Fenofibrate-Associated Nephrotoxicity Common in Patients With Gout

Fenofibrate-associated nephrotoxicity occurs frequently in patients with gout, particularly among those with tophi and chronic kidney disease (CKD), according to study results published in Rheumatology.

Researchers sought to explore the incidence and potential risk factors for the development of fenofibrate-related nephrotoxicity in patients with gout.

A retrospective, population-based cohort study was conducted in patients with gout who visited the gout clinic at the Affiliated Hospital of Qingdao University in Qingdao, China, between September 2016 and June 2020. All participants were diagnosed with gout according to the 2015 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) criteria. In the current study, the researchers defined nephrotoxicity as an increase in serum creatinine (SCr) of 0.3 mg/dL or higher within the initial 6 months of fenofibrate therapy. The change trend in SCr and uric acid levels during treatment were evaluated using a generalized additive mixed model (GAMM).

The primary study outcome was the trends and predictors for fenofibrate-associated nephrotoxicity. Secondary outcomes included medications and comorbidities that predisposed individuals to nephrotoxicity; and the time course for nephrotoxicity, evaluated by changes in SCr during the treatment period, as well as the temporal relationship between initiation of treatment and increase in SCr.

A total of 983 participants from the gout clinic were included in the current analysis. Median duration of treatment with a fixed dose of fenofibrate 200 mg/day was 51 days (range, 28-98 days). Two groups of patients were identified, namely, the nephrotoxicity group (patients in whom a peak creatinine value during the follow-up period minus the baseline creatinine value was ≥0.3 mg/dL), and the non-nephrotoxicity group (those in whom these values were not observed).

Overall, 10.17% of participants (n=100) experienced an elevation in SCr levels of 0.3 mg/dL or higher following fenofibrate administration. Median change in SCr levels in the entire cohort was 0.11 mg/dL (range, 0.03-0.20 mg/dL) vs 0.36 mg/dL (range, 0.33-0.45 mg/dL) in the fenofibrate-associated nephrotoxicity group.

According to multivariable regression analysis, CKD (odds ratio [OR], 2.39; 95% CI, 1.48-3.86) and presence of tophi (OR, 2.29; 95% CI, 1.39-3.78) were shown to be risk factors for fenofibrate-related nephrotoxicity. After the withdrawal of fenofibrate, elevated SCr levels were reversible in 65.6% of participants after an average of 49 days. In addition, the difference in SCr increase (according to interaction analysis in GAMM) was 0.0019 mg/dL per day (95% CI, 0.0016-0.0022 mg/dL per day; P <.001) between the 2 groups.

Major limitations of the current study included its retrospective, observational design, and the fact that any long-term effects were not evaluated.

Researchers concluded that the current study “provided significant evidence to the notion that prescribing fenofibrate should be done cautiously in clinical practice” in patients with gout, particularly those with tophi and CKD. They added that results from this evidence-based study may contribute to the development of guidelines.

Reference

Li X, Sun W, Lu J, et al. Effects of fenofibrate therapy on renal function in primary gout patients. Rheumatology. Published online March 11, 2021. doi:10.1093/rheumatology/keab231