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Open Access Highly Accessed Research article

Citrate confers less filter-induced complement activation and neutrophil degranulation than heparin when used for anticoagulation during continuous venovenous haemofiltration in critically ill patients

Louise Schilder1, S Azam Nurmohamed1, Pieter M ter Wee1, Nanne J Paauw2, Armand RJ Girbes3, Albertus Beishuizen3, Robert HJ Beelen2 and AB Johan Groeneveld4*

Author Affiliations

1 Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands

2 Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands

3 Department of Intensive Care, VU University Medical Center, Amsterdam, The Netherlands

4 Department of Intensive Care, Erasmus Medical Center, Rotterdam, The Netherlands

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BMC Nephrology 2014, 15:19  doi:10.1186/1471-2369-15-19

Published: 17 January 2014

Abstract

Background

During continuous venovenous haemofiltration (CVVH), regional anticoagulation with citrate may be superior to heparin in terms of biocompatibility, since heparin as opposed to citrate may activate complement (reflected by circulating C5a) and induce neutrophil degranulation in the filter and myeloperoxidase (MPO) release from endothelium.

Methods

No anticoagulation (n = 13), unfractionated heparin (n = 8) and trisodium citrate (n = 17) regimens during CVVH were compared. Blood samples were collected pre- and postfilter; C5a, elastase and MPO were determined by ELISA. Additionally, C5a was also measured in the ultrafiltrate.

Results

In the heparin group, there was C5a production across the filter which most decreased over time as compared to other groups (P = 0.007). There was also net production of elastase and MPO across the filter during heparin anticoagulation (P = 0.049 or lower), while production was minimal and absent in the no anticoagulation and citrate group, respectively. During heparin anticoagulation, plasma concentrations of MPO at the inlet increased in the first 10 minutes of CVVH (P = 0.024).

Conclusion

Citrate confers less filter-induced, potentially harmful complement activation and neutrophil degranulation and less endothelial activation than heparin when used for anticoagulation during continuous venovenous haemofiltration in critically ill patients.

Keywords:
Acute kidney injury; Biocompatibility; Citrate; Complement activation; Critically ill patients; Elastase; Heparin; MPO; Neutrophils; Renal replacement therapy