Febuxostat, a xanthine oxidase inhibitor, may preserve renal function among certain subgroups of patients with chronic kidney disease (CKD) stage 3 and concomitant asymptomatic hyperuricemia, according to a new study.
The study, by Kenjiro Kimura, MD, of Tokyo Takanawa Hospitak, and collaborators, included 443 patients randomly assigned to receive febuxostat (219 patients) or placebo (222 patients). Both groups had a mean age of 65 years. The mean serum uric acid level was 7.8 mg/dL. The primary study outcome was slope of estimated glomerular filtration rate (mL/min/1.73 m2 per year).
Overall, the eGFR slope did not differ significantly between the febuxostat and placebo groups (0.23 vs ˗0.47), the investigators reported online ahead of print in the American Journal of Kidney Diseases. Subgroup analysis, however, demonstrated that febuxostat was associated with a significant suppression of eGFR decline compared with placebo among patients without proteinuria (1.69 vs ˗0.10) and those whose serum creatinine level was below the median (1.19 vs ˗0.57).
The febuxostat arm had a significantly lower incidence of gouty arthritis than the placebo arm (0.91% vs 5.86%).
The FDA issued a warning about an increased risk of cardiac-related death and all-cause mortality associated with febuxostat compared with allopurinol, but Dr Kimura and collaegues noted that their trial did not find an increased number of cardiovascular events with febuxostat compared with placebo.
In a discussion of study limitations, the authors pointed out that they used estimated rather than measured GFR. “Imprecision and biases inherent in eGFR are greater at higher GFRs, thus restricting the accuracy of classification in the mildly decreased GFR group,” they wrote. In addition, they excluded from their study patents with stage 4 or 5 CKD “because of clinical concerns about the rapid deterioration in kidney function in a short period.” Lastly, “findings from the study might not be generalizable outside of Japan because of the exclusively Japanese study population and the use of a Japan-specific eGFR equation.”
Kimura K, Hosoya T, Uchida S, et al. Febuxostat therapy for patients with stage 3 CKD and asymptomatic hyperuricemia: A randomized trials. Am J Kidney Dis. 2018; published online ahead of print.