Background In chronic kidney disease (CKD) patients, hyperuricemia is a common finding and might be one of modifiable risk factors for renal progression. However, dosing adjustments and increased risk of serious side effects of uric acid lowering agents in patients with reduced renal function lead to undercorrection of hyperuricemia, especially in patients with advanced CKD. Febuxostat is highly effective and well-tolerated to treat hyperuricemia in CKD patients. Although several evidences demonstrated the usefulness of febuxostat in hyperuricemic CKD patients, clinical studies aimed at the CKD patients with inappropriately controlled hyperuricemia by allopurinol have been relatively lacking.
Objectives The study objective is to evaluate the safety and efficacy of febuxostat in patients, who had CKD with severe renal impairment and did not meet with the target uric acid levels using allopurinol.
Methods Data were collected from 168 patients who had CKD with more than stage 3b and changed from allopurinol to febuxostat due to uncontrolled hyperuricemia between 2005 and 2014 at Yonsei University Medical Center. Uric acid and creatinine were analyzed at baseline and during the first 6 and 12 months after conversion of febuxostat. Estimated glomerular filtration rate was calculated using the formula of MDRD equation. The patients were defined as a well-controlled state when the uric acid values of the study subjects reached within 6.0 mg/dL.
Results The mean age was 60.7±14.6 years, and 129 patients (76.8%) were male. The number of patients was 25 (14.9%) in CKD stage 3b, 75 (44.6%) in stage 4, 8 (4.8%) in stage 5, 38 (22.8%) in patients treated with maintenance dialysis, 22 (13.1%) in patients underwent kidney transplantation. The mean estimated GFR (eGFR) and uric acid levels at baseline was 23.1±17.3 ml/min/1.73m2 and 8.3±2.4 mg/dL, respectively. Most of the patients was treated with 40 or 80mg of febuxostat during the study period. The mean uric acid levels at 6- and 12-month after febuxostat treatment were significantly reduced compared to uric acid levels at baseline (5.2±2.1 mg/dL at 6-month and 4.9±2.2 mg/dL at 12-month, p<0.001, respectively). More than 70% of study subjects reached to the target of uric acid levels less than 6mg/dL at 6- and 12-months after treatment of febuxostat [122 (72.6%) patients at 6-month and 133 (79.2%) patients]. The creatinine levels at baseline and 6-month were comparable (3.42±2.03 vs. 3.38±2.16 mg/dL at baseline and 6-month, p=0.61), meanwhile, the creatinine levels were significantly increased after 12-month compared to those at baseline (3.69±2.46 mg/dL, p<0.01). Abnormality of liver function test was observed in only one patient during the follow up period. None of the patients did not discontinue drug due to adverse events.
Conclusions Present study demonstrated that substantial hyperuricemic CKD patients treated with febuxostat were achieved the target of uric acid levels without adverse events. Febuxostat is an effective and safe uric acid lowering drug in allopurinol-intolerant patients with advanced CKD.
Disclosure of Interest None declared
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