Department of Endocrinology and Metabolism, Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University.
Institute of Metabolic Diseases, Qingdao University, Qingdao, China.
Rheumatology (Oxford). 2021 Nov 3;60(11):5020-5027. doi: 10.1093/rheumatology/keab231.
To investigate the incidence and potential risk factors for development of fenofibrate-associated nephrotoxicity in gout patients.
A total of 983 gout patients on fenofibrate treatment who visited the dedicated Gout Clinic at the Affiliated Hospital of Qingdao University between September 2016 and June 2020 were retrospectively enrolled from the electronic records system. Fenofibrate-associated nephrotoxicity was defined as an increase in serum creatinine (SCr) ≥0.3 mg/dl within 6 months of fenofibrate initiation. The change trend of SCr and uric acid levels during the treatment period were assessed by a generalised additive mixed model (GAMM). Multivariate analysis was performed for risk factors affecting elevated SCr.
A total of 100 (10.2%) patients experienced an increase in SCr ≥0.3 mg/dl within 6 months after fenofibrate initiation. The median change of SCr in the whole cohort was 0.11 mg/dl [interquartile range (IQR) 0.03-0.20], whereas it was 0.36 (0.33-0.45) in the fenofibrate-associated nephrotoxicity group. In a multivariable regression model, chronic kidney disease (CKD) [odds ratio (OR) 2.39 (95% CI 1.48, 3.86)] and tophus [OR 2.29 (95% CI 1.39, 3.78)] were identified to be risk predictors, independent of measured covariates, of fenofibrate-associated nephrotoxicity. During the treatment period, although SCr temporarily increased, serum urate and triglyceride concentrations decreased using the interaction analysis of GAMM. Of those with fenofibrate withdrawal records, the SCr increase in 65% of patients was reversed after an average of 49 days off the drug.
This observational study implied that fenofibrate-associated nephrotoxicity occurs frequently in gout patients, especially in patients with tophi or CKD. The potential renal risks of fenofibrate usage in gout needs additional research.
研究在痛风患者中,非诺贝特相关肾毒性的发生情况及潜在危险因素。
回顾性纳入 2016 年 9 月至 2020 年 6 月期间在青岛大学附属医院痛风专科就诊并接受非诺贝特治疗的 983 例痛风患者,从电子病历系统中提取数据。非诺贝特相关肾毒性定义为起始非诺贝特治疗后 6 个月内血清肌酐(SCr)升高≥0.3mg/dl。采用广义相加混合模型(GAMM)评估治疗期间 SCr 和尿酸水平的变化趋势。采用多变量分析评估影响 SCr 升高的危险因素。
共有 100 例(10.2%)患者在起始非诺贝特治疗后 6 个月内出现 SCr 升高≥0.3mg/dl。全队列 SCr 的中位数变化为 0.11mg/dl[四分位间距(IQR)0.03-0.20],而非诺贝特相关肾毒性组则为 0.36(0.33-0.45)。多变量回归模型显示,慢性肾脏病(CKD)[比值比(OR)2.39(95%置信区间[CI]:1.48,3.86)]和痛风石[OR 2.29(95% CI:1.39,3.78)]是除了测量协变量之外,非诺贝特相关肾毒性的独立危险因素。在治疗期间,虽然 SCr 暂时升高,但通过 GAMM 的交互分析发现,血清尿酸和甘油三酯浓度降低。在有非诺贝特停药记录的患者中,65%的患者在停药平均 49 天后 SCr 升高得到逆转。
本观察性研究表明,非诺贝特相关肾毒性在痛风患者中较为常见,尤其是在有痛风石或 CKD 的患者中。在痛风患者中使用非诺贝特可能存在潜在的肾毒性风险,需要进一步研究。