Filtration of Macrophage Migration Inhibitory Factor (MIF) in Patients with End Stage Renal Disease Undergoing Hemodialysis.

Peter Luedike,Werner Kleophas,Julia Pohl,Ulrike Hendgen-Cotta,Matthias Totzeck,Malte Kelm,Martin Heisler,Tienush Rassaf,Christos Rammos,Gerd R Hetzel,Marc W Merx

doi:10.1371/journal.pone.0140215

Peter Luedike, Werner Kleophas + Show 9 more

Open Access

https://doi.org/10.1371/journal.pone.0140215

Copy DOI

Journal: PloS one	Publication Date: Oct 20, 2015
Citations: 8	License type: CC BY 4.0

Abstract

BackgroundEnd stage renal disease (ESRD) patients are characterized by increased morbidity and mortality due to highest prevalence of cardiovascular disease. Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that controls cellular signaling in human physiology, pathophysiology, and diseases. Increased MIF plasma levels promote vascular inflammation and development of atherosclerosis. We have shown that MIF is associated with vascular dysfunction in ESRD patients. Whether hemodialysis (HD) affects circulating MIF plasma levels is unknown. We here aimed to investigate whether HD influences the circulating MIF pool in ESRD patients.Methods and ResultsAn observational single-center study was conducted. MIF plasma levels in ESRD patients were assessed before, during, and after a HD session (n = 29). Healthy age-matched volunteers served as controls to compare correlations of MIF plasma levels with inflammatory plasma components (n = 20). MIF removed from the circulating blood pool could be detected in the dialysate and allowed for calculation of totally removed MIF (MIF content in dialysate 219±4 μg/HD-session). MIF plasma levels were markedly decreased 2 hour after initiation of HD (MIF plasma level pre-HD 84.8±6 ng/ml to intra-HD 61.2±5 ng/ml p<0.001) and were replenished already 20 min after termination of HD to basal levels (intra-HD 61.2±5 ng/ml to post-HD 79.8±5 ng/ml, p<0.001).ConclusionMIF is a dialyzable plasma component that is effectively filtrated during HD from the patient blood pool in large amounts. After removal of remarkable amounts of MIF during a single HD session, MIF plasma pool is early reconstituted after termination of HD from unknown sources.

Highlights

Patients with end stage renal disease (ESRD) are at the highest risk for the development of cardiovascular events like stroke or myocardial infarction and suffer from increased morbidity and mortality.[1,2,3] Sustained vascular inflammation is the cornerstone of increased cardiovascular risk in End stage renal disease (ESRD) patients.[4], Hemodialysis (HD) per se influences inflammatory processes in patients under maintenance HD.[5]
We have shown that migration inhibitory factor (MIF) is associated with vascular dysfunction in ESRD patients
Healthy age-matched volunteers served as controls to compare correlations of MIF plasma levels with inflammatory plasma components (n = 20)

Summary

Introduction

Patients with end stage renal disease (ESRD) are at the highest risk for the development of cardiovascular events like stroke or myocardial infarction and suffer from increased morbidity and mortality.[1,2,3] Sustained vascular inflammation is the cornerstone of increased cardiovascular risk in ESRD patients.[4], Hemodialysis (HD) per se influences inflammatory processes in patients under maintenance HD.[5] This influences vascular functions, which are blunted in ESRD and after HD.[6, 7] In patients with ESRD, MIF plasma levels are associated with diminished endothelial function and increased vascular stiffness and correlate with myocardial injury.[8] ESRD goes along with systemic inflammation and is associated with increased platelet activation.[9] The impact of HD therapy on circulating MIF levels in ESRD patients has not been investigated so far. Increased MIF plasma levels promote vascular inflammation and development of atherosclerosis. We here aimed to investigate whether HD influences the circulating MIF pool in ESRD patients

Methods

Results

Conclusion