSPERO database, CRD42015013859
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