Background: The association between hyperuricemia, gout, and impaired renal function has long been recognized. Recent data provide evidence for the causal relationship between elevated serum urate (sUA) and renal changes, leading to declines in glomerular filtration rates. In healthy adults, glomerular filtration rate wanes with age. Urate-lowering therapy (ULT) with allopurinol has been shown to stabilize or reverse this.
Objective: Here we examine the long-term effects of ULT with febuxostat on estimated glomerular filtration rate (eGFR).
Methods: This is a post hoc analysis of the Febuxostat Open-label Clinical trial of Urate-lowering efficacy and Safety study, during which 116 hyperuricemic gout subjects received daily doses of febuxostat (40, 80, or 120 mg) for up to 5 years. sUA concentrations and eGFR were assessed regularly. Results were stratified by mean change in sUA from baseline. Mathematical modeling was used to predict the effect of sUA reduction on eGFR.
Results: Maintenance or improvement in eGFR was inversely correlated with the quantitative reduction in sUA from baseline. For every 1 mg/dL decrease in sUA, the model projected an expected improvement in eGFR of 1 mL/min from the untreated value.
Conclusion: Individuals with the greatest reductions in sUA may experience reduced rates of renal deterioration or even stabilization of renal function. Further studies examining the impact of long-term ULT on renal function in hyperuricemic gout patients are needed to both confirm our results and verify if improvements in renal function are feasible in such patients.
Mathematical modeling has shown that patients with the greatest magnitude reductions of serum urate were likely to stabilize or improve estimated GFR.
From the *Universal Clinical Research Center, Inc, Hunt Valley; and the Johns Hopkins University School of Medicine, Baltimore, MD; and †Takeda Global Research and Development Center, Inc, Deerfield, IL.
This study was funded by Takeda Global Research and Development Center, Inc.
The FOCUS trial was completely funded by TAP Pharmaceutical Products, Inc, which is now a part of Takeda Global Research & Development Center, Inc, Deerfield, IL. It is registered as NCT00174949 on clinicaltrials.gov.
Assistance in manuscript preparation was provided by Meryl Gersh, PhD, of AlphaBioCom, LLC, in Radnor, PA, and was funded by Takeda Global Research & Development Center, Inc.
Dr Whelton has served as a consultant and speaker for Takeda Global Research & Development Center, Inc. Ms MacDonald, Dr Zhao, Ms Hunt, and Dr Gunawardhana currently are all employees of Takeda Global Research & Development Center, Inc.
Correspondence: Andrew Whelton, MD, 1737 Beaver Brook Lane, Hunt Valley, MD 21030-1603. E-mail: firstname.lastname@example.org