Cardiovascular Functional Changes in Chronic Kidney Disease: Integrative Physiology, Pathophysiology and Applications of Cardiopulmonary Exercise Testing

Abstract

The development of cardiovascular disease during renal impairment involves striking multi-tiered, multi-dimensional complex alterations encompassing the entire oxygen transport system. Complex interactions between target organ systems involving alterations of the heart, vascular, musculoskeletal and respiratory systems occur in Chronic Kidney Disease (CKD) and collectively contribute to impairment of cardiovascular function. These systemic changes have challenged our diagnostic and therapeutic efforts, particularly given that imaging cardiac structure at rest, rather than ascertainment under the stress of exercise, may not accurately reflect the risk of premature death in CKD. The multi-systemic nature of cardiovascular disease in CKD patients provides strong rationale for an integrated approach to the assessment of cardiovascular alterations in this population. State-of-the-art cardiopulmonary exercise testing (CPET) is a powerful, dynamic technology that enables the global assessment of cardiovascular functional alterations and reflects the integrative exercise response and complex machinery that form the oxygen transport system. CPET provides a wealth of data from a single assessment with mechanistic, physiological and prognostic utility. It is an underutilized technology in the care of patients with kidney disease with the potential to help advance the field of cardio-nephrology. This article reviews the integrative physiology and pathophysiology of cardio-renal impairment, critical new insights derived from CPET technology, and contemporary evidence for potential applications of CPET technology in patients with kidney disease.

Assessment of Exercise Intolerance in Patients with Pre-Dialysis CKD with Cardiopulmonary Function Testing: Translation to Everyday Practice

“…As discussed above, exercise limitation in patients with CKD can be attributed to a wide variety of coexisting disorders of the cardiac, respiratory, nervous, and muscular systems that can be directly or indirectly linked with reduced renal function [18, 19]. As CPET is the optimal tool in the differential diagnosis of conditions associated with reduced cardiovascular reserve, it may help towards the identification of previously “hidden” causes of poor exercise capacity in patients with pre-dialysis CKD, such as respiratory functional disturbances and neuromuscular disorders [69]. Moreover, CPET use, through discrimination of the underlying causes of physical impairment and exertional fatigue in CKD patients, who suffer from multiple comorbidities, may facilitate treatment optimization towards symptom relief and functional capacity improvement.…”

“…As of this writing, trials in other patient populations (i.e., individuals with heart failure) have used CPET parameters as intermediate cardiovascular endpoints [78, 79]. On this basis, using comprehensive CPET end points could be a valid option also for cardiorenal outcome trials [69]; for this to happen, long-term and optimally designed studies should first evaluate the association of key CPET parameters, such as VO 2 peak, with key outcomes such as cardiovascular and all-cause mortality specifically in patients with CKD.…”

FGF23 and Cardiovascular Structure and Function in Advanced Chronic Kidney Disease

“…However, the effects of these latter single measures of structural or morphologic alterations and their coupling to cardiovascular performance and functional intolerance are largely unknown. 14 This has made it difficult to accurately determine the role and potential utility of FGF23 as a biomarker for assessing cardiovascular functional performance in patients with CKD.…”

Cardiopulmonary exercise testing to observe subclinical abnormalities in cardiopulmonary function in patients undergoing peritoneal dialysis

“…CPET is a powerful dynamic test that can be used to comprehensively assess cardiovascular function and exercise capacity. CPET also provides an index of gas metabolism that facilitates the assessment of organ systems that restrict gas transport; thus, this technique has significant advantages over the 6‐min walk test in assessing exercise capacity (Lim et al, 2020). The use of CPET is based on the principle that resting cardiopulmonary function tests cannot predict performance and functional reserve during exercise and that overall health status is better correlated with exercise tolerance ("ATS/A CCP Statement on cardiopulmonary exercise testing, 2003).…”