Exploratory Pilot Study of Exercise-Associated Klotho Modulation in Hemodialysis Patients

Background: Chronic kidney disease (CKD) is characterized by accelerated aging and decline in physical function. Klotho, an anti-aging protein predominantly expressed in the kidney, plays a crucial role in mineral metabolism and longevity. Exercise has been proposed as a non-pharmacological strategy to enhance Klotho expression; however, clinical evidence in hemodialysis patients remains limited. Objective: This study aimed to explore the association between exercise and plasma Klotho levels using a combined case study and cross-sectional design. Methods: This study included: (1) A prospective case study evaluating the effects of high-intensity interval training (HIIT) in a hemodialysis patient. (2) A cross-sectional analysis comparing plasma Klotho levels between hemodialysis patients (n=24) and healthy controls (n=18) and assessing their association with habitual physical activity. Plasma Klotho levels were measured using ELISA. Statistical analyses included the Mann–Whitney U test and Spearman’s correlation coefficient. Results: In the case study, improvements in muscle strength and exercise tolerance were observed following HIIT, allowing the patient to resume daily occupational activities. In the cross-sectional analysis, plasma Klotho levels were significantly lower in hemodialysis patients than in healthy controls (p=0.0001). A moderate positive correlation was observed between exercise habits and plasma Klotho levels in hemodialysis patients (r=0.52, p=0.02), whereas no significant association was found in healthy individuals. Conclusion: These findings suggest that exercise therapy may exert potential anti-aging implications in hemodialysis patients through modulation of Klotho expression. This study provides translational evidence linking clinical rehabilitation and molecular aging pathways.