Comparative effect of allopurinol and febuxostat on long-term renal outcomes in patients with hyperuricemia and chronic
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REVIEW ARTICLE
Comparative effect of allopurinol and febuxostat on long-term renal outcomes in patients with hyperuricemia and chronic kidney disease: a systematic review Anna M. Hu 1
&
Jamie N. Brown 1
Received: 3 February 2020 / Revised: 27 March 2020 / Accepted: 1 April 2020 # International League of Associations for Rheumatology (ILAR) 2020
Abstract Patients with chronic kidney disease (CKD) are more likely to develop hyperuricemia and gout. Allopurinol and febuxostat are the most commonly used urate-lowering therapies with established safety and efficacy in CKD patients. The objective of the systematic review is to assess the long-term renal outcomes of allopurinol compared with febuxostat in patients with hyperuricemia and CKD or kidney transplantation. PubMed MEDLINE, Embase, Web of Science, Scopus, and Cochrane CENTRAL databases were searched from inception to December 2019 using the key terms “allopurinol,” “febuxostat,” “xanthine oxidase inhibitors,” “gout suppressants,” “hyperuricemia,” “gout,” “chronic renal insufficiency,” and “kidney transplantation.” Studies with follow-up duration ≥ 12 months were included. Risk of bias was assessed using the Cochrane Risk Of Bias In Nonrandomized Studies-of Interventions (ROBINS-I) tool. Three retrospective observational studies with follow-up duration ranging from 1 to 5 years were reviewed. Febuxostat patients had a significantly higher estimated glomerular filtration rate, reduced risk for renal disease progression, and reduced serum uric acid levels compared with allopurinol patients. All studies had a serious risk of bias. Febuxostat may be more renoprotective than allopurinol in patients with both hyperuricemia and CKD based on evidence from small long-term retrospective studies with serious risk of bias. More methodologically rigorous studies are needed to determine the clinical applicability of these results. Keywords Allopurinol . Chronic renal insufficiency . eGFR . Febuxostat . Gout . Hyperuricemia . Xanthine oxidase inhibitor
Introduction Patients with chronic kidney disease (CKD) are more likely to develop hyperuricemia (uric acid ≥ 7 mg/dL) and gout compared with those with normal renal function [1]. More than 70% of uric acid is excreted by the kidneys and accumulation occurs with increasing renal impairment [2]. Development of hyperuricemia in CKD may worsen nephropathy through Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10067-020-05079-3) contains supplementary material, which is available to authorized users. * Anna M. Hu [email protected] Jamie N. Brown [email protected] 1
Durham Veterans Affairs Health Care System, Pharmacy Department, Durham, NC 27705, USA
several mechanisms: intrarenal uric acid crystal deposition, systemic uric acid-induced endothelial dysfunction, activation of the renin-angiotensin system, and renal hypertension [3]. Additionally, a growing body of evidence suggests hyperuricemia is an independent risk factor for development of newonset CKD [4–6], progressive CKD [7]
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