Critical Care Nephrology – Research Article
Kaewdoungtien P.a,b,c· Tachaboon S.b,c· Kangsumrith N.b,c· Srisawat N.b,c,d,e,faDivision of Nephrology, Department of Medicine, Police General Hospital, Royal Thai Police Headquarters, Bangkok, Thailand
bDivision of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
cExcellence Center for Critical Care Nephrology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
dCenter of Excellence in Critical Care Nephrology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
eAcademy of Science, Royal Society of Thailand, Bangkok, Thailand
fTropical Medicine Cluster, Chulalongkorn University, Bangkok, Thailand
Log in to MyKarger to check if you already have access to this content.
Buy FullText & PDF Unlimited re-access via MyKarger Unrestricted printing, no saving restrictions for personal use read more
CHF 38.00 *
EUR 35.00 *
USD 39.00 *
Buy a Karger Article Bundle (KAB) and profit from a discount!
If you would like to redeem your KAB credit, please log in.
Save over 20% compared to the individual article price. Rent via DeepDyve Unlimited fulltext viewing of this article Organize, annotate and mark up articles Printing and downloading restrictions apply Subscribe Access to all articles of the subscribed year(s) guaranteed for 5 years Unlimited re-access via Subscriber Login or MyKarger Unrestricted printing, no saving restrictions for personal use read more Select* The final prices may differ from the prices shown due to specifics of VAT rules.
Article / Publication DetailsFirst-Page Preview
Received: August 02, 2022
Accepted: January 20, 2023
Published online: March 14, 2023
Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 3
ISSN: 0253-5068 (Print)
eISSN: 1421-9735 (Online)
For additional information: https://www.karger.com/BPU
AbstractIntroduction: Acute kidney injury (AKI) is a common syndrome in critically ill patients. Continuous renal replacement therapy (CRRT) is the standard treatment for patients with AKI. Research on the immunomodulating effects of regional citrate anticoagulation (RCA) remains limited in patients with AKI receiving CRRT. We aimed to evaluate the immunomodulating effects of RCA in patients with AKI receiving CRRT. Methods: A randomized controlled trial study on critically ill adult patients with AKI undergoing CRRT was undertaken. Participants were randomized into either a regional citrate group or control group (either heparin anticoagulant or normal saline). Measurements were taken at baseline, 6 and 24 h after commencing CRRT for CD11b expression, C3a, C5a, and plasminogen activator inhibitor-1 (PAI-1) levels. Clinical outcomes assessed were 28-day survival rate, length of ICU stay, renal support duration, and renal function at discharge. Results: Thirty patients were recruited and randomized into 2 groups of 15 subjects. Baseline demographic and clinical data were comparable between groups. In the citrate group, CD11b expression was significantly decreased at 24 h compared to the control group (1.84% [1.18–3.32] versus 4.92% [2.63–6.93], p < 0.01). The complement level, including c3b and c5a, was stable during CRRT. Additionally, the PAI-1 levels were significantly decreased at 24 h compared to the control group (114 ng/mL [19–193] versus 359 ng/mL [264–491], p < 0.01). No significant difference in survival rate was observed. Conclusions: RCA may have the potential to mitigate the inflammatory response by decreasing CD11b expression of neutrophil and improve fibrinolysis activity through a reduction of PAI-1 levels. Larger clinical trials are warranted to test this immunomodulation effect of RCA.
© 2023 S. Karger AG, Basel
References Wiersema R, Eck RJ, Haapio M, Koeze J, Poukkanen M, Keus F, et al. Burden of acute kidney injury and 90-day mortality in critically ill patients. BMC Nephrol. 2019;21(1):1. Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120(4):c179–84. Ashbrook MJ, McDonough KL, Pituch JJ, Christopherson PL, Cornell TT, Selewski DT, et al. Citrate modulates lipopolysaccharide-induced monocyte inflammatory responses. Clin Exp Immunol. 2015;180(3):520–30. Phillipson M, Heit B, Colarusso P, Liu L, Ballantyne CM, Kubes P. Intraluminal crawling of neutrophils to emigration sites: a molecularly distinct process from adhesion in the recruitment cascade. J Exp Med. 2006;203(12):2569–75. Klos A, Tenner AJ, Johswich KO, Ager RR, Reis ES, Kohl J. The role of the anaphylatoxins in health and disease. Mol Immunol. 2009;46(14):2753–66. Morrow GB, Whyte CS, Mutch NJ. A Serpin with a finger in many PAIs: PAI-1’s central function in thromboinflammation and cardiovascular disease. Front Cardiovasc Med. 2021;8:653655. Wang ZH, Ren WY, Zhu L, Hu LJ. Plasminogen activator inhibitor-1 regulates LPS induced inflammation in rat macrophages through autophagy activation. ScientificWorldJournal. 2014;2014:189168. Bos JC, Grooteman MP, van Houte AJ, Schoorl M, van Limbeek J, Nube MJ. Low polymorphonuclear cell degranulation during citrate anticoagulation: a comparison between citrate and heparin dialysis. Nephrol Dial Transpl. 1997;12(7):1387–93. Hernandez MR, Galan AM, Lozano M, Bozzo J, Cases A, Escolar G, et al. Platelet-leukocyte activation during hemodialysis detected with a monoclonal antibody to leukocyte integrin CD11b. Nephron. 