UC Davis

Chronic kidney disease (CKD) is a debilitating condition characterized by a gradual decline in kidney function, resulting in decreased glomerular filtration, increased permeability of the filtration barrier, and deficits in secondary renal functions such as vitamin D activation and erythropoietin production. This functional decline leads to secondary complications, including the accumulation of uremic metabolites, chronic acidosis, systemic inflammation, vitamin D deficiency, and low hematocrit. Through these mechanisms, CKD exerts profound systemic effects on extrarenal tissues, particularly within the musculoskeletal and cardiovascular systems. This dissertation explores the specific effects of CKD on tendon, bone, skeletal muscle, and cardiac muscle, and evaluates the efficacy of uphill treadmill exercise as a therapeutic intervention using an adenine-diet-induced CKD rat model. We report the first experimental evidence of tendon dysfunction in CKD, providing a novel platform for mechanistic research. Furthermore, we found that while chronic treadmill exercise successfully maintained skeletal muscle mass, it exhibited limited effects on bone structure and function. Notably, exercise led to weaker tendons in CKD animals, further suggesting that renal disease fundamentally impairs tendon remodeling responses. Finally, CKD completely blunted exercise-induced cardiac hypertrophy in treadmill-trained rats, a maladaptation that appears driven by altered protein turnover. Collectively, this work elucidates the tissue-specific impacts of exercise in the context of CKD, highlighting the underlying mechanisms driving these responses and identifying critical targets for future therapeutic interventions.