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Published in: BMC Nephrology 1/2024

Open Access 01-12-2024 | Acute Kidney Injury | Research

Longitudinal NGAL and cystatin C plasma profiles present a high level of heterogeneity in a mixed ICU population

Authors: Daniela Jou-Valencia, Meint Volbeda, Jan G. Zijlstra, Jenny E Kootstra-Ros, Jill Moser, Matijs van Meurs, Jacqueline Koeze

Published in: BMC Nephrology | Issue 1/2024

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Abstract

Background

NGAL and Cystatin C (CysC) as biomarkers for the early detection of AKI are subject to both pathophysiological, as well as patient related heterogeneity. The aim of this study was to investigate the timeline of plasma levels of NGAL and CysC during the first seven days of ICU admission in a mixed ICU population and to relate these to AKI severity during ICU stay. Via these means we aimed to bring clarity to the previously reported heterogeneity of these renal biomarkers.

Methods

Prospective Observation Cohort. Consecutive patients admitted to adult ICU at an academic hospital in the Netherlands between 18-02-2014 and 31-03-2014 were included. Urine output, serum creatinine, plasma NGAL and CysC were recorded during the first seven days of ICU admission. Biomarker expression was analyzed based on KDIGO score and time of AKI diagnosis.

Results

335 patients were included, 110 met KDIGO criteria for AKI. NGAL and CysC plasma levels were higher in AKI patients compared to non-AKI, high variability in individual values resulted in 56% of AKI patients having a false negative, and 32% of non-AKI patients having a false positive. Individual biomarker levels were variable, and no pattern based on KDIGO score was observed.

Conclusions

Plasma NGAL and CysC as biomarkers for the early AKI detection may be subject to pathophysiological, and patient related heterogeneity. Further understanding of individual biomarker profiles may help in their application amongst mixed ICU populations.

