Associations of fibroblast growth factor 21 with renal parameter changes during pemafibrate treatment in patients with type 2 diabetes

Abstract Background Experimental studies suggest that fibroblast growth factor 21 (FGF21) is involved in pathways related to peroxisome proliferator-activated receptor alpha (PPARα) activation, whereas elevated circulating FGF21 has also been associated with metabolic stress and kidney dysfunction. We examined the associations of FGF21 with renal parameter changes following the initiation of pemafibrate, a selective PPARα modulator, in patients with type 2 diabetes mellitus (T2DM). Methods In this retrospective study using prospectively collected blood samples, 81 patients with T2DM who initiated pemafibrate and continued treatment for ≥ 2 years were analyzed. Clinical data and serum high-sensitivity C-reactive protein (hsCRP) and FGF21 levels were assessed at baseline and two years. The main outcomes were changes in estimated glomerular filtration rate (eGFR) and log-transformed urinary albumin-to-creatinine ratio (UACR). Multivariable linear regression analyses were performed. Results During the two-year observation period, triglyceride, hsCRP, and UACR levels decreased, whereas FGF21 increased; eGFR remained stable. The change in eGFR was more favorable in patients with baseline eGFR of 30 to < 60 mL/min/1.73 m 2 than in those with eGFR ≥ 60 mL/min/1.73 m 2 . Higher baseline FGF21 and greater increases in FGF21 remained associated with less favorable changes in eGFR and UACR in multivariable analyses. Conclusions Higher baseline FGF21 and greater increases in FGF21 were associated with less favorable renal parameter changes after pemafibrate initiation. Because this observational study lacked a control group, causal effects cannot be inferred. Prospective controlled studies are needed to determine the clinical significance of circulating FGF21.