Effects of Febuxostat on Markers of Endothelial Dysfunction and Renal Progression in Patients with Chronic Kidney Disease

Abstract

Abstract Background Hyperuricemia relates to chronic kidney disease (CKD) progression and impaired endothelial function. Febuxostat is potent and effective for decreasing serum uric acid levels. Information for the effect of febuxostat treatment on markers of endothelial dysfunction and renal injury in patients with CKD is limited. Methods A total of 84 CKD stage III-IV patients with asymptomatic hyperuricemia were randomly assigned to either the febuxostat (40 mg/day, N = 42) or the matching control (N = 42) for 8 weeks. Serum asymmetric dimethylarginine (ADMA), estimated glomerular filtration rate (eGFR), urine albumin, high sensitivity C-reactive protein (hs-CRP), ankle brachial index (ABI) and serum uric acid were measured at baseline and at the end of study. Results Febuxostat administration significantly reduced the serum uric acid concentration in patients with CKD when compared with control [-3.40 (95% CI -4.19 to -2.62) vs. -0.35 (95% CI -0.76 to 0.06) mg/dL; P < 0.001, respectively). No significant difference in the changes in serum ADMA, hs-CRP, eGFR and albuminuria was identified between the two groups. Subgroup analysis in patients with decline serum uric acid after febuxostat, the estimated GFR change between the febuxostat and the control group was significant difference at 8 weeks (2.01 (95%CI 0.31 to 3.7) vs. 0.04 (95%CI -1.52 to 1.61) mL/min/1.73 m2; P = 0.030, respectively). Adverse events specific to febuxostat were not observed. Conclusion Febuxostat effectively reduced serum uric acid in the population of CKD without improvement of endothelial dysfunction. It was able to preserve renal function in subgroup CKD patients with lower serum uric acid level after treatment. Trial registration: Thai Clinical Trials, TCTR20210224005: 24/022021 http://www.thaiclinicaltrials.org/show/TCTR20210224005