Effect of Febuxostat on the Endothelial Dysfunction in Hemodialysis Patients: A Randomized, Placebo-Controlled, Double-Blinded Study

Abstract

Background: Endothelial dysfunction is an important risk factor for cardiovascular diseases to occur in end-stage renal disease patients. Febuxostat, being a novel xanthine oxidase inhibitor, is apparently having a beneficial role in improving the endothelial dysfunction; however, data among hemodialysis patients are still limited. Methods: A prospective, placebo-controlled, block-randomized, double-blinded study was carried out to evaluate the effect of oral febuxostat on the endothelial dysfunction in hemodialysis patients. Fifty-seven eligible hemodialysis patients were randomly assigned to either the drug group (40 mg thrice weekly) or the placebo group. Serum Asymmetric dimethylarginine (ADMA), Serum uric acid (UA), and serum high sensitivity C-reactive protein (hsCRP) were measured at baseline and at the end of a 2-month study. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and the occurrence of pancytopenia were tested as safety parameters at baseline and at the end of study. Results: Serum UA significantly decreased from 7.5 ± 0.8 to 5.1 ± 1.2 mg/dL in the febuxostat group, while it did not change significantly in the placebo group. Treatment with febuxostat resulted in a significant decrease in the serum ADMA level from 1.027 ± 0.116 to 0.944 ± 0.104 µmol/L and the serum hsCRP level from 12.5 ± 1.65 to 12.1 ± 1.70 mg/L. Testing of serum ALT, serum AST, and pancytopenia revealed no significant difference in both groups. Conclusion: Febuxostat appears to improve hyperuricemia and endothelial dysfunction and ameliorate inflammation in hemodialysis patients with no safety concerns.

Effects of uric acid-lowering therapy on the progression of chronic kidney disease: a systematic review and meta-analysis

“…This meta-analysis included reducing urate production with xanthine oxidase inhibitors rather than uricosuric increasing uric acid excretion exactly. Xanthine oxidase inhibitors including allopurinol and febuxostat inhibited oxygen species (ROS) formation and also improved several different measures of endothelial dysfunction in CKD [17, 34 ]. Moreover, xanthine oxidase inhibitors may decrease glomerular hydrostatic pressure and alleviate renal damage through reducing uric acid level.…”

Class effect of xanthine oxidase inhibitors on flow‐mediated dilatation in hypertensive patients: A randomized controlled trial

“…In a rat model, a previous study demonstrated that a therapeutic dose of febuxostat appropriate for hyperuricemia considerably improved endothelial dysfunction . Alshahawey et al randomized 57 hemodialysis patients into a febuxostat treatment group and control group and followed them over two months. They concluded that febuxostat improved endothelial dysfunction, but they used asymmetric dimethylarginine as the index of endothelial dysfunction.…”

Febuxostat administration for the prevention of tumour lysis syndrome: A meta‐analysis

“…Animal studies have proposed that febuxostat is able to ameliorate oxidative stress, as well as to reduce inflammation and enhance insulin sensitivity . It has been also suggested that it presents significant renoprotective properties, since its administration was able to delay chronic kidney disease progression and improve endothelial function in dialysis patients …”

“…12 It has been also suggested that it presents significant renoprotective properties, since its administration was able to delay chronic kidney disease progression 13 and improve endothelial function in dialysis patients. 14 Growing interest exists regarding the potential role of febuxostat in the prevention of TLS. However, although several recent studies have investigated its effectiveness, there is no firm consensus concerning whether it should be considered as an alternative to allopurinol.…”