Exercise-mediated renoprotection across kidney diseases: emerging roles of microRNAs

Exercise exerts renoprotective effects across diverse kidney disease settings, yet the molecular mechanisms underlying these adaptations remain incompletely understood. MicroRNAs (miRNAs), owing to their capacity to regulate multiple targets within interconnected signaling networks, may serve as a regulatory interface between exercise stimuli and renal adaptation. This narrative review synthesizes current understanding of the pathophysiological roles of miRNAs in kidney diseases and emerging evidence linking exercise-associated miRNA remodeling to renoprotection. Particular attention is given to miRNAs involved in metabolic and organelle homeostasis, inflammation and oxidative stress, regulated cell death, and fibrotic remodeling, as well as to exercise-responsive miRNAs detected in renal tissue, extracellular vesicles (EVs), and the circulation. Across experimental models, several candidate pathways, including miR-34a–Klotho, miR-296-5p–SGLT2, and miR-126/Nrf2, show coordinated changes in miRNA expression, related signaling pathways, and renal outcomes. Beyond renal tissue, EV-associated miRNAs suggest a potential route for muscle-kidney communication, while circulating miRNAs may provide biomarkers of systemic responses to exercise. Overall, miRNAs represent an emerging component of the molecular network potentially linking exercise to improved renal outcomes across kidney disease settings, although their specific mechanistic contributions remain to be established.