Unexpected and striking effect of heparin-free dialysis on cytokine release

Alicja Rydzewska-Rosolowska,Michal Mysliwiec,Ewa Koc-Zorawska,Joanna Gozdzikiewicz-Lapinska,Beata Naumnik,Jacek Borawski

doi:10.1007/s11255-017-1589-8

Abstract

Heparin (both unfractionated and low molecular weight) is not only a potent anticoagulant but also has many pleiotropic effects, some of which are mediated by cytokine release. We compared the effect of hemodialysis (HD) with enoxaparin as an anticoagulant and without systemic anticoagulation (heparin-grafted membrane—Evodial) on the release of monocyte chemoattractant protein 1 (MCP-1), endostatin (ES) and activin A (Act-A). Nineteen stable HD patients were dialyzed with or without heparin, and plasma levels of MCP-1, ES and Act-A were measured after such a dialysis. During HD with Evodial, the intradialytic levels of all three cytokines were 2–3 folds lower. The between-anticoagulant differences were significant over time for all three cytokines: MCP-1 (P < 0.001), ES (P < 0.001) and Act-A (P < 0.001). This striking effect of heparin-free dialysis with Evodial membrane may be beneficial not only because it reduces the possibility of bleeding complications but also because it might reduce proinflammatory cytokine concentration and therefore contribute to the improvement in endothelial function. Further studies are needed to determine whether it has a positive effect on morbidity and mortality of maintenance HD patients.

Highlights

Heparin, both unfractionated (UFH) and low molecular weight (LMWH) is a potent anticoagulant and has many pleiotropic effects, some of which are mediated by cytokine release [1,2,3]
Our study reports unexpected depletion of plasma levels of monocyte chemoattractant protein-1 (MCP-1), endostatin and activin A during heparin-free systemic hemodialysis when compared to standard dialysis with low molecular weight heparin
The effect of Evodial membranes on ES and activin A (Act-A) was to our knowledge not reported before, and the effect on MCP-1 is consistent with data published by Morena et al [18]

Summary

Introduction

Both unfractionated (UFH) and low molecular weight (LMWH) is a potent anticoagulant and has many pleiotropic effects, some of which are mediated by cytokine release [1,2,3]. Hemodialysis (HD), a procedure during which heparin is routinely used, can cause an increase in cytokine levels. It generates an abundance of growth factors, cytokines and other mediators playing an important role in the pathogenesis of many signs, symptoms and complications of end-stage renal disease. To elucidate between the role of heparin and hemodialysis on cytokine profiles, aiming to prove that heparin-free dialysis does not cause cytokine release, we constructed the current study to directly compare the effect of dialysis using Evodial membranes with standard dialysis with LMWH anticoagulation. Microinflammation is practically universally present in all hemodialysis patients. It results from serious disturbances of acquired immunity which are caused by many different factors. Antigen-presenting cells (monocytes) preactivation, overproduction of proinflammatory cytokines (Il-1, Il-6, TNF-α) and deficient T lymphocyte-dependent immune response are causes of frequent infections, malnutrition-inflammation-atherosclerosis (MIA) syndrome, high failure vaccination rates among others [6]

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