Kidney Dysfunction, Cardiorespiratory Fitness, and the Risk of Death in Women

Background: Chronic kidney disease (CKD) is associated with increased risk of cardiovascular (CV) events and death. However, the effect of cardiorespiratory fitness on the CKD-mortality relationship remains unknown, particularly in women. Methods: We used Cox regression to estimate hazard ratios (HR) for the effect of kidney function and fitness on all-cause mortality in a prospective cohort of 5716 women free of CKD and CV disease symptoms. Serum creatinine (Cr) was used to estimate glomerular filtration rate (eGFR), and spot urine protein and maximal stress tests were performed at baseline. Results: Mean age at baseline was 52.5 +/- 10.8 years, and 86% of the sample was Caucasian. Mean Cr was 1.11 +/- 0.14 mg/dL, and mean eGFR was 53.7 +/- 8.3 mL/min/1.73m(2) at baseline. The mean follow-up was 15.9 +/- 2.2 years, with 589 deaths identified. Cr < 1.4 was associated with an HR of death of 1.59 (p=0.03). After adjustment for traditional CV risk factors and fitness, the risk of death decreased by 3% (p<0.001) for every mL/min/1.73m(2) increase in eGFR. Compared to women with an eGFR <45mL/min/1.73m(2), the risk of death was reduced by 36% and 47%, for eGFR 45-59.9mL/min/1.73m(2) and eGFR >= 60mL/min/1.73m(2), respectively (p<0.001). At every level of eGFR, fitness remained an independent predictor of mortality, with the lowest level of fitness (<5 metabolic equivalents [METs]) at the highest risk of mortality regardless of eGFR level. Conclusions: Fitness remains an independent predictor of mortality regardless of eGFR. eGFR was a stronger predictor of mortality compared to Cr or the presence of proteinuria. These findings have important implications for clinical practice and health policy, as the level of cardiorespiratory fitness predicts risk of death in the presence of asymptomatic CKD.