Trial Registration

The need for informed consent was waived by the Institutional Ethical Review Board of the University Medical Center Groningen (METc 2013 − 174) by Prof. dr. W.A. Kamps on May 17th 2013.
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Literature
1.
go back to reference Koeze J, Keus F, Dieperink W, Van der Horst ICC, Zijlstra JG, Van Meurs M. Incidence, timing and outcome of AKI in critically ill patients varies with the definition used and the addition of urine output criteria. BMC Nephrol. 2017;18(1):70.CrossRefPubMedPubMedCentral Koeze J, Keus F, Dieperink W, Van der Horst ICC, Zijlstra JG, Van Meurs M. Incidence, timing and outcome of AKI in critically ill patients varies with the definition used and the addition of urine output criteria. BMC Nephrol. 2017;18(1):70.CrossRefPubMedPubMedCentral
3.
go back to reference Schrezenmeier EV, Barasch J, Budde K, Westhoff T, Schmidt-Ott KM. Biomarkers in acute kidney injury - pathophysiological basis and clinical performance. Acta Physiol. 2017;219(3):556–74.CrossRef Schrezenmeier EV, Barasch J, Budde K, Westhoff T, Schmidt-Ott KM. Biomarkers in acute kidney injury - pathophysiological basis and clinical performance. Acta Physiol. 2017;219(3):556–74.CrossRef
4.
go back to reference Kellum JA, Romagnani P, Ashuntantang G, Ronco C, Zarbock A, Anders HJ. Acute kidney injury. Volume 7. Nature Reviews Disease Primers. Nature Research; 2021. Kellum JA, Romagnani P, Ashuntantang G, Ronco C, Zarbock A, Anders HJ. Acute kidney injury. Volume 7. Nature Reviews Disease Primers. Nature Research; 2021.
5.
go back to reference Kellum JA, Lameire N, Aspelin P, Barsoum RS, Burdmann EA, Goldstein SL, et al. Kidney disease: improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury. Kidney International Supplements. Volume 2. Nature Publishing Group; 2012. pp. 1–138. Kellum JA, Lameire N, Aspelin P, Barsoum RS, Burdmann EA, Goldstein SL, et al. Kidney disease: improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury. Kidney International Supplements. Volume 2. Nature Publishing Group; 2012. pp. 1–138.
6.
go back to reference Flannery AH, Bosler K, Ortiz-Soriano V, Gianella F, Prado V, Toto RD, et al. Kidney biomarkers and major adverse kidney events in critically ill patients. Kidney360. 2020;2(1):26–32.CrossRefPubMedPubMedCentral Flannery AH, Bosler K, Ortiz-Soriano V, Gianella F, Prado V, Toto RD, et al. Kidney biomarkers and major adverse kidney events in critically ill patients. Kidney360. 2020;2(1):26–32.CrossRefPubMedPubMedCentral
7.
go back to reference Jou-Valencia D, Koeze J, Popa ER, Aslan A, Zwiers PJ, Molema G, et al. Heterogenous Renal Injury Biomarker Production reveals Human Sepsis-Associated Acute kidney Injury subtypes. Crit Care Explor. 2019;1(10):e0047.CrossRefPubMedPubMedCentral Jou-Valencia D, Koeze J, Popa ER, Aslan A, Zwiers PJ, Molema G, et al. Heterogenous Renal Injury Biomarker Production reveals Human Sepsis-Associated Acute kidney Injury subtypes. Crit Care Explor. 2019;1(10):e0047.CrossRefPubMedPubMedCentral
8.
go back to reference De Geus HRH, Betjes MG, Van Schaick R, Groeneveld JABJ. Plasma NGAL similarly predicts acute kidney injury in sepsis and nonsepsis. Biomark Med. 2013;7(3):415–21.CrossRefPubMed De Geus HRH, Betjes MG, Van Schaick R, Groeneveld JABJ. Plasma NGAL similarly predicts acute kidney injury in sepsis and nonsepsis. Biomark Med. 2013;7(3):415–21.CrossRefPubMed
9.
go back to reference Herget-Rosenthal S, Marggraf G, Hüsing J, Göring F, Pietruck F, Janssen O, et al. Early detection of acute renal failure by serum cystatin C. Kidney Int. 2004;66(3):1115–22.CrossRefPubMed Herget-Rosenthal S, Marggraf G, Hüsing J, Göring F, Pietruck F, Janssen O, et al. Early detection of acute renal failure by serum cystatin C. Kidney Int. 2004;66(3):1115–22.CrossRefPubMed
10.
go back to reference Hall PS, Mitchell ED, Smith AF, Cairns DA, Messenger M, Hutchinson M et al. Meta-analysis of diagnostic tests for acute kidney injury. 2018. Hall PS, Mitchell ED, Smith AF, Cairns DA, Messenger M, Hutchinson M et al. Meta-analysis of diagnostic tests for acute kidney injury. 2018.
