Renoprotective Effects of Pemafibrate in Patients with CKD: An Open-Label, Randomized, Controlled Trial (PROFIT-CKD Study)

Background: Patients with elevated serum triglyceride (TG) levels are more likely to progress chronic kidney disease (CKD); however, it remains unclear whether lowering serum TG levels confers renoprotective benefits. This study aims to evaluate the renoprotective effect of Pemafibrate, a selective PPARα agonist, in patients with CKD. Methods: In this multicenter, open-label, randomized controlled trial, 145 non-dialysis CKD patients with hypertriglyceridemia (fasting serum TG 150 mg/dL and over) were assigned to either a Pemafibrate treatment group or a conventional therapy group for a 12-month intervention. In the conventional therapy group, neither placebo nor control drugs were used. The primary outcome was the change in the spot urine protein-to-creatinine ratio (UPCR) from baseline, analyzed using a mixed-effects model. Results: After obtaining informed consent, 73 patients were allocated to the Pemafibrate group and 72 to the conventional therapy group. The between-group least squares mean difference in the change in log-transformed UPCR at 12 months was 0.22 (95% CI: -0.05 to 0.49), showing no statistically significant difference (P = 0.11). Among the secondary outcomes, liver and biliary enzymes and lipid metabolism markers significantly improved in the Pemafibrate group, while kidney function and inflammatory markers did not differ significantly between groups. In an exploratory subgroup analysis, among subgroups with diabetic nephropathy, the decline in estimated glomerular filtration rate (eGFR) was significantly attenuated in the Pemafibrate group compared to the conventional group (least squares mean difference: 6.2; P = 0.02). Notably, this effect was similarly observed in the obese (BMI ≥ 25 kg/m2) subgroup of patients with diabetic nephropathy (least squares mean difference: 7.2; P = 0.02), but not in the group without obesity (least squares mean difference: 0.15; P = 0.95). Conclusion: In non-dialysis CKD patients, Pemafibrate treatment did not significantly alter proteinuria compared to conventional therapy; however, it may be beneficial in patients with diabetes nephropathy, especially with obesity.