A prospective cohort of gouty arthritis patients presenting with hyperuricemia and chronic kidney disease stage 3 and 4 for the safety, efficacy and renal effect of febuxostat at Changhai Hospital, Shanghai, China

Abstract

Background: Hyperuricemia (HU) is a risk factor for the onset of Chronic Kidney Disease (CKD) and accumulating evidence significantly associates it with disease progression. A major challenge in treating hyperuricemia with traditional Urate-Lowering Drugs (ULDs) are the adverse effects associated with the accumulation of these drugs or their metabolites in CKD patients. Due to these unwanted effects, doses of ULDs are down-regulated to levels commensurate with the kidneys’ ability to excrete their metabolites. This leads to suboptimal efficacy. Febuxostat, a selective Xanthine Oxidase (XO) inhibitor has demonstrated high efficacy in reducing Serum Uric Acid (SUA) levels and is well tolerated in mild kidney disease. However, its efficacy, safety and renal effects have not been studied in patients with advanced kidney disease, hyperuricemia and gout.

Objective: To evaluate the safety, efficacy and renal effects of febuxostat in patients with HU, gout and CKD stage 3 and 4.

Design: This was a 16-week prospective study, single-center, open-label, self-controlled trial.

Methods: Thirty five patients included received febuxostat 40mg/day. Changes in kidney function tests; SUA levels; liver function tests and full blood count were evaluated. Gout was diagnosed based on 2015 ACR/EULAR criteria, and GFR was estimated using the MDRD formula.

Results: Febuxostat decreased SUA levels to a target <360micromol/L for uncomplicated gout in 5 (36%), n=14, and SUA decreased to a target <300micromol/L for complicated gout in 5 (24%), n=21. Changes in eGFR and SUA were statistically significant, with p=0.001 for both at 95% confidence interval. Mean absolute eGFR from baseline to week 16 represented 9.04 ml/min (19.05%), and was attributed to febuxostat (R2 = 0.9556, 96%). Changes in LFTs and full blood count were insignificant. No drug-related AE were reported.

Conclusion: Febuxostat, as a ULD was safe and effective in controlling SUA levels in patients with gout, hyperuricemia and CKD stage 3 and 4. The drug also exerted renoprotective effects in this patient group. The reduction in SUA by febuxostat was associated with improvement in eGFR and overall kidney function, although a causal relationship wasn’t evaluated in this study.