11.
go back to reference Meersch M, Schmidt C, Hoffmeier A, Van Aken H, Wempe C, Gerss J, et al. Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: the PrevAKI randomized controlled trial. Intensive Care Med. 2017;43(11):1551–61.CrossRefPubMedPubMedCentral Meersch M, Schmidt C, Hoffmeier A, Van Aken H, Wempe C, Gerss J, et al. Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: the PrevAKI randomized controlled trial. Intensive Care Med. 2017;43(11):1551–61.CrossRefPubMedPubMedCentral
12.
go back to reference Spahillari A, Parikh CR, Sint K, Koyner JL, Patel UD, Edelstein CL, et al. Serum cystatin C- versus creatinine-based definitions of acute kidney injury following cardiac surgery: a prospective cohort study. Am J Kidney Dis. 2012;60(6):922–9.CrossRefPubMedPubMedCentral Spahillari A, Parikh CR, Sint K, Koyner JL, Patel UD, Edelstein CL, et al. Serum cystatin C- versus creatinine-based definitions of acute kidney injury following cardiac surgery: a prospective cohort study. Am J Kidney Dis. 2012;60(6):922–9.CrossRefPubMedPubMedCentral
13.
go back to reference Koeze J, van der Horst ICC, Keus F, Wiersema R, Dieperink W, Kootstra-Ros JE, et al. Plasma neutrophil gelatinase-associated lipocalin at intensive care unit admission as a predictor of acute kidney injury progression. Clin Kidney J. 2020;13(6):994–1002.CrossRefPubMedPubMedCentral Koeze J, van der Horst ICC, Keus F, Wiersema R, Dieperink W, Kootstra-Ros JE, et al. Plasma neutrophil gelatinase-associated lipocalin at intensive care unit admission as a predictor of acute kidney injury progression. Clin Kidney J. 2020;13(6):994–1002.CrossRefPubMedPubMedCentral
14.
go back to reference Haase M, Bellomo R, Devarajan P, Schlattmann P, Haase-Fielitz A, Bagshaw SM, et al. 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(6):1012–24.CrossRefPubMed Haase M, Bellomo R, Devarajan P, Schlattmann P, Haase-Fielitz A, Bagshaw SM, et al. 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(6):1012–24.CrossRefPubMed
15.
go back to reference Albert C, Zapf A, Haase M, Röver C, Pickering JW, Albert A, et al. Neutrophil Gelatinase-Associated Lipocalin measured on Clinical Laboratory platforms for the prediction of Acute kidney Injury and the Associated need for Dialysis Therapy: a systematic review and Meta-analysis. Am J Kidney Dis. 2020;76(6):826–841e1.CrossRefPubMedPubMedCentral Albert C, Zapf A, Haase M, Röver C, Pickering JW, Albert A, et al. Neutrophil Gelatinase-Associated Lipocalin measured on Clinical Laboratory platforms for the prediction of Acute kidney Injury and the Associated need for Dialysis Therapy: a systematic review and Meta-analysis. Am J Kidney Dis. 2020;76(6):826–841e1.CrossRefPubMedPubMedCentral
16.
go back to reference 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. Volume 17. Critical Care: BioMed Central; 2013. p. 211. 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. Volume 17. Critical Care: BioMed Central; 2013. p. 211.
17.
go back to reference Yong Z, Pei X, Zhu B, Yuan H, Zhao W. Predictive value of serum cystatin C for acute kidney injury in adults: a meta-analysis of prospective cohort trials. Sci Rep. 2017;7(1):1–11.CrossRef Yong Z, Pei X, Zhu B, Yuan H, Zhao W. Predictive value of serum cystatin C for acute kidney injury in adults: a meta-analysis of prospective cohort trials. Sci Rep. 2017;7(1):1–11.CrossRef
19.
go back to reference Bagshaw SM, Rewa O, Bagshaw SM. Acute kidney injury—epidemiology, outcomes and economics. Nat Publishing Group. 2014;10(10). Bagshaw SM, Rewa O, Bagshaw SM. Acute kidney injury—epidemiology, outcomes and economics. Nat Publishing Group. 2014;10(10).
20.
go back to reference Mårtensson J, Bellomo R. The rise and fall of NGAL in Acute kidney Injury. Blood Purif. 2014;37(4):304–10.CrossRefPubMed Mårtensson J, Bellomo R. The rise and fall of NGAL in Acute kidney Injury. Blood Purif. 2014;37(4):304–10.CrossRefPubMed
