High-Intensity Interval and Aerobic Training Alleviate Cardiac Pathology, Apoptosis, and Atrial Fibrillation in Rats With Chronic Kidney Disease: The Roles of Fgf23 and Klotho Publisher Pubmed



Rokhsati S ; Shahsavari N ; Rabbani S ; Suzuki K ; Khoramipour K
Source: Biomolecules Published:2026

Abstract

Chronic kidney disease (CKD) leads to metabolic and cardiovascular complications, and the dysregulation of key biomolecules, namely fibroblast growth factor 23 (FGF23) and Klotho, plays a central role. This study investigated the effects of high-intensity interval training (HIIT) and moderate aerobic training (AT) on FGF23, Klotho, mineral metabolism, apoptosis markers (BAX, Bcl2), and atrial fibrillation (AF) in a rat CKD model. The study used 35 Wistar rats randomly assigned to control (CTL), sham (SH), CKD, CKD + HIIT, and CKD + AT groups. CKD was induced by 5/6 nephrectomy surgery. Exercise interventions consisted of eight weeks of HIIT (80–100% of maximum speed, 24–54 min/week) or AT (45–55% of maximum speed, 40–60 min/week), conducted three times weekly on a treadmill. We measured heart weight, blood levels of FGF23, Klotho, and mineral metabolism markers, as well as the heart expression of apoptosis proteins (i.e., BAX, Bcl2) and atrial fibrillation (AF). Both exercise types reduced the heart weight and heart/body weight ratio; attenuated CKD-induced elevations in FGF23 and reductions in Klotho; improved blood levels of phosphate, PTH, and vitamin D; and modulated apoptotic markers by decreasing BAX and increasing Bcl2 levels. Exercise improved cardiac function and reduced the AF duration. These findings emphasize that exercise could be a helpful non-pharmacological intervention to ameliorate CKD-induced cardiovascular and metabolic disturbances through the modulation of the FGF23 and Klotho pathways. © 2026 by the authors.