Exercise intolerance in kidney diseases: physiological contributors and therapeutic strategies

Abstract

Exertional fatigue, defined as the overwhelming and debilitating sense of sustained exhaustion that impacts the ability to perform activities of daily living, is highly prevalent in chronic kidney disease (CKD) and end-stage renal disease (ESRD). Subjective reports of exertional fatigue are paralleled by objective measurements of exercise intolerance throughout the spectrum of the disease. The prevalence of exercise intolerance is clinically noteworthy, as it leads to increased frailty, worsened quality of life, and an increased risk of mortality. The physiological underpinnings of exercise intolerance are multifaceted and still not fully understood. This review aims to provide a comprehensive outline of the potential physiological contributors, both central and peripheral, to kidney disease-related exercise intolerance and highlight current and prospective interventions to target this symptom. In this review, the CKD-related metabolic derangements, cardiac and pulmonary dysfunction, altered physiological responses to oxygen consumption, vascular derangements, and sarcopenia are discussed in the context of exercise intolerance. Lifestyle interventions to improve exertional fatigue, such as aerobic and resistance exercise training, are discussed, and the lack of dietary interventions to improve exercise tolerance is highlighted. Current and prospective pharmaceutical and nutraceutical strategies to improve exertional fatigue are also broached. An extensive understanding of the pathophysiological mechanisms of exercise intolerance will allow for the development of more targeted therapeutic approached to improve exertional fatigue and health-related quality of life in CKD and ESRD.

Cardiorespiratory fitness in kidney transplant recipients compared to patients with kidney failure: a systematic review and meta‐analysis

“…Exercise intolerance appears as an important feature of CKD that is present even in patients with early CKD stages and rises exponentially with the progression to advanced stages and end-stage kidney disease [3]. Exercise intolerance was previously shown to be closely correlated with reduced QOL [3] and to be independently associated with cardiovascular events and death in this population [4][5][6].…”

“…Several factors have been suggested to affect the complex associations between CKD and associated QOL decrease, including significant changes in physical and mental functioning that lead to a vicious cycle of inactivity, deconditioning, social isolation, and depression [2]. Exercise intolerance appears as an important feature of CKD that is present even in patients with early CKD stages and rises exponentially with the progression to advanced stages and end-stage kidney disease [3]. Exercise intolerance was previously shown to be closely correlated with reduced QOL [3] and to be independently associated with cardiovascular events and death in this population [4][5][6].…”

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

“…As long as the activity intensity levels remain light to moderate, aerobic metabolism effectively matches the energy demand [36]. High intensity exercise, though, is limited by the capacity of aerobic metabolism and often results in VO 2 rising to its most tolerable limit, due to symptom-related fatigue that causes the individual to stop the activity [37].…”

“…Furthermore, in patients with chronic respiratory disorders, mechanical constrains of ventilation is another important cause of exercise limitation, since produced respiratory discomfort may limit exercise capacity before actual physiological limitation occurs [39]. Exercise intolerance is highly prevalent in CKD and is associated with increased frailty, worsened quality of life, and high risk of hospitalization and mortality [37]. The mechanisms of exercise intolerance in CKD appear to be a complex interaction between central and peripheral factors, including kidney disease-related metabolic derangements, cardiac and pulmonary dysfunction, altered physiologic responses to oxygen consumption, vascular derangement, abnormal neurocirculatory control, and sarcopenia.…”

“…These central and peripheral factors may result in exercise limitation, principally of circulatory etiology, via several mechanisms, such as deconditioning, anemia, uncontrolled hypertension, sarcopenia, and heart failure, creating one or more distinct CPET patterns, which permit prioritization of contributing factors. However, these abnormalities remain to be fully elucidated, particularly in the non-dialysis CKD population [37].…”