Analysis of Leukocyte Recruitment in Continuous Veno-Venous Hemofiltration with Regional Citrate vs. Systemic Heparin Anticoagulation

Cells. 2022 Jun 1;11(11):1815. doi: 10.3390/cells11111815.


Acute kidney injury (AKI) is a frequent complication in critically ill patients. Supportive treatment of AKI patients is based on renal-replacement therapy, including continuous veno-venous hemofiltration (CVVH). To limit clotting events on extracorporeal surfaces, anticoagulants are administered, including systemic heparin and local citrate. The differential and comparative effects of these anticoagulants on leukocyte function in acute kidney injury patients are, so far, insufficiently understood. In this bio-add-on-study, AKI patients were randomized as part of a parallel-group trial to either systemic heparin or regional citrate anticoagulation. Patient samples were collected upon inclusion, prior to CVVH initiation at day 0, day 1, day 3 and day 5, following CVVH initiation, and one day after cessation of CVVH, then immediately analyzed. Flow cytometric assessment of surface-receptor molecules was conducted. Whole-blood-perfused human microfluidic chambers were used for the analysis of neutrophil rolling and adhesion. Acute kidney injury was associated with significant changes in the surface expression of CD182 and CD16 throughout CVVH treatment, independent of the anticoagulation regime. AKI furthermore abrogated selectin-induced slow leukocyte rolling and diminished chemokine-induced leukocyte arrest. Subgroup analyses of citrate vs. heparin treatment showed no significant differences between groups, independent of the duration of CVVH treatment. CD182 and CD16 expression remained low in both groups throughout CVVH therapy. These data confirm that AKI impairs selectin-mediated leukocyte slow rolling and chemokine-induced leukocyte arrest in vitro. Systemic heparin or local citrate anticoagulation have no differential effect on the leukocyte recruitment steps examined in this study.

Keywords: CVVH; acute kidney injury; anticoagulation; citrate; heparin; inflammation; leukocytes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury* / therapy
  • Anticoagulants / pharmacology
  • Anticoagulants / therapeutic use
  • Citrates / pharmacology
  • Citrates / therapeutic use
  • Citric Acid / pharmacology
  • Continuous Renal Replacement Therapy*
  • Hemofiltration* / adverse effects
  • Heparin / pharmacology
  • Heparin / therapeutic use
  • Humans
  • Leukocytes


  • Anticoagulants
  • Citrates
  • Citric Acid
  • Heparin

Grants and funding

This research was supported by the German Research Foundation (ZA 428/10-1, ZA 428/21-1, KFO 342/1) and the interdisciplinary center for clinical research of the University of Münster (IZKF Münster, SEED 12/18).