Efficacy of Xanthine Oxidase Inhibitors in Lowering Serum Uric Acid in Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Abstract

Objective: Current guidelines for gout recommend a treat-to-target approach with serum uric acid (SUA). However, there is little evidence for the dose-dependent effects of urate-lowering therapy (ULT). Herein, we analyzed the reported SUA-lowering effect and SUA target achievement differences for various doses of xanthine oxidase inhibitors. Methods: Approved ULT drugs were selected from the FDA Drug Database. We included prospective randomized controlled trials of ULT drugs from ClinicalTrials.gov, articles published in the journal “Drugs”, and Embase, a literature database. A meta-analysis was performed to determine the ability of different ULT drugs and doses to lower and maintain a target SUA <6 mg/dL. Results: We identified 35 trials including 8172 patients with a baseline SUA of 8.92 mg/dL. The allopurinol, febuxostat, and topiroxostat showed dose-proportional SUA-lowering responses. Compared with allopurinol 300 mg daily, febuxostat 80 mg daily and 120 mg daily more effectively maintained SUA <6 mg/dL. Conclusion: Allopurinol, febuxostat, and topiroxostat showed dose-proportional ability to lower and achieve a target SUA <6 mg/dL. Significance and Innovations. We showed dose-dependent SUA lowering effects of allopurinol, febuxostat, and topiroxostat. Febuxostat is effective at ULT compared to allopurinol and could be potentially offered as an alternative agent when patients (1) have CKD, (2) have the human leukocyte antigen HLA-B*5801 allele, and (3) become refractory to allopurinol. Gradual allopurinol dose increase with a lower starting dose is needed in CKD.

Navigating the choice between topiroxostat and febuxostat for hyperuricemia management: A prospective comparative study

“…Lee yojin and etal evaluated that an equivalent outcome would be achieved by febuxostat 83.33 mg or topiroxostat 150 mg [3] . Kazuomi Kario in his study on Comparative effects of topiroxostat and febuxostat on arterial properties in hypertensive patients with hyperuricemia gave febuxostat and topiroxostat at dosages of 10-60mg/dl and 40-160mg/dl respectively [4] .…”

Association between oxidative balance score and serum uric acid and hyperuricemia: a population-based study from the NHANES (2011–2018)

“…However, intracellular uric acid has been linked to elevated inflammation and heightened oxidative stress ( 4 ). Extensive research has identified high serum uric acid levels as an independent risk factor for various chronic kidney and joint disorders ( 5 ), including gout ( 6 ), chronic arthritis ( 7 ), joint deformity, and uric acid kidney stones ( 8 ), as well as chronic metabolic diseases such as hypertension ( 9 ), diabetes ( 10 ), and metabolic syndrome, along with cardiovascular disease ( 11 ).…”

Comparison Between Renoprotective Effects of Febuxostat and Allopurinol in Chronic Kidney Disease Patients With Hyperuricemia

“…In lieu of these drugs, xanthine oxidase inhibitors (XOIs) act by inhibiting the xanthine oxidase production which ultimately decreases the uric acid production. Uric acid-lowering drugs reduce oxidative stress and lower the inflammation caused by an accumulation of urate crystals [2]. Thus, curbing hyperuricemia with XOIs may assist in regression or even arrest the progression of CKD [3].…”

“…The most commonly used XOI is allopurinol, which is an analog of hypoxanthine and xanthine; it competes with these molecules in binding xanthine oxidase and inhibits the formation of uric acid. Another is febuxostat, which non-selectively inhibits oxidized and reduced forms of xanthine oxidase [2]. Hence, we conducted this study to compare the renoprotective effects of febuxostat and allopurinol in CKD patients with hyperuricemia.…”