21.
go back to reference Albert C, Haase M, Albert A, Zapf A, Braun-Dullaeus RC, Haase-Fielitz A. Biomarker-guided Risk Assessment for Acute kidney Injury: time for clinical implementation? Vol. 41, annals of Laboratory Medicine. Seoul National University, Institute for Cognitive Science; 2020. pp. 1–15. Albert C, Haase M, Albert A, Zapf A, Braun-Dullaeus RC, Haase-Fielitz A. Biomarker-guided Risk Assessment for Acute kidney Injury: time for clinical implementation? Vol. 41, annals of Laboratory Medicine. Seoul National University, Institute for Cognitive Science; 2020. pp. 1–15.
22.
go back to reference Vanmassenhove J, Van Biesen W, Vanholder R, Lameire N. Subclinical AKI: ready for primetime in clinical practice? Journal of Nephrology. Volume 32. Springer International Publishing; 2019. pp. 9–16. Vanmassenhove J, Van Biesen W, Vanholder R, Lameire N. Subclinical AKI: ready for primetime in clinical practice? Journal of Nephrology. Volume 32. Springer International Publishing; 2019. pp. 9–16.
23.
go back to reference Wiersema R, Jukarainen S, Eck RJ, Kaufmann T, Koeze J, Keus F et al. Different applications of the KDIGO criteria for AKI lead to different incidences in critically ill patients: a post hoc analysis from the prospective observational SICS-II study. Crit Care. 2020;24(1). Wiersema R, Jukarainen S, Eck RJ, Kaufmann T, Koeze J, Keus F et al. Different applications of the KDIGO criteria for AKI lead to different incidences in critically ill patients: a post hoc analysis from the prospective observational SICS-II study. Crit Care. 2020;24(1).
24.
go back to reference Haase M, Devarajan P, Haase-Fielitz A, Bellomo R, Cruz DN, Wagener G et al. The outcome of Neutrophil Gelatinase-Associated Lipocalin-positive subclinical acute kidney Injury: a Multicenter pooled analysis of prospective studies. J Am Coll Cardiol. 2011. Haase M, Devarajan P, Haase-Fielitz A, Bellomo R, Cruz DN, Wagener G et al. The outcome of Neutrophil Gelatinase-Associated Lipocalin-positive subclinical acute kidney Injury: a Multicenter pooled analysis of prospective studies. J Am Coll Cardiol. 2011.
25.
go back to reference McCullough PA, Shaw AD, Haase M, Bouchard J, Waikar SS, Siew ED et al. Diagnosis of Acute Kidney Injury Using Functional and Injury Biomarkers: Workgroup Statements from the Tenth Acute Dialysis Quality Initiative Consensus Conference. In: Contributions to Nephrology. Karger Publishers; 2013. p. 13–29. McCullough PA, Shaw AD, Haase M, Bouchard J, Waikar SS, Siew ED et al. Diagnosis of Acute Kidney Injury Using Functional and Injury Biomarkers: Workgroup Statements from the Tenth Acute Dialysis Quality Initiative Consensus Conference. In: Contributions to Nephrology. Karger Publishers; 2013. p. 13–29.
26.
go back to reference Göcze I, Jauch D, Götz M, Kennedy P, Jung B, Zeman F, et al. Biomarker-guided intervention to prevent Acute kidney Injury after major surgery. Ann Surg. 2018;267(6):1013–20.CrossRefPubMed Göcze I, Jauch D, Götz M, Kennedy P, Jung B, Zeman F, et al. Biomarker-guided intervention to prevent Acute kidney Injury after major surgery. Ann Surg. 2018;267(6):1013–20.CrossRefPubMed
27.
go back to reference Bouchard J. Estimating baseline serum creatinine for assessing Acute kidney Injury: not a one size fits all Approach. Kidney Int Rep. 2021;6(3):562–4.CrossRefPubMedPubMedCentral Bouchard J. Estimating baseline serum creatinine for assessing Acute kidney Injury: not a one size fits all Approach. Kidney Int Rep. 2021;6(3):562–4.CrossRefPubMedPubMedCentral
Metadata
Title
Longitudinal NGAL and cystatin C plasma profiles present a high level of heterogeneity in a mixed ICU population
Authors
Daniela Jou-Valencia
Meint Volbeda
Jan G. Zijlstra
Jenny E Kootstra-Ros
Jill Moser
Matijs van Meurs
Jacqueline Koeze
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2024
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-024-03477-2

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