Hyperuricemia, urate-lowering therapy, and kidney outcomes: a systematic review and meta-analysis

Abstract

Background: Contradictory 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. Methods: MEDLINE, 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. Results: Of 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. Conclusion: Hyperuricemia is associated with worsening eGFR, albuminuria, chronic kidney disease, and kidney failure. ULT use for ⩾1 year may improve kidney function. Registration: The protocol was registered at PROSPERO database, CRD42015013859.