A Randomized Controlled Trial of the Effects of Febuxostat Therapy on Adipokines and Markers of Kidney Fibrosis in Asymptomatic Hyperuricemic Patients With Diabetic Nephropathy

• Published in: Canadian journal of kidney health and disease Vol. 3; p. 2054358116675343
• Main Authors: Beddhu, Srinivasan, Filipowicz, Rebecca, Wang, Bin, Wei, Guo, Chen, Xiaorui, Roy, Abinash C., DuVall, Scott L., Farrukh, Hanadi, Habib, Arsalan N., Bjordahl, Terrence, Simmons, Debra L., Munger, Mark, Stoddard, Greg, Kohan, Donald E., Greene, Tom, Huang, Yufeng
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 2016; Sage Publications Ltd; SAGE Publishing
• Subjects: Clinical trials; Diabetes; Diabetic nephropathy; Kidney diseases; Original; Oxidative stress; Plasma; Uric acid; fibrosis; chronic kidney disease (CKD); inflammation; diabetic nephropathy; oxidative stress
• ISSN: 2054-3581; 2054-3581
• DOI: 10.1177/2054358116675343

Background: In observational studies, higher uric acid levels are associated with metabolic syndrome, diabetes, and kidney disease. Objective: The objective of this study is to examine whether reduction of plasma uric acid with febuxostat, a xanthine oxido reductase inhibitor, impacts adipose tissue oxidative stress, adipokines, and markers of systemic inflammation or kidney fibrosis. Design: This was a double-blinded randomized controlled trial. Setting: Academic university setting was used. Patients: Overweight or obese adults with hyperuricemia and type 2 diabetic nephropathy were included. Measurements: Adipose tissue thiobarbituric acid reducing substances (TBARS) and adiponectin concentrations and urinary transforming growth factor–β (TGF-β) were primary endpoints. Plasma C-reactive protein, high molecular weight–adiponectin, interleukin–6, tumor necrosis factor–α, and TBARS and albuminuria were among predefined secondary endpoints. Methods: Participants were randomly assigned to febuxostat (n = 40) or matching placebo (n = 40) and followed for 24 weeks. Results: Baseline plasma uric acid levels were 426 ± 83 µmol/L; 95% completed the study. Estimated glomerular filtration rate (eGFR) declined from 54 ± 17 mL/min/1.73 m2 at baseline to 51 ± 17 mL/min/1.73 m2 at 24 weeks (P = .05). In separate mixed-effects models, compared with placebo, febuxostat reduced uric acid by 50% (P < .001) but had no significant effects on subcutaneous adipose tissue TBARS (−7.4%, 95% confidence interval [CI], 57.4%-101.4%) or adiponectin (6.7%, 95% CI, 26.0%-53.8%) levels or urinary TGF-β/creatinine ratio (18.0%, 95% CI, 10.0%-54.8%) or secondary endpoints. Limitations: Relatively modest sample size and short duration of follow-up. Conclusions: In this population with progressive diabetic nephropathy, febuxostat effectively reduced plasma uric acid. However, no detectable effects were observed for the prespecified primary or secondary endpoints. Trial Registration: The study was registered in clinicaltrials.gov (NCT01350388).