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

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.

Anticoagulation in hemodialysis: A narrative review

“…However, the reported failure rates were high for both the heparin‐coated membranes and saline flush/predilution protocol (31.5% and 49.6%, respectively) 121 . Dialysis efficiency and clotting events were not reported in this study, and the ECC was flushed with heparinized saline prior to treatment 129 . Overall, use of a heparin‐coated dialyzer may be superior to saline flushes alone, 21,118,121 but appears less effective than other heparin‐sparing modalities 130,131 .…”

“…121 Dialysis efficiency and clotting events were not reported in this study, and the ECC was flushed with heparinized saline prior to treatment. 129 Overall, use of a heparin-coated dialyzer may be superior to saline flushes alone, 21,118,121 but appears less effective than other heparin-sparing modalities. 130,131 Routine use of coated dialyzers would likely require either circuit priming with an anticoagulant or systemic anticoagulation to be sustainable.…”

Monocytes as Targets for Immunomodulation by Regional Citrate Anticoagulation

“…In addition to chemotactic properties, this cytokine has significant pleiotropic effects on the immune system, ranging from monocyte activation and priming to infection to cell differentiation [ 30 ]. The depletion of plasma levels of MCP-1 during heparin-free hemodialysis has already been described elsewhere, even though an HD session with systemic heparinization usually increases MCP-1 levels [ 31 , 32 ].…”

Impact of CRRT in Patients with PARDS Treated with VV-ECMO

“…Another cause of hemodynamic instability may be related to an alteration in the segmental kinetics of the left ventricle that can occur in the early hours of CRRT; this is described in adults and remains controversial [ 34 ]. A third potential cause is the exposure of blood to two artificial membranes resulting in the release of cytokines which can in turn induce vasoplegia [ 35 ]. A final etiology may be the release of hemoglobin and ATP following hemolysis resulting from shear stress generated by differences in flow velocity.…”