Exercise as a therapeutic option for acute kidney injury: mechanisms and considerations for the design of future clinical studies

Abstract

Acute kidney injury (AKI) is a known risk factor for chronic kidney disease (CKD) and end stage kidney disease (ESKD). The progression from AKI to CKD, despite being well recognised, is not completely understood, although sustained inflammation and fibrosis are implicated. A therapeutic intervention targeting the post AKI stage could reduce the progression to CKD, which has high levels of associated morbidity and mortality. Exercise has known anti-inflammatory effects with animal AKI models demonstrating its use as a therapeutic agent in abrogating renal injury. This suggests the use of an exercise rehabilitation programme in AKI patients following discharge could attenuate renal damage and improve long term patient outcomes. In this review article we outline considerations for future clinical studies of exercise in the AKI population.

Effects of Different Types of Exercise on Kidney Diseases

“…There is conflicting evidence on the effect of exercise on the biochemical factors related to kidney function and the exact mechanism by which exercise may be beneficial in CKD patients. That being said, the well-known anti-inflammatory response of exercise could be its most crucial effect in these patients [ 87 ], since kidney inflammation is prevalent in renal injury [ 88 ], which ultimately causes fibrosis and the everlasting loss of function [ 89 ]. The mechanism for the strong anti-inflammatory effect of exercise is visceral fat reduction, which decreases the secretion of pro-inflammatory adipokines [ 87 ] and increases levels of anti-inflammatory cytokines (interleukin-6 (IL-6), from contracting skeletal muscle) [ 87 ].…”

“…An increase in IL-6 levels slows the rise in tumor necrosis factor-alpha (TNF-a) levels after exposure to an inflammatory stimulus [ 90 ]. The exercise-induced rise in IL-6 and the simultaneous reduction in TNF-a levels proposes the potential therapeutic effect of exercise in controlling low-grade inflammation, which can deteriorate CKD [ 89 ]. In fact, inflammation, insulin resistance, oxidative stress, and an overactive renin-angiotensin system preserve each other while negatively affecting endothelial and cardiovascular function and health [ 91 ].…”

Post-COVID-19 rehabilitation: a special look at chronic kidney disease patients

“…It is known that CKD is associated with the concomitant development of cardiopulmonary diseases, resulting in poor cardiorespiratory fitness and all its deleterious consequences [ 27 ]. Lifestyle changes, medication adequacy, health education, and a rehabilitation program with therapeutic exercises can alleviate kidney damage and improve patient outcomes in the long term [ 2 ]. The aim of rehabilitation in the context of cardiopulmonary complications of SARS-CoV-2 is to trigger the systemic antioxidant response to modulate the inflammatory state generated by the virus and to intervene in the endothelial dysfunction caused by it.…”

Unlocking the Role of Exercise on CD4+ T Cell Plasticity

“…Exercise can improve the efficacy of certain cancer therapies targeting kidney ( 1 ), bladder, testicular, and head and neck cancers ( 2 ). Moreover, exercise alone can improve the outcomes for individuals with diseases including cardiovascular ( 3 ), kidney disease ( 4 , 5 ) and diabetes ( 6 ). It appears that the mechanism(s) underlying the benefits of exercise on disease outcomes is related to augmentation of cytokine profiles, however, there is little known about the involvement of immune cells in this process.…”