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Open Access 01-04-2014 | Research

The plasma level and biomarker value of neutrophil gelatinase-associated lipocalin in critically ill patients with acute kidney injury are not affected by continuous venovenous hemofiltration and anticoagulation applied

Authors: Louise Schilder, S Azam Nurmohamed, Pieter M ter Wee, Nanne J Paauw, Armand RJ Girbes, Albertus Beishuizen, Robert HJ Beelen, AB Johan Groeneveld

Published in: Critical Care | Issue 2/2014

Abstract

Introduction

Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury (AKI), and levels reflect severity of disease in critically ill patients. However, continuous venovenous hemofiltration (CVVH) may affect plasma levels by clearance or release of NGAL by activated neutrophils in the filter, dependent on the anticoagulation regimen applied. We therefore studied handling of NGAL by CVVH in patients with AKI.

Methods

Immediately before initiation of CVVH, prefilter blood was drawn. After 10, 60, 180, and 720 minutes of CVVH, samples were collected from pre- and postfilter (in- and outlet) blood and ultrafiltrate. CVVH with the following anticoagulation regimens was studied: no anticoagulation in case of a high bleeding tendency (n = 13), unfractionated heparin (n = 8), or trisodium citrate (n = 21). NGAL levels were determined with enzyme-linked immunosorbent assay (ELISA).

Results

Concentrations of NGAL at inlet and outlet were similar, and concentrations did not change over time in any of the anticoagulation groups; thus no net removal or production of NGAL occurred. Concentrations of NGAL at inlet correlated with disease severity at initiation of CVVH and at the end of a CVVH run. Concentrations of NGAL in the ultrafiltrate were lower with citrate-based CVVH (P = 0.03) and decreased over time, irrespective of anticoagulation administered (P < 0.001). The sieving coefficient and clearance of NGAL were low and decreased over time (P < 0.001).

Conclusions

The plasma level and biomarker value of NGAL in critically ill patients with AKI are not affected by CVVH, because clearance by the filter was low. Furthermore, no evidence exists for intrafilter release of NGAL by neutrophils, irrespective of the anticoagulation method applied.

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Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C: Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005, 294: 813-818. 10.1001/jama.294.7.813CrossRefPubMed

Kjeldsen L, Bainton DF, Sengeløv H, Borregaard N: Identification of neutrophil gelatinase-associated lipocalin as a novel matrix protein of specific granules in human neutrophils. Blood 1994, 83: 799-807.PubMed

Paragas N, Qiu A, Zhang Q, Samstein B, Deng SX, Schmidt-Ott KM, Viltard M, Yu W, Forster CS, Gong G, Liu Y, Kulkarni R, Mori K, Kalandadze A, Ratner AJ, Devarajan P, Landry DW, D'Agati V, Lin CS, Barasch J: The Ngal reporter mouse detects the response of the kidney to injury in real time. Nat Med 2011, 17: 216-222. 10.1038/nm.2290PubMedCentralCrossRefPubMed

Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P: Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 2005, 365: 1231-1238. 10.1016/S0140-6736(05)74811-XCrossRefPubMed

Kümpers P, Hafer C, Lukasz A, Lichtinghagen R, Brand K, Fliser D, Faulhaber-Walter R, Kielstein JT: Serum neutrophil gelatinase-associated lipocalin at inception of renal replacement therapy predicts survival in critically ill patients with acute kidney injury. Crit Care 2010, 14: R9. 10.1186/cc8861PubMedCentralCrossRefPubMed

Cruz DN, de Cal M, Garzotto F, Perazella MA, Lentini P, Corradi V, Piccinni P, Ronco C: Plasma neutrophil gelatinase-associated lipocalin is an early biomarker for acute kidney injury in an adult ICU population. Intensive Care Med 2010, 36: 444-451. 10.1007/s00134-009-1711-1PubMedCentralCrossRefPubMed

de Geus HR, Bakker J, Lesaffre EM, le Noble JL: Neutrophil gelatinase-associated lipocalin at ICU admission predicts for acute kidney injury in adult patients. Am J Respir Crit Care Med 2011, 183: 907-914. 10.1164/rccm.200908-1214OCCrossRefPubMed

Soto K, Papoila AL, Coelho S, Bennett M, Ma Q, Rodrigues B, Fidalgo P, Frade F, Devarajan P: Plasma NGAL for the diagnosis of AKI in patients admitted from the Emergency Department setting. Clin J Am Soc Nephrol 2013, 8: 2053-2063. 10.2215/CJN.12181212PubMedCentralCrossRefPubMed

Hjortrup PB, Haase N, Wetterslev M, Perner A: Clinical review: predictive value of neutrophil gelatinase-associated lipocalin for acute kidney injury in intensive care patients. Crit Care 2013, 17: 211. 10.1186/cc11855PubMedCentralCrossRefPubMed

10.

Haase M, Bellomo R, Devarajan P, Schlattmann P, Haase-Fielitz A: Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis 2009, 54: 1012-1024. 10.1053/j.ajkd.2009.07.020CrossRefPubMed

11.

Bagshaw SM, Bennett M, Haase M, Haase-Fielitz A, Egi M, Morimatsu H, D'amico G, Goldsmith D, Devarajan P, Bellomo R: Plasma and urine neutrophil gelatinase-associated lipocalin in septic versus non-septic acute kidney injury in critical illness. Intensive Care Med 2010, 36: 452-461. 10.1007/s00134-009-1724-9CrossRefPubMed

12.

