Exercise during hemodialysis does not affect the phenotype or prothrombotic nature of microparticles but alters their proinflammatory function.

Naomi Martin,Nicolette C Bishop,Maurice R Dungey,Alice C Smith,James O Burton,Hannah M L Young

doi:10.14814/phy2.13825

Abstract

Hemodialysis patients have dysfunctional immune systems, chronic inflammation and comorbidity‐associated risks of cardiovascular disease (CVD) and infection. Microparticles are biologically active nanovesicles shed from activated endothelial cells, immune cells, and platelets; they are elevated in hemodialysis patients and are associated with chronic inflammation and predictive of CVD mortality in this group. Exercise is advocated in hemodialysis to improve cardiovascular health yet acute exercise induces an increase in circulating microparticles in healthy populations. Therefore, this study aimed to assess acute effect of intradialytic exercise (IDE) on microparticle number and phenotype, and their ability to induce endothelial cell reactive oxygen species (ROS) in vitro. Eleven patients were studied during a routine hemodialysis session and one where they exercised in a randomized cross‐over design. Microparticle number increased during hemodialysis (2064–7071 microparticles/μL, P < 0.001) as did phosphatidylserine+ (P < 0.05), platelet‐derived (P < 0.01) and percentage procoagulant neutrophil‐derived microparticles (P < 0.05), but this was not affected by IDE. However, microparticles collected immediately and 60 min after IDE (but not later) induced greater ROS generation from cultured endothelial cells (P < 0.05), suggesting a transient proinflammatory event. In summary IDE does not further increase prothrombotic microparticle numbers that occurs during hemodialysis. However, given acute proinflammatory responses to exercise stimulate an adaptation toward a circulating anti‐inflammatory environment, microparticle‐induced transient increases of endothelial cell ROS in vitro with IDE may indicate the potential for a longer‐term anti‐inflammatory adaptive effect. These findings provide a crucial evidence base for future studies of microparticles responses to IDE in view of the exceptionally high risk of CVD in these patients.

Highlights

Chronic kidney disease (CKD) affects approximately 10% of the world’s population (Eckardt et al 2013)
We have recently reported favorable changes in inflammatory leukocyte phenotype with a reduction in monocytes with a proinflammatory phenotype in patients after 6 months of moderate intensity intradialytic exercise (IDE) compared with non-exercising HD patients (Dungey et al 2017)
Evaluation of the effects of hemodialysis and IDE on total and prothrombotic microparticles We observed a significant increase in the number of MP over the course of HD (Fig. 2) with a ~4 fold increase from 60 min into HD compared to the end of HD

Summary

Introduction

Chronic kidney disease (CKD) affects approximately 10% of the world’s population (Eckardt et al 2013). Patients with end-stage renal disease have a dysfunctional immune system that is paradoxically chronically activated and anergic (Betjes 2013); this manifests as systemic inflammation associated with an increased risk of atherosclerosis, cardiovascular disease (CVD), and cachexia (Stenvinkel 2010; Heine et al 2012). End-stage renal disease patients are immunologically vulnerable (Kurts et al 2013) and have higher risk and greater severity of infections and associated tissue injury (Dalrymple and Go 2008). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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