Dataset Information

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

ABSTRACT: 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-? (TGF-?) were primary endpoints. Plasma C-reactive protein, high molecular weight-adiponectin, interleukin-6, tumor necrosis factor-?, 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-?/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).

SUBMITTER: Beddhu S

PROVIDER: S-EPMC5332087 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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

Beddhu Srinivasan S Filipowicz Rebecca R Wang Bin B Wei Guo G Chen Xiaorui X Roy Abinash C AC DuVall Scott L SL Farrukh Hanadi H Habib Arsalan N AN Bjordahl Terrence T Simmons Debra L DL Munger Mark M Stoddard Greg G Kohan Donald E DE Greene Tom T Huang Yufeng Y

Canadian journal of kidney health and disease 20161205

<h4>Background</h4>In observational studies, higher uric acid levels are associated with metabolic syndrome, diabetes, and kidney disease.<h4>Objective</h4>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.<h4>Design</h4>This was a double-blinded randomized controlled trial.<h4>Setting</h4>Academic univer ...[more]

PMID: 28270924

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Project description:Background: The levels of circulating tumor necrosis factor receptor (TNFR) 1 and 2 help predict the future decline of estimated glomerular filtration rate (eGFR) chiefly in patients with diabetes. It has been recently reported that the change ratio in TNFR1 by SGLT2 inhibitor treatment is also related with future GFR decline in patients with diabetes. The aims of this study are to investigate the association between baseline TNFR levels and early change in TNFR levels by the non-purine selective xanthine oxidase inhibitor, febuxostat, and future eGFR decline chiefly in chronic kidney disease (CKD) patients without diabetes. Methods: We conducted a post-hoc analysis of the FEATHER study on patients with asymptomatic hyperuricemia and CKD stage 3, who were randomly assigned febuxostat 40 mg/day or matched placebo. This analysis included 426 patients in whom baseline stored samples were available. Serum TNFR levels at baseline were measured using enzyme-linked immunosorbent assay. Those levels were also measured using 12-week stored samples from 197 randomly selected patients. Results: Compared with placebo, short-term febuxostat treatment significantly decreased the median percent change from baseline in serum uric acid (-45.05, 95% CI -48.90 to -41.24 mg/dL), TNFR1 (1.10, 95% CI-2.25 to 4.40), and TNFR2 (1.66, 95% CI -1.72 to 4.93), but not TNFR levels. Over a median follow-up of 105 weeks, 30 patients (7.0%) experienced 30% eGFR decline from baseline. In the Cox multivariate model, high levels of baseline TNFR predicted a 30% eGFR decline, even after adjusting for age, sex, systolic blood pressure, high sensitivity C-reactive protein, uric acid, and presence or absence of febuxostat treatment and diabetes, in addition to baseline albumin to creatinine ratio and eGFR. Conclusion: Early change in circulating TNFR levels failed to predict future eGFR decline; however, regardless of febuxostat treatment, the elevated baseline level of TNFR was a strong predictor of 30% eGFR decline even in chiefly non-diabetic CKD patients with asymptomatic hyperuricemia.

Dataset Information

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

Publications

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

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