Srisawat N, Murugan R, Lee M, Kong L, Carter M, Angus DC, Kellum JA: Plasma neutrophil gelatinase-associated lipocalin predicts recovery from acute kidney injury following community-acquired pneumonia. Kidney Int 2011, 80: 545-552. 10.1038/ki.2011.160PubMedCentralCrossRefPubMed

13.

Mårtensson J, Bell M, Oldner A, Xu S, Venge P, Martling CR: Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury. Intensive Care Med 2010, 36: 1333-1340. 10.1007/s00134-010-1887-4CrossRefPubMed

14.

Kim H, Hur M, Cruz DN, Moon HW, Yun YM: Plasma neutrophil gelatinase-associated lipocalin as a biomarker for acute kidney injury in critically ill patients with suspected sepsis. Clin Biochem 2013, 46: 1414-1418. 10.1016/j.clinbiochem.2013.05.069CrossRefPubMed

15.

Otto GP, Busch M, Sossdorf M, Claus RA: Impact of sepsis-associated cytokine storm on plasma NGAL during acute kidney injury in a model of polymicrobial sepsis. Crit Care 2013, 17: 419. 10.1186/cc12540PubMedCentralCrossRefPubMed

16.

Bobek I, Gong D, De Cal M, Cruz D, Chionh CY, Haapio M, Soni SS, Nalesso F, Lentini P, Garzotto F, Corradi V, Ronco C: Removal of neutrophil gelatinase-associated lipocalin by extracorporeal therapies. Hemodial Int 2010, 14: 302-307. 10.1111/j.1542-4758.2010.00452.xCrossRefPubMed

17.

de Geus HR, Betjes MG, Bakker J: Neutrophil gelatinase-associated lipocalin clearance during veno-venous continuous renal replacement therapy in critically ill patients. Intensive Care Med 2010, 36: 2156-2157. 10.1007/s00134-010-2015-1PubMedCentralCrossRefPubMed

18.

Malyszko J, Malyszko JS, Koc-Zorawska E, Kozminski P, Mysliwiec M: Neutrophil gelatinase-associated lipocalin in dialyzed patients is related to residual renal function, type of renal replacement therapy and inflammation. Kidney Blood Press Res 2009, 32: 464-469. 10.1159/000274048CrossRefPubMed

19.

Jönsson P, Ståhl ML, Ohlsson K: Extracorporeal circulation causes release of neutrophil gelatinase-associated lipocalin (NGAL). Mediators Inflamm 1999, 8: 169-171. 10.1080/09629359990504PubMedCentralCrossRefPubMed

20.

Tiranathanagul K, Jearnsujitwimol O, Susantitaphong P, Kijkriengkraikul N, Leelahavanichkul A, Srisawat N, Praditpornsilpa K, Eiam-Ong S: Regional citrate anticoagulation reduces polymorphonuclear cell degranulation in critically ill patients treated with continuous venovenous hemofiltration. Ther Apher Dial 2011, 15: 556-564. 10.1111/j.1744-9987.2011.00996.xCrossRefPubMed

21.

Schilder L, Nurmohamed SA, Ter Wee PM, Paauw NJ, Girbes AR, Beishuizen A, Beelen RH, Groeneveld AJ: 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. 10.1186/1471-2369-15-19PubMedCentralCrossRefPubMed

22.

Nurmohamed SA, Vervloet MG, Girbes AR, Ter Wee PM, Groeneveld AB: Continuous venovenous hemofiltration with or without predilution regional citrate anticoagulation: a prospective study. Blood Purif 2007, 25: 316-323. 10.1159/000107045CrossRefPubMed

23.

Schilder L, Nurmohamed SA, ter Wee PM, Girbes AR, Beishuizen A, Paauw NJ, Beelen RH, Groeneveld AB: Effect of anticoagulation regimens on handling of interleukin-6 and −8 during continuous venovenous hemofiltration in critically ill patients with acute kidney injury. Cytokine 2012, 60: 601-607. 10.1016/j.cyto.2012.08.015CrossRefPubMed

24.

Bos JC, Grooteman MP, van Houte AJ, Schoorl M, van Limbeek J, Nubé MJ: Low polymorphonuclear cell degranulation during citrate anticoagulation: a comparison between citrate and heparin dialysis. Nephrol Dial Transplant 1997, 12: 1387-1393. 10.1093/ndt/12.7.1387CrossRefPubMed

Title: The plasma level and biomarker value of neutrophil gelatinase-associated lipocalin in critically ill patients with acute kidney injury are not affected by continuous venovenous hemofiltration and anticoagulation applied
Authors: Louise Schilder
S Azam Nurmohamed
Pieter M ter Wee
Nanne J Paauw
Armand RJ Girbes
Albertus Beishuizen
Robert HJ Beelen
AB Johan Groeneveld
Publication date: 01-04-2014
Publisher: BioMed Central
Published in: Critical Care / Issue 2/2014
Electronic ISSN: 1364-8535
DOI: https://doi.org/10.1186/cc13838

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The plasma level and biomarker value of neutrophil gelatinase-associated lipocalin in critically ill patients with acute kidney injury are not affected by continuous venovenous hemofiltration and anticoagulation applied

Abstract

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

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