Cardiorespiratory Fitness and Age-Related Decline in Kidney Function among Individuals with Preserved Kidney Health: The Aging Kidney Study

PURPOSE: Cardiorespiratory fitness (CRF) is a modifiable factor associated with the progression of chronic kidney disease (CKD). However, whether higher CRF levels can help prevent age-related kidney function decline in the early stages before the onset of CKD remains unclear. This study aimed to investigate the effect of CRF on subsequent changes in kidney function in individuals with preserved kidney function under a prespecified causal framework. METHODS: This prospective cohort study assessed CRF by measuring oxygen uptake at the ventilatory threshold using gas exchange analysis during a submaximal exercise test. Kidney function was evaluated annually over 5 years (up to 6 time points per participant) using two estimates of glomerular filtration rate (GFR): serum cystatin C (eGFRcys) and serum creatinine (eGFRcr). The slopes were calculated separately for each estimated eGFR using linear mixed-effects models. Multiple linear regression analyses were conducted to examine the association between CRF and eGFR slope. RESULTS: A total of 198 participants (median age 61.4 years; 74% females) were included in the analyses. CRF was significantly correlated with the slopes of eGFRcys (r = 0.24). After adjusting for confounders, higher levels of CRF were significantly associated with a slower decline in the eGFRcys slope (β = 0.011, 95% confidence interval [CI] 0.002-0.020). Moreover, higher levels of CRF were significantly associated with a lower risk of rapid kidney function decline (odds ratio, 0.86; 95% CI, 0.75-0.99). These associations were not observed when creatinine-based eGFR was used. CONCLUSIONS: In individuals with preserved kidney function, higher levels of CRF were associated with a slower subsequent age-related decline in kidney function, suggesting a potential protective role of CRF.