Selective peroxisome proliferator-activated receptor-α modulator improves hypertriglyceridemia and muscle quality in patients with chronic kidney disease: A retrospective observational study

Abstract

Background & aims: Patients with chronic kidney disease (CKD) often have additional health problems, including sarcopenia and sarcopenic obesity. These conditions involve ectopic fat accumulation within muscles. This ectopic fat deposition reduces muscle quality, leading to weaker muscle strength and poorer physical performance. Persistent hypertriglyceridemia contributes to ectopic fat accumulation. Metabolic abnormalities, including dyslipidemia, are major factors in CKD development. Triglycerides (TG) and muscle quality are thus important factors in CKD management. Recently developed selective peroxisome proliferator-activated receptor α modulator (SPPARMα) hold promises for improving hypertriglyceridemia. However, their effectiveness and impact on muscle quality in CKD patients remain unclear. This study aimed to evaluate the effect of SPPARMα on muscle quality and its efficacy in CKD patients.

Methods: This retrospective observational study involved CKD patients with dyslipidemia. We included patients who initiated medications for hypertriglyceridemia. We compared changes in lipid profiles, renal function, and muscle quality, assessed by phase angle, over six months between two groups: those receiving this type of medication and those receiving conventional treatment.

Results: Among 245 patients diagnosed with CKD and hypertriglyceridemia, 52 started medications for hypertriglyceridemia. Of these, 26 received SPPARMα, and 26 received conventional lipid-lowering medications (statins, ezetimibe, eicosapentaenoic acid, and fibrates). SPPARMα significantly reduced TG (from 296.8 ± 106.1 to 153.0 ± 86.1, p < 0.001) without affecting glomerular filtration rate or urinary protein levels. Conventional treatment also improved TG (from 261.6 ± 89.5 to 173.6 ± 81.3, p < 0.001). Only patients treated with SPPARMα showed significant improvement in muscle quality. Their phase angle increased from 5.41 ± 0.6 to 5.55 ± 0.6 after six months of treatment (p < 0.05).

Conclusions: Our study demonstrates that the newly developed SPPARMα significantly lowers TG levels in CKD patients without harming their kidneys. Additionally, only patients treated with SPPARMα showed improvement in muscle quality. These findings suggest that SPPARMα may be a valuable treatment option for CKD patients with dyslipidemia, particularly those with low muscle quality.

Keywords: CKD; Muscle quality; Pemafibrate; Phase angle; SPPARMα; Sarcopenic obesity.