Effects of Exercise Training on Experimental Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Chronic kidney disease (CKD) promotes progressive renal dysfunction through a complex interplay of oxidative stress, chronic inflammation, apoptosis, and metabolic disturbances. This systematic review and meta-analysis aimed to evaluate the effects of exercise training on systemic adaptations as well as tissue-specific renal and muscular mechanisms in CKD rat models. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, PubMed, Embase, and Web of Science were searched from 2000 to 2026. Of 1287 records, 11 studies were included in the systematic review, of which 8 studies were evaluated in the meta-analysis. Methodological quality was assessed using the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist, with scores ranging from 5 to 7 out of 10. Exercise interventions included resistance training, treadmill running, aerobic exercise, and wheel climbing. Exercise training enhanced endothelial function and improved metabolic homeostasis while attenuating reactive oxygen species (ROS) generation and lipid peroxidation through augmentation of endogenous antioxidant defenses. Restoration of redox balance suppressed nuclear factor kappa B (NF-κB) and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome signaling pathways, resulting in reductions in pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). These effects subsequently mitigated mitochondrial dysfunction, caspase activation, and apoptosis-related signaling, thereby preserving renal cellular viability. These adaptations translated into substantial histopathological protection, characterized by reduced inflammatory cell infiltration, glomerular sclerosis, tubular degeneration, and extracellular matrix deposition. Preservation of renal microarchitecture contributed to improved filtration capacity and overall renal function. Furthermore, exercise promoted mitochondrial biogenesis and anabolic signaling in skeletal muscle via activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/transcription factor A, mitochondrial (TFAM) pathways, enhancing protein synthesis and attenuating CKD-associated muscle wasting, thereby contributing to tissue-level protection and systemic physiological improvement.