Background/Purpose: Although allopurinol is the first urate lowering therapy (ULT), its limited dosage in gouty patients with stage 4 or 5 chronic kidney disease (CKD 4/5) prevents to achieve serum urate level (sUA) target (< 6.0 mg/dL). Febuxostat is a nonpurine xanthine oxidase inhibitor with predominant hepatic metabolism and can be used without dosage adjustment in gouty patients with CKD. However, its safety and efficacy in advanced CKD have been reported in only one study and no data are available yet in patients with kidney transplantation (1). 

Methods: In this retrospective multicenter study, clinical records of all gouty patients with estimated glomerular filtration rate (eGFR) ≤ 30 ml/min/1.73 m2 (MDRD formula) at febuxostat initiation and at least after 3 months follow-up period were selected. Items to be collected (demographic data, co-morbidities, renal disease, gout history and former treatments, increasing serum urate drugs, laboratory data and any adverse effects (AEs) were approved by all participant centers. Variables to be analyzed were: sUA level at initiation and last available sUA levels; variation of eGFR; percentage of patients who achieved sUA levels < 6.0 mg/dL and 5.0 mg/dL; flares under ULT and all AEs with specific attention to cardiovascular (CV) events.

Results: Fifty-five gouty patients (mean age 70.7 ± 11.1, 47 men) from 7 French rheumatology departments were included. 26 patients (47.3%) suffered from vascular CKD and 13 patients (23.6%) had received renal transplant. Mean duration of gout was 7 years. 15 patients (27.2%) had tophi and 23 (41.8%) gout arthropathies. Diuretics were used in 47 patients (85.5%). Cardiac dysfunction was present in 9 patients (16.4%). 54 patients had hypertension, 15 (27.3%) diabetes mellitus, 40 (72.3%) dyslipidemia, 19 (34.5%) CV diseases, 20 (36.3%) had past history of vascular events (stroke, myocardial infarction). Mean sUA level and eGFR at febuxostat initiation were 8.8 ± 2.7 mg/dL and 21.3 ± 6.5 ml/min (6-30 ml/min), respectively. Febuxostat initiation dosage was 80 mg daily for 36 patients (65.5%), 80 mg every 2 days for 12 patients (21.8%) and 120 mg daily for 3 patients (5.5%). At last visit (mean follow-up 72 weeks (12-260)) mean sUA level was 4.8 ± 2.2 mg/dL; 39 patients (65.5%) achieved sUA target < 6.0 mg/dL and 34 (61.8%) had sUA ≤ 50 mg/L. Renal function improved (defined by > 10% increase of eGFR from baseline) in 13 patients (23.6%) (mean eGFR change: + 8.4 ml/min), was unchanged in 16 (29.1%) and worsened (defined by > 10 decrease of eGFR from baseline) in 21 (38.2%) (mean sGFR change: -6.3 ml/min). 33 patients experienced flares under febuxostat treatment. AE was observed in one patient who had suffered from limb edema. No CV event was reported during febuxostat exposure.

Conclusion: Febuxostat appears efficient in gouty patients with stage 4/5 CKD or renal transplants. However, safety data is not yet validated with respect to renal function. Further studies with larger samples are warranted for assessing this issue.

1. Shibagaki et al. Safety, efficacy and renal effect of febuxostat in patients with moderate-to-severe kidney dysfunction. Hypertension Res 2014; 37; 919-25

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-febuxostat-in-55-gouty-patients-with-stage-45-chronic-kidney-disease-results-from-a-retrospective-multicenter-study/