#1614 Fenofibrates and chronic kidney disease – Is there anything to worry about?
Authors: Bessa Maria Beatriz , Sousa Sonia , Moreira Carla , Almeida Maria Clara 
Published: May 2024

Abstract

Background and Aims
Chronic Kidney Disease (CKD) patients have increased risk of cardiovascular disease and dyslipidemia is a frequent comorbidity. Many patients are medicated with anti-lipidemic agents to reduce atherosclerotic disease and coronary vascular events. Fenofibrates are lipid-lowering agents used to treat mixed dyslipidemia and hypertriglyceridemia and are widely used by primary care physicians.
Many studies described reversible increase in serum creatinine (SCr) associated with fenofibrates use, but the underlying mechanism is poorly understood. Whether hypercreatinemia is secondary to alterations in creatinine metabolism, tubular handling, or reflects a true impairment in kidney function remains unknown. This phenomenon is also fairly unknown to many primary care providers and, as a result, patients with a SCr rise while on fenofibrates are often referred to nephrology consultation.
In this study, we have analyzed the effect of fenofibrate withdrawal on SCr, eGFR and hemoglobin (Hb) in patients referred to nephrology consultation for CKD or decrease of eGFR. Our aim was to understand the impact of fenofibrates withdrawal on kidney function and to look for factors that might influence the risk of fenofibrate nephrotoxicity.

Methods
We conducted a retrospective observational study, reviewed electronic medical records and collected data of all adult patients discontinued on fenofibrates at first nephrology consultation, between January 2022 and October 2023. Ninety patients were included, of which four were excluded due to simultaneous suspension of antihypertensive drugs.
Patients were subsequently evaluated for clinical reasons from 2 to 6 months after the first appointment, with new laboratory data collected, including Hb, SCr and lipid profile. eGFR was calculated using MDRD 4 formula.
Continuous variables were compared by t-test and categorical variables were compared by chi-square test. A p value of &lt; 0.05 was considered statistically significant. All data was analyzed using Stata software.

Results
A total of eighty-six patients were included in this study, 65% (n=56) were male, mean age of 71.2 ± 11.4 years old; all patients were medicated with fenofibrates due to dyslipidemia and 77% (n=66) were also on statins; 94% (n=81) had hypertension, 60% (n=52) had type 2 diabetes mellitus, and 20% (n=17) had ischemic cardiopathy. Ninety-two percent (n=79) were taking renin-angiotensin system inhibitors (RASi). Nearly half the patients (49% n = 42) had stage 4 CKD and 45% (n = 39) had stage 3 CKD; Main causes of CKD were presumed diabetic kidney disease (34% n = 29) and ischemic nephropathy (15% n = 13), 30% (n = 26) of patients had undetermined etiology.
Upon fibrate discontinuation, mean SCr was 2.1 ± 0.6 mg/dL and mean eGFR was 31.3 ± 10.9 mL/min/1.73 m2. Mean Hb was 12.5 ± 2.0 g/dL.
After fenofibrate discontinuation, eGFR significantly improved in mean 15.2 mL/min/1.73 m2 (31.3 vs 46.5 mL/min/1.73 m2, p &lt; 0.0001) with a mean reduction of SCr of 0.6 mg/dL (2.1 vs 1.5 mg/dL, p &lt; 0.0001). Mean Hb increased 0.4 g/dL (12.4 vs 12.7 g/dL, p = 0.112). Mean total cholesterol was 168.4 ± 56.4 mg/dL and mean triglycerides was 234.8 ± 285.3 mg/dL. Only one patient was restarted on fenofibrate due to severe hypertriglyceridemia. Fenofibrate discontinuation effect on eGFR improvement remained statistically significant when adjusted for diabetes, hypertension, CKD etiology and RASi use.

Conclusion
Our study reports a consistent increase in eGFR and SCr decrease following discontinuation of fenofibrate, as other reports before. A true effect on eGFR could be supported by the Hb rise, though it did not reach statistical significance. The exact mechanism by which fenofibrates increase SCr remains to be clarified.
Cardiovascular disease is the main cause of death amongst CKD population and the potential benefits of fenofibrates should not be disregarded. Our results suggest that patients started on fenofibrates should be carefully selected, specially if CKD is present, and kidney function monitoring should be considered. A drop in eGFR should prompt physicians to weigh on the strict indications for fenofibrates use.