The Aging Kidney and Exercise Training Study: protocol for a randomized controlled trial within cohorts (TwiCs) study

Chronic kidney disease (CKD) is a growing global public health concern, particularly in aging population. Despite the strong epidemiological evidence linking physical activity to improved kidney outcomes, interventional findings remain scarce and inconsistent. The primary purpose of the Aging Kidney and Exercise Training Study (AKETS) is to investigate whether a structured exercise program would attenuate the kidney function decline in middle–aged and older adults using a trial within cohorts (TwiCs) design. The AKETS is a 24–month, community–based, randomized controlled trial embedded in the prospective Aging Kidney Study cohort, which started in November 2018. A total of 141 participants aged 40–90 years are enrolled and allocated to one of the following three groups: (1) exercise intervention, (2) stretching intervention (active control), and (3) usual lifestyle (time control). The exercise program comprises individualized multicomponent training, including aerobic, resistance, and balance exercises, performed three times per week over 12 months. The primary outcome is the slope of the estimated glomerular filtration rate (eGFR) based on serum cystatin C. The secondary outcomes include renal hemodynamics, mineral metabolism, cardiovascular function, body composition, muscle strength, and physical performance. At baseline, the exercise, stretching, and usual lifestyle groups were well matched for key demographic and clinical characteristics, such as age, proportion of women, and eGFR. Findings from the AKETS will allow for a robust evaluation of exercise as a primary preventive strategy for CKD and are expected to inform future nonpharmacological interventions targeting kidney health in the aging population. This study is registered at the University Hospital Medical Information Network Clinical Trials Registry as UMIN000055825. Registered on the 13th of October 2024.