Balancing Feasibility and Efficacy

I read with great interest the article by Hallan et al., published in JASN, on the effects of long-term physical exercise, particularly high-intensity interval training (HIIT), in preventing CKD in older adults.1 Although the findings are promising, I would like to raise several points for further discussion and consideration. First, the study highlights the significant benefits of HIIT in reducing the risk of rapid eGFR decline compared with moderate-intensity continuous training and control groups. HIIT, while effective, may pose challenges of adherence and safety in real-world settings, particularly for frail elderly individuals or those with comorbidities such as osteoarthritis or cardiovascular disease. Could a hybrid approach combining HIIT and moderate-intensity continuous training be equally effective while improving feasibility and adherence? In addition, the study reports no cardiovascular events during supervised sessions, but how might these findings translate to unsupervised environments where older adults may lack access to professional guidance? Second, the study's reliance on cystatin C–based eGFR as the primary outcome measure is commendable, given its lower dependence on muscle mass compared with creatinine-based estimates. However, the clinical significance of a >5 ml/min per 1.73 m2 annual decline in eGFR as a primary end point could be debated. Although this threshold aligns with Kidney Disease Improving Global Outcomes guidelines,2 it may not always correlate with meaningful clinical outcomes, such as progression to CKD stages requiring intervention or higher cardiovascular risk. Would incorporating additional end points, such as albuminuria or cardiovascular events, provide a more comprehensive assessment of the benefits of exercise on kidney health? Third, the study's findings raise intriguing questions about the mechanisms underlying the observed benefits of HIIT. The authors suggest that HIIT may reduce inflammation, improve endothelial function, and enhance mitochondrial biogenesis, all of which are relevant to CKD pathophysiology. However, these mechanisms remain speculative in the absence of direct biomarkers or mechanistic studies. Could future research incorporate inflammatory markers, oxidative stress parameters, or renal hemodynamic measurements to elucidate the pathways through which HIIT exerts its protective effects on kidney function? In conclusion, Hallan et al. provided compelling evidence for the role of HIIT in preserving kidney function in older adults. However, translating these findings into clinical practice will require addressing challenges related to feasibility, safety, and scalability.