Impairment of Cardiovascular Functional Capacity in Mild-to-Moderate Kidney Dysfunction

Abstract

Key Points:

1. Mild-to-moderate CKD is associated with impairment in cardiovascular functional capacity as assessed by oxygen uptake at peak exercise (VO₂Peak).

2. Cardiac output is significantly reduced in patients with mild-to-moderate CKD and is associated with impaired VO₂Peak.

3. Assessment of VO₂Peak by cardiopulmonary exercise testing can detect decrements in cardiovascular function during early stages of kidney function decline that may not be captured using resting left ventricular geometric indices alone.

Background: Traditional diagnostic tools that assess resting cardiac function and structure fail to accurately reflect cardiovascular alterations in patients with 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 3075 participants from the Framingham Heart Study (FHS) and 451 participants from the Massachusetts General Hospital Exercise Study (MGH-ExS) who underwent cardiopulmonary exercise testing. Participants were stratified by eGFR: eGFR ≥90, eGFR 60–89, and eGFR 30–59. Our primary outcomes of interest were peak oxygen uptake (VO₂Peak), VO₂ at anaerobic threshold (VO₂AT), and 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, 1712 participants (56%) had an eGFR ≥90 ml/min per 1.73 m², 1271 (41%) had an eGFR of 60–89 ml/min per 1.73 m², and 92 (3%) had an eGFR of 30–59 ml/min per 1.73 m². In the MGH-ExS cohort, 247 participants (55%) had an eGFR ≥90 ml/min per 1.73 m², 154 (34%) had an eGFR of 60–89 ml/min per 1.73 m², and 50 (11%) had an eGFR of 30–59 ml/min per 1.73 m². In FHS, VO₂Peak and VO₂AT were incrementally impaired with declining kidney function (P < 0.001); however, this pattern was attenuated after 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 by right heart catheterization and found impaired CO in the lower eGFR groups (P ≤ 0.007).

Conclusions: Cardiopulmonary exercise testing–derived indices may detect impairment in cardiovascular functional capacity and track CO declines in mild-to-moderate CKD.

Graphical abstract

Figure 1

Box plots of cardiovascular functional measures for the FHS Cohort. (A) Unadjusted VO₂Peak. (B) Adjusted VO₂Peak. (C) Unadjusted VO₂AT. (D) Adjusted VO₂AT. (E) Unadjusted VE/VCO₂. (F) Adjusted VE/VCO₂. Values were adjusted for sex, height, weight, age, hypertension, diabetes mellitus, and β-blocker use. FHS, Framingham Heart Study; VE/VCO₂, ratio of minute ventilation to carbon dioxide; VO₂AT, oxygen consumption at the point of anaerobic threshold; VO₂Peak, peak oxygen consumption.

Figure 2

Box plots of cardiovascular functional measures for the MGH-ExS cohort. (A) Unadjusted VO₂Peak. (B) Adjusted VO₂Peak. (C) Unadjusted VO₂ at the point of VO₂ AT. (D) Adjusted VO₂ AT. (E) Unadjusted VE/VCO₂. (F) Adjusted VE/VCO₂. Values were adjusted for sex, height, weight, age, hypertension, diabetes mellitus, and β-blocker use. MGH-ExS, Massachusetts General Hospital Exercise Study.

Figure 3

CO in the MGH-ExS cohort. (A) Unadjusted CO. (B) Adjusted CO. Values were adjusted for sex, height, weight, age, hypertension, diabetes mellitus, and β-blocker use. (C) Bivariate regression analysis between eGFR and CO. CO, cardiac output.

Figure 4

Bivariate regression analyses between cardiovascular functional measures and eGFR. Relationship between eGFR and (A) VO₂Peak for the FHS cohort, (B) VO₂ AT for the FHS cohort, (C) VE/VCO₂ for the FHS cohort, (D) VO₂Peak for the MGH-ExS cohort, (E) VO₂ AT for the MGH-ExS cohort, and (F) VE/VCO₂ for the MGH-ExS cohort.