Cardiac and Noncardiac Determinants of Exercise Capacity in CKD

Impaired exercise capacity is a significant symptom of CKD and is associated with poor survival. Furthermore, there is a growing interest in applying exercise as a diagnostic tool or as therapy in CKD. However, an in-depth understanding of exercise physiology in CKD is still lacking.

To evaluate the role of cardiac (central) and noncardiac (peripheral) determinants of exercise capacity in CKD, we conducted a cross-sectional study of 70 male patients with CKD (stages 2-5) without diabetes or cardiac disease, 35 healthy controls, and 25 patients with heart failure. An integrated cardiopulmonary exercise test using a CO₂ rebreathing technique was used to measure peak O₂ consumption (VO_2peak) and peak cardiac output simultaneously, and to calculate peak peripheral O₂ extraction (C[a-v]O₂), the peripheral determinant (the ability of exercising skeletal muscles to extract oxygen). We performed multiple regression analysis and used Bayesian information criteria (BIC) changes to quantitatively assess the individual contribution of central and peripheral factors.

Compared with healthy controls, in patients with CKD, the VO_2peak was impaired proportionate to its severity. Peak cardiac output was the predominant determinant of VO_2peak in healthy controls and patients with heart failure, whereas C(a-v)O₂ played a more significant role in determining VO_2peak in CKD (β=0.68, P<0.001) compared with cardiac output (β=0.63, P<0.001). In addition, the magnitude of BIC reduction was greater for C(a-v)O₂ compared with cardiac output (BIC, 298.72 versus 287.68) in CKD.

In CKD, both peak cardiac output and peak C(a-v)O₂ are independent predictors of VO_2peak, and the more significant roleplayed by peak C(a-v)O₂ highlights the importance of noncardiac factors in determining exercise capacity in CKD.