1998;80(2):197–203. Shukla P, Rao GM, Pandey G, Sharma S, Mittapelly N, Shegokar R, et al. Therapeutic interventions in sepsis: current and anticipated pharmacological agents. Br J Pharmacol. 2014;171(22):5011–31. Fang F, Zhang Y, Tang J, Lunsford LD, Li T, Tang R, et al. Association of corticosteroid treatment with outcomes in adult patients with sepsis: a systematic review and meta-analysis. JAMA Intern Med. 2019;179(2):213–23. Lamers C, Pluss CJ, Ricklin D. The promiscuous profile of complement receptor 3 in ligand binding, immune modulation, and pathophysiology. Front Immunol. 2021;12:662164. Ruchaud-Sparagano MH, Stocks SC, Turley H, Dransfield I. Activation of neutrophil function via CD66: differential effects upon beta 2 integrin mediated adhesion. Br J Haematol. 1997;98(3):612–20. Muller Kobold AC, Tulleken JE, Zijlstra JG, Sluiter W, Hermans J, Kallenberg CG, et al. Leukocyte activation in sepsis; correlations with disease state and mortality. Intensive Care Med. 2000;26(7):883–92. Dalal PJ, Muller WA, Sullivan DP. Endothelial cell calcium signaling during barrier function and inflammation. Am J Pathol. 2020;190(3):535–42. Charchaflieh J, Wei J, Labaze G, Hou YJ, Babarsh B, Stutz H, et al. The role of complement system in septic shock. Clin Dev Immunol. 2012;2012:407324. Dhondt A, Vanholder R, Tielemans C, Glorieux G, Waterloos MA, De Smet R, et al. Effect of regional citrate anticoagulation on leukopenia, complement activation, and expression of leukocyte surface molecules during hemodialysis with unmodified cellulose membranes. Nephron. 2000;85(4):334–42. Schilder L, Nurmohamed SA, ter Wee PM, Paauw NJ, Girbes ARJ, Beishuizen A, et al. Citrate confers less filter-induced complement activation and neutrophil degranulation than heparin when used for anticoagulation during continuous venovenous haemofiltration in critically ill patients. BMC Nephrol. 2014;15:19. Bohler J, Schollmeyer P, Dressel B, Dobos G, Horl WH. Reduction of granulocyte activation during hemodialysis with regional citrate anticoagulation: dissociation of complement activation and neutropenia from neutrophil degranulation. J Am Soc Nephrol. 1996;7(2):234–41. Pandey M, Loskutoff DJ, Samad F. Molecular mechanisms of tumor necrosis factor-alpha-mediated plasminogen activator inhibitor-1 expression in adipocytes. FASEB J. 2005;19(10):1317–9. Rega G, Kaun C, Weiss TW, Demyanets S, Zorn G, Kastl SP, et al. Inflammatory cytokines interleukin-6 and oncostatin m induce plasminogen activator inhibitor-1 in human adipose tissue. Circulation. 2005;111(15):1938–45. Madoiwa S, Nunomiya S, Ono T, Shintani Y, Ohmori T, Mimuro J, et al. Plasminogen activator inhibitor 1 promotes a poor prognosis in sepsis-induced disseminated intravascular coagulation. Int J Hematol. 2006;84(5):398–405. Yamamoto C, Kaji T, Sakamoto M, Kozuka H, Koizumi F. Calcium regulation of tissue plasminogen activator and plasminogen activator inhibitor-1 release from cultured human vascular endothelial cells. Thromb Res. 1994;74(2):163–8. Tipoe TL, Wu WKK, Chung L, Gong M, Dong M, Liu T, et al. Plasminogen activator inhibitor 1 for predicting sepsis severity and mortality outcomes: a systematic review and meta-analysis. Front Immunol. 2018;9:1218. Tiranathanagul K, Jearnsujitwimol O, Susantitaphong P, Kijkriengkraikul N, Leelahavanichkul A, Srisawat N, et al. Regional citrate anticoagulation reduces polymorphonuclear cell degranulation in critically ill patients treated with continuous venovenous hemofiltration. Ther Apher Dial. 2011;15(6):556–64. Fisher R, Moore GW, Mitchell MJ, Dai L, Crichton S, Lumlertgul N, et al. Effects of regional citrate anticoagulation on thrombin generation, fibrinolysis and platelet function in critically ill patients receiving continuous renal replacement therapy for acute kidney injury: a prospective study. Ann Intensive Care. 2022;12(1):29. Oudemans-van Straaten HM, Kellum JA, Bellomo R. Clinical review: anticoagulation for continuous renal replacement therapy: heparin or citrate? Crit Care. 2011;15(1):202. Lappegard KT, Fung M, Bergseth G, Riesenfeld J, Lambris JD, Videm V, et al. Effect of complement inhibition and heparin coating on artificial surface-induced leukocyte and platelet activation. Ann Thorac Surg. 2004;77(3):932–41. Oudemans-van Straaten HM, Ostermann M. Bench-to-bedside review: citrate for continuous renal replacement therapy, from science to practice. Crit Care. 2012;16(6):249. Liu C, Mao Z, Kang H, Hu J, Zhou F. Regional citrate versus heparin anticoagulation for continuous renal replacement therapy in critically ill patients: a meta-analysis with trial sequential analysis of randomized controlled trials. Crit Care. 2016;20(1):144. Zarbock A, Kullmar M, Kindgen-Milles D, Wempe C, Gerss J, Brandenburger T, et al. Effect of regional citrate anticoagulation vs systemic heparin anticoagulation during continuous kidney replacement therapy on dialysis filter life span and mortality among critically ill patients with acute kidney injury: a randomized clinical trial. JAMA. 2020;324(16):1629–39. Article / Publication DetailsFirst-Page Preview
Received: August 02, 2022
Accepted: January 20, 2023
Published online: March 14, 2023
Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 3
ISSN: 0253-5068 (Print)
eISSN: 1421-9735 (Online)
For additional information: https://www.karger.com/BPU
Copyright / Drug Dosage / Disclaimer Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Comments (0)