Long-Term Physical Exercise for Preventing CKD in Older Adults

Background: Chronic kidney disease (CKD) is a growing global public health issue. Physical exercise mitigates several kidney-related pathophysiological pathways, yet its impact on kidney function remains underexplored. We investigated the dose-response effect of physical exercise on kidney function preservation in older adults. Methods: Post-hoc analysis of the Generation 100 Study, a 5-year open-label, randomized, parallel-arm clinical trial conducted from 2012 to 2018 in Trondheim, Norway. All inhabitants aged 70-77 years were invited (n=6,966). Main exclusion criteria were dementia; severe, uncontrolled cardiovascular disease or hypertension; or conditions precluding exercise. The control group (n=385) received information on national physical activity recommendations. Intervention groups underwent supervised moderate-intensity continuous training (70% of peak heart rate) for 50 minutes (n=380) twice weekly for five years or high-intensity interval training (90% of peak heart rate) for 4 minutes x4 (n=391) twice weekly for five years. The primary outcome was cystatin C-based rapid eGFR decline (>5mL/min/1.73m 2 per year). Results: A total of 1,156 participants were randomized with median (interquartile range) age 72 (3) years and eGFR 95 (20) mL/min/1.73 m 2 . Oxygen uptake increased by 1.8, 2.3, and 3.3 mL/kg/min in the control, moderate-intensity, and high-intensity groups. Rapid eGFR decline occurred in 117 (30%), 108 (28%), and 92 (23%) participants, respectively. Compared to controls, relative risk (RR) was 0.93 (0.75-1.16) for moderate-intensity and 0.75 (95% CI 0.59-0.95) for high-intensity, demonstrating a significant dose-response relationship (P for trend 0.02). In observational analyses, participants with decreasing moderate-vigorous activity (> -20 minute/week) had RR 1.30 (95% CI 0.93-1.83) for rapid eGFR decline, while those with increasing activity (> +20 minutes/week) had RR 0.73 (0.53-0.99) compared to stable activity after adjusting for baseline age, sex, VO 2peak and eGFR. Conclusions: High-intensity interval training significantly reduced the risk of rapid eGFR decline in older adults.