Shanmugakumar Chinnappa1,2, Nigel Lewis3, Omer Baldo4, Ming-Chieh Shih5, Yu-Kang Tu5, Andrew Mooney2,6. 1. Department of Nephrology, Doncaster and Bassetlaw Teaching Hospitals National Health Service Trust, Doncaster, United Kingdom shanmugakumar.chinnappa@nhs.net. 2. Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom. 3. Department of Cardiology, Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield, United Kingdom. 4. Department of Urology, Airedale National Health Service Foundation Trust, Keighley, United Kingdom. 5. Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan. 6. Department of Nephrology, Leeds Teaching Hospitals National Health Service Trust, Leeds, United Kingdom.
Abstract
BACKGROUND: 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. METHODS: 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 (VO2peak) 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. RESULTS: Compared with healthy controls, in patients with CKD, the VO2peak was impaired proportionate to its severity. Peak cardiac output was the predominant determinant of VO2peak in healthy controls and patients with heart failure, whereas C(a-v)O2 played a more significant role in determining VO2peak 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. CONCLUSIONS: In CKD, both peak cardiac output and peak C(a-v)O2 are independent predictors of VO2peak, and the more significant roleplayed by peak C(a-v)O2 highlights the importance of noncardiac factors in determining exercise capacity in CKD.
BACKGROUND: 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. METHODS: 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 (VO2peak) 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. RESULTS: Compared with healthy controls, in patients with CKD, the VO2peak was impaired proportionate to its severity. Peak cardiac output was the predominant determinant of VO2peak in healthy controls and patients with heart failure, whereas C(a-v)O2 played a more significant role in determining VO2peak 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. CONCLUSIONS: In CKD, both peak cardiac output and peak C(a-v)O2 are independent predictors of VO2peak, and the more significant roleplayed by peak C(a-v)O2 highlights the importance of noncardiac factors in determining exercise capacity in CKD.
Authors: Bryan Kestenbaum; Jorge Gamboa; Sophia Liu; Amir S Ali; Eric Shankland; Thomas Jue; Cecilia Giulivi; Lucas R Smith; Jonathan Himmelfarb; Ian H de Boer; Kevin Conley; Baback Roshanravan Journal: JCI Insight Date: 2020-03-12
Authors: Janani Rangaswami; Vivek Bhalla; John E A Blair; Tara I Chang; Salvatore Costa; Krista L Lentine; Edgar V Lerma; Kenechukwu Mezue; Mark Molitch; Wilfried Mullens; Claudio Ronco; W H Wilson Tang; Peter A McCullough Journal: Circulation Date: 2019-04-16 Impact factor: 29.690
Authors: Alexander Nelson; James Otto; John Whittle; Robert C M Stephens; Daniel S Martin; John R Prowle; Gareth L Ackland Journal: Open Heart Date: 2016-02-24