Impairment of Cardiovascular Functional Capacity in Mild to Moderate Kidney Dysfunction

Abstract

Background: Traditional diagnostic tools that assess resting cardiac function and structure fail to accurately reflect cardiovascular alterations in patients with chronic kidney disease (CKD). This study sought to determine whether multidimensional exercise response patterns related to cardiovascular functional capacity can detect abnormalities in mild-to-moderate CKD.

Methods: In a cross-sectional study, we examined 3,075 participants from the Framingham Heart Study (FHS) and 451 participants from the Massachusetts General Hospital Exercise Study (MGH-ExS) who underwent cardiopulmonary exercise testing (CPET). Participants were stratified by estimated glomerular filtration rate (eGFR): eGFR ≥90; eGFR 60-89; eGFR 30-59. Our primary outcomes of interest were peak oxygen uptake (VO2Peak),VO2 at anaerobic threshold (VO2AT), and the ratio of minute ventilation to carbon dioxide production (VE/VCO2). Multiple linear regression models were fitted to evaluate the associations between eGFR group and each outcome variable adjusted for covariates.

Results: In the FHS cohort, N=1,712 (56%) had an eGFR ≥90 ml/min/1.73m2, N=1,271 (41%) had an eGFR 60-89 ml/min/1.73m2, and N=92 (3%) had an eGFR 30-59 ml/min/1.73m2. In the MGH-ExS cohort, N=247 (55%) had an eGFR ≥90 ml/min/1.73m2, N=154 (34%) had an eGFR 60-89 ml/min/1.73m2, and N=50 (11%) had an eGFR 30-59 ml/min/1.73m2. In FHS, VO2Peak and VO2AT were incrementally impaired with declining kidney function (p<0.001); however this pattern was attenuated following adjustment for age. Percent-predicted VO2Peak at AT was higher in the lower eGFR groups (p<0.001). In MGH-ExS, VO2Peak and VO2AT were incrementally impaired with declining kidney function in unadjusted and adjusted models (p<0.05). VO2Peak was associated with eGFR (p<0.05) in all models even after adjusting for age. On further mechanistic analysis, we directly measured cardiac output (CO) at peak exercise via right heart catheterization and found impaired CO in the lower eGFR groups (p≤0.007).

Conclusion: CPET-derived indices may detect impairment in cardiovascular functional capacity and track cardiac output declines in mild to moderate CKD.