Authors' Reply: Balancing Feasibility and Efficacy: Reflections on Exercise Interventions for CKD Prevention in Older Adults

Zhang1 raises valid concerns about the feasibility, safety, and scalability of our study “Long-Term Physical Exercise for Preventing CKD in Older Adults: A Randomized Controlled Trial,” published in JASN.2 However, it is important to clarify that high-intensity interval training (HIIT) is not equivalent to all-out sprint training. HIIT is typically performed at 85%–90% of peak heart rate—approximately 20 beats below maximum, and around 60% of each session consists of moderate-intensity activities such as warm-up, active pauses, and cool-down. In addition, participants in the HIIT group were encouraged to complete three unsupervised sessions per week with moderate-intensity continuous training (MICT), making this a hybrid approach. Furthermore, these intensity gradings are relative and age-adapted, meaning a broad range of elderly individuals, including those with varying levels of cardiopulmonary fitness and chronic conditions, can participate in HIIT. Although some elderly individuals may be unable or unwilling to engage in HIIT because of frailty or orthopedic limitations, alternative exercises can often be adapted to enable participation. Safety is a fundamental consideration. HIIT has been extensively tested in diverse patient groups, including 4846 individuals with coronary heart disease, accumulating 175,820 exercise hours and demonstrating a very low risk comparable to MICT.3 In the Generation 100 study, over 50% of the weekly exercise sessions occurred outside the study setting, demonstrating high applicability to unsupervised environments. Participants completed regular safety reports, reviewed by a blinded safety committee, which found no significant differences in adverse events between groups. We are therefore confident that HIIT is both feasible and safe in real-world settings. We concluded that HIIT significantly reduces the risk of rapid eGFR decline in older adults. We agree that relatively few participants—despite experiencing a decline of >5 ml/min per 1.73 m2 per year—would progress to CKD stages requiring intervention since we studied a population with near-normal kidney function. However, even small shifts in risk factor distribution will have a clinically significant effect when applied to large populations.4 Since kidney disease remains asymptomatic until irreversible organ damage occurs, early prevention strategies are crucial in addressing the CKD epidemic. We have also demonstrated the effect of randomizing to MICT versus no exercise in sedentary elderly adults with mean eGFR 54 ml/min per 1.73 m2, i.e., a high-risk population with many patients with CKD.5 We therefore advocate for physical exercise as a vital, yet underutilized, intervention to preserve kidney function. Just as it is well established in cardiovascular disease prevention, exercise should be recognized as a key strategy for CKD, both related to public health and direct patient management.