title: 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.
  
  
  METHODS
  This was a double-blinded randomized controlled trial.
  
  
  METHODS
  Academic university setting was used.
  
  
  METHODS
  Overweight or obese adults with hyperuricemia and type 2 diabetic nephropathy were included.
  
  
  METHODS
  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 m2at baseline to 51 ± 17 mL/min/1.73 m2at 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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  The study was registered in clinicaltrials.gov (NCT01350388).
authors.affiliation: Department of Medicine, University of Utah School of Medicine, Salt Lake City, USA; Department of Veterans Affairs, Salt Lake City Health Care System, UT, USA.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Beddhu
authors.affiliation: Department of Medicine, University of Utah School of Medicine, Salt Lake City, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Filipowicz
authors.affiliation: Department of Medicine, University of Utah School of Medicine, Salt Lake City, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Medicine, University of Utah School of Medicine, Salt Lake City, USA.
authors.forename: Guo
authors.initials: G
authors.lastname: Wei
authors.affiliation: Department of Medicine, University of Utah School of Medicine, Salt Lake City, USA.
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Medicine, University of Utah School of Medicine, Salt Lake City, USA.
authors.forename: Abinash C
authors.initials: AC
authors.lastname: Roy
authors.affiliation: Department of Medicine, University of Utah School of Medicine, Salt Lake City, USA; Department of Veterans Affairs, Salt Lake City Health Care System, UT, USA.
authors.forename: Scott L
authors.initials: SL
authors.lastname: DuVall
authors.affiliation: Department of Medicine, University of Utah School of Medicine, Salt Lake City, USA.
authors.forename: Hanadi
authors.initials: H
authors.lastname: Farrukh
authors.affiliation: Department of Medicine, University of Utah School of Medicine, Salt Lake City, USA.
authors.forename: Arsalan N
authors.initials: AN
authors.lastname: Habib
authors.affiliation: Department of Medicine, University of Utah School of Medicine, Salt Lake City, USA.
authors.forename: Terrence
authors.initials: T
authors.lastname: Bjordahl
authors.affiliation: Department of Medicine, University of Utah School of Medicine, Salt Lake City, USA; Department of Veterans Affairs, Salt Lake City Health Care System, UT, USA.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Simmons
authors.affiliation: University of Utah School of Pharmacy, The University of Utah, Salt Lake City, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Munger
authors.affiliation: Department of Medicine, University of Utah School of Medicine, Salt Lake City, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Stoddard
authors.affiliation: Department of Medicine, University of Utah School of Medicine, Salt Lake City, USA; Department of Veterans Affairs, Salt Lake City Health Care System, UT, USA.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Kohan
authors.affiliation: Department of Medicine, University of Utah School of Medicine, Salt Lake City, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Greene
authors.affiliation: Department of Medicine, University of Utah School of Medicine, Salt Lake City, USA.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Huang
keywords: chronic kidney disease (CKD); diabetic nephropathy; fibrosis; inflammation; oxidative stress