Cardiopulmonary exercise testing reveals subclinical abnormalities in chronic kidney disease

Abstract

Background Reductions in exercise capacity associated with exercise intolerance augment cardiovascular disease risk and predict mortality in chronic kidney disease. This study utilized cardiopulmonary exercise testing to (a) investigate mechanisms of exercise intolerance; (b) unmask subclinical abnormalities that may precede cardiovascular disease in chronic kidney disease. Design The design of this study was cross-sectional. Methods Cardiopulmonary exercise testing was carried out in 31 Stage 3-4 chronic kidney disease patients (60 ± 11 years; estimated glomerular filtration rate 43 ± 13 ml/min/1.73 m) and 21 matched healthy individuals (healthy controls; 56 ± 5 years; estimated glomerular filtration rate>90 ml/min/1.73 m) on a cycle ergometer with workload increased by 15 W every minute until volitional fatigue. Breath-by-breath respiratory gas analysis was performed with an automated gas analyzer and averaged over 10 s intervals. Results Peak oxygen uptake was reduced in chronic kidney disease compared to healthy controls (17.43 ± 1.03 vs 28 ± 2.05 ml/kg/min; p < 0.01), as was oxygen uptake at the ventilatory threshold (9.44 ± 0.53 vs15.55 ± 1.34 ml/kg/min; p < 0.01). A steeper minute ventilation rate/carbon dioxide production slope (32 ± 0.8 vs 28 ± 1; p < 0.01) and a lower expired carbon dioxide pressure in chronic kidney disease (27 ± 0.6 vs 31 ± 0.9 vs 0.9; p < 0.01) indicated ventilation perfusion mismatching in these patients. The ventilatory cost of oxygen uptake was higher in chronic kidney disease (37 ± 0.8 vs 33 ± 1; p < 0.01). Maximum heart rate (134 ± 5 vs 159 ± 3 bpm) and one-minute heart rate recovery (15 ± 1 vs 20 ± 2 bpm) were reduced in chronic kidney disease ( p < 0.01). Conclusion This study suggests that both central and peripheral limitations likely contribute to reduced exercise capacity in non-dialysis chronic kidney disease. Additionally, cardiopulmonary exercise testing revealed subclinical cardiopulmonary abnormalities in these patients in the absence of overt cardiovascular disease. Cardiopulmonary exercise testing could potentially be a tool for unmasking cardiopulmonary abnormalities preceding cardiovascular disease in chronic kidney disease.

Lifestyle Interventions with a Focus on Nutritional Strategies to Increase Cardiorespiratory Fitness in Chronic Obstructive Pulmonary Disease, Heart Failure, Obesity, Sarcopenia, and Frailty

“…Exercise testing in subjects with stage 3-4 CKD has revealed a reduced CRF with altered central and peripheral responses to exercise compared to healthy age matched controls [144]. Furthermore, in subjects with stage 2-4 CKD who performed the 6MWT, those who walked a distance below 350 m versus those above that threshold had a significantly decreased risk of survival [145].…”

“…As recognition of low CRF as a risk factor for morbidity and mortality grows, more knowledge is accrued about the pathogenesis of exercise intolerance in different disease states and CRF is more widely used as an outcome measure. A wide variety of disease states such as chronic kidney disease (CKD), cancer, non-alcoholic steatohepatitis, atrial fibrillation, and pulmonary hypertension are now recognized to be associated with reduced CRF, and all have a role for nutrition therapy that may assist in increasing CRF and improving outcomes [144][145][146][147][148][149].…”

Response of the oxygen uptake efficiency slope to exercise training in patients with chronic kidney disease

“…Baba et al [13] developed an objective, reproducible estimation of cardiorespiratory function called the oxygen uptake efficiency slope (OUES) that does not require a maximal exercise effort and might therefore be useful in populations, such as CKD patients, deemed high risk for maximal exercise testing [7]. The OUES integrates cardiovascular, musculoskeletal, and respiratory function into a single index [14].…”

“…Low cardiorespiratory fitness is strongly associated with early all-cause and cardiovascular-related mortality [ 3 , 4 ] and presents a higher risk of early death than other common risk factors such as diabetes or hypertension [ 5 ]. Compared to the general population, CKD patients demonstrate a large reduction in cardiorespiratory fitness that occurs early in the disease process and declines concomitantly with renal function [ 6 - 8 ]. In patients with CKD, low cardiorespiratory fitness is associated with increased aortic stiffness and left ventricle afterload, poor left ventricle function, and a higher burden of cardiovascular risk [ 8 ], and it is unsurprisingly an independent predictor of early mortality [ 9 , 10 ].…”

“…The OUES integrates cardiovascular, musculoskeletal, and respiratory function into a single index [ 14 ]. Remaining relatively stable across CPET duration, the OUES represents the relationship (and efficiency) between oxygen uptake and total ventilation and provides an indication of cardiorespiratory reserve, so it could be a more pragmatic and safer alternative to maximal exercise testing in high-risk patients [ 7 ]. In patients with heart failure, the OUES has superior independent prognostic value over other commonly reported CPET-derived values such as ⩒O 2peak and the ⩒E/⩒CO 2 slope [ 15 ].…”