Baseline and usual cardiorespiratory fitness and the risk of chronic kidney disease: A prospective study and meta-analysis of published observational cohort studies

Chronic kidney disease (CKD) is a global public health burden but is largely preventable. Few studies have reported an association between high levels of cardiorespiratory fitness (CRF) and decreased risk of CKD. However, some relevant aspects of the association, such as the dose-response relationship and the long-term relevance of CRF levels to CKD, have yet to be addressed. We, therefore, aimed to quantify the nature and magnitude of the association between CRF and CKD in a cohort of 2099 men aged 42-61 years with normal kidney function at baseline. CRF was directly measured using a respiratory gas exchange analyzer during cardiopulmonary exercise testing. Hazard ratios (HRs) (95% CIs) were estimated for the incidence of CKD. Correction for within-person variability was made using data from repeat measurements of CRF taken 11 years after baseline. A total of 197 CKD events were recorded during a median follow-up of 25.8 years. The age-adjusted regression dilution ratio for CRF was 0.59 (95% CI: 0.53-0.65). The risk of CKD decreased in a graded fashion with increasing CRF. Comparing extreme tertiles of CRF, the HR (95% CI) for CKD was 0.67 (0.46-0.97) following adjustment for several established and emerging risk factors. The corresponding adjusted HR (95% CI) was 0.51 (0.27-0.96) following correction for within-person variability. In a meta-analysis of five population-based cohort studies (including the current study) comprising 32,447 participants and 4,043 CKD cases, the fully-adjusted risk ratios (95% CIs) for CKD comparing extreme tertiles of baseline and long-term CRF values were 0.58 (0.46-0.73) and 0.40 (0.27-0.59), respectively. Findings from a new prospective study and pooled analysis of previous studies plus the new study indicate that high CRF levels are strongly and independently associated with a reduced risk of CKD and consistent with a linear dose-response relationship. Using single baseline measurements of CRF to investigate the association between CRF and CKD risk could considerably underestimate the true association.