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

Kenneth Lim,Gordon Mcgregor,Gregory D Lewis,Sharon M Moe,Andrew R Coggan

doi:10.3389/fphys.2020.572355

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.

Highlights

Cardiovascular disease is a modern-day global epidemic (Kwan and Benjamin, 2015)
Allows imaging of extent of regional wall motion responses to stress; has better accuracy for detecting significant coronary stenosis ranging from 80 to 90% compared to exercise EKG Well-validated and multiple studies have shown incremental prognostic utility over clinical data for demonstrating resting and stress-induced regional WMA Can detect scar pattern and burden, presence of subendocardial scar by delayed enhancement on Cardiac Magnetic Resonance Imaging (CMR) has been associated with coronary artery disease (CAD) risk factors, depressed LV ejection fraction and severe CAD on angiography Well validated prognostic tool in Chronic Kidney Disease (CKD); high prevalence of perfusion defects in end-stage kidney disease (ESKD) patients
Among the patients with VT ≥ 40%, survival did not differ significantly between those who were transplanted and those who were not. These results suggest that assessment of VT using Cardiopulmonary Exercise Testing (CPET) can provide a high level of discrimination to risk stratify patients for timely kidney transplantation, and that those with a VT < 40% may benefit from early transplantation

Summary

INTRODUCTION

Cardiovascular disease is a modern-day global epidemic (Kwan and Benjamin, 2015). Over the past century, our world has witnessed a striking epidemiologic transition in the predominant cause of death, from communicable diseases and nutritional deficiencies to non-communicable diseases (Nascimento et al, 2014). It has become clear that resting cardiac and pulmonary function testing cannot reliably predict exercise performance and functional capacity, and that overall health status is more strongly associated with exercise tolerance than with resting measurements (Albouaini et al, 2007) This understanding, together with the principle that the fundamental role of the cardiovascular system is to function as an effective oxygen transport system, provides the rationale for the assessment of oxygen uptake (VO2) at maximal or peak exercise (VO2Peak) as a robust, objective and reproducible index of cardiovascular functional capacity. Lessons learned from the Fick equation, as applied to the complex systemic changes that occur with declining kidney function, demand that we look beyond cardiac or vascular changes alone, toward an integrative viewpoint when assessing overall cardiovascular health status in CKD patients rather than static single-organ measures. Breathing frequency Tidal volume Minute ventilation Maximum voluntary ventilation mmHg mmHg – l l min− 1 l l.min− 1 l.min− 1

O2 peak

Summary

Findings

CONCLUSION AND FUTURE DIRECTIONS