Ann Lab Med.  2021 Jul;41(4):357-365. 10.3343/alm.2021.41.4.357.

Predictive Value of Plasma NGAL:Hepcidin-25 for Major Adverse Kidney Events After Cardiac Surgery with Cardiopulmonary Bypass: A Pilot Study

Affiliations
  • 1Medical Faculty, University Clinic for Cardiology and Angiology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
  • 2Diaverum Renal Services, MVZ Potsdam, Potsdam, Germany
  • 3Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
  • 4Department of Nephrology and Endocrinology, Klinikum Ernst von Bergmann, Potsdam, Germany
  • 5Institute for Biometrics and Medical Informatics, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
  • 6Department of Intensive Care, The Austin Hospital, Melbourne, Australia
  • 7Centre for Integrated Critical Care, The University of Melbourne, Melbourne, Australia
  • 8Institute of Laboratory Medicine, Hospital Dessau, Dessau, Germany
  • 9Department of Cardiology, Immanuel Diakonie Bernau, Heart Center Brandenburg, Brandenburg Medical School Theodor Fontane, MHB, Germany
  • 10Institute of Social Medicine and Health Systems Research, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
  • 11Faculty of Health Sciences Brandenburg, Potsdam, Germany

Abstract

Background
Neutrophil gelatinase-associated lipocalin (NGAL) and hepcidin-25 are involved in catalytic iron-related kidney injury after cardiac surgery with cardiopulmonary bypass. We explored the predictive value of plasma NGAL, plasma hepcidin-25, and the plasma NGAL:hepcidin-25 ratio for major adverse kidney events (MAKE) after cardiac surgery.
Methods
We compared the predictive value of plasma NGAL, hepcidin-25, and plasma NGAL:hepcidin-25 with that of serum creatinine (Cr) and urinary output and protein for primary-endpoint MAKE (acute kidney injury [AKI] stages 2 and 3, persistent AKI > 48 hours, acute dialysis, and in-hospital mortality) and secondary-endpoint AKI in 100 cardiac surgery patients at intensive care unit (ICU) admission. We performed ROC curve, logistic regression, and reclassification analyses.
Results
At ICU admission, plasma NGAL, plasma NGAL:hepcidin-25, plasma interleukin-6, and Cr predicted MAKE (area under the ROC curve [AUC]: 0.77, 0.79, 0.74, and 0.74, respectively) and AKI (0.73, 0.89, 0.70, and 0.69). For AKI prediction, plasma NGAL:hepcidin-25 had a higher discriminatory power than Cr (AUC difference 0.26 [95% CI 0.00–0.53]). Urinary output and protein, plasma lactate, C-reactive protein, creatine kinase myocardial band, and brain natriuretic peptide did not predict MAKE or AKI (AUC < 0.70). Only plasma NGAL:hepcidin-25 correctly reclassified patients according to their MAKE and AKI status (category-free net reclassification improvement: 0.82 [95% CI 0.12–1.52], 1.03 [0.29–1.77]). After adjustment to the Cleveland risk score, plasma NGAL:hepcidin-25 ≥ 0.9 independently predicted MAKE (adjusted odds ratio 16.34 [95% CI 1.77–150.49], P = 0.014).
Conclusions
Plasma NGAL:hepcidin-25 is a promising marker for predicting postoperative MAKE.

Keyword

Acute kidney injury; Major adverse kidney events; Cardiac surgery; Cardiopulmonary bypass; Hepcidin; Neutrophil gelatinase-associated lipocalin; Serum creatinine

Figure

  • Fig. 1 AUCs of blood biomarkers at ICU admission to predict postoperative MAKE or AKI. Missing values: plasma NGAL (MAKE: N=1/9, no MAKE: N=2/91; AKI: N=2/9, no AKI: N=0/91), hepcidin-25 (MAKE: N=0/9, no MAKE: N=1/91; AKI: N=0/9, no AKI: N=1/91), plasma NGAL:hepcidin-25 (MAKE: N=1/9, no MAKE: N=2/91; AKI: N=2/9, no AKI: N=1/91). *Indicates biomarker with inverse relationship to endpoints. Abbreviations: AKI, acute kidney injury; AUC, area under the ROC curve; BNP, B-type natriuretic peptide; CK, creatine kinase; CKMB, creatine kinase myocardial band; CRP, C-reactive protein; ICU, intensive care unit; IL, interleukin; MAKE, major adverse kidney events; NGAL, neutrophil gelatinase-associated lipocalin.


Cited by  2 articles

Hepcidin-25 as a Novel Kidney Biomarker for Cardiac Surgery-Associated Acute Kidney Injury
Sun Young Cho, Mina Hur
Ann Lab Med. 2021;41(4):355-356.    doi: 10.3343/alm.2021.41.4.355.

Neutrophil Gelatinase-Associated Lipocalin Cutoff Value Selection and Acute Kidney Injury Classification System Determine Phenotype Allocation and Associated Outcomes
Annemarie Albert, Sebastian Radtke, Louisa Blume, Rinaldo Bellomo, Michael Haase, Philipp Stieger, Ulrich Paul Hinkel, Rüdiger C. Braun-Dullaeus, Christian Albert
Ann Lab Med. 2023;43(6):539-553.    doi: 10.3343/alm.2023.43.6.539.


Reference

1. Thiele RH, Isbell JM, Rosner MH. 2015; AKI associated with cardiac surgery. Clin J Am Soc Nephrol. 10:500–14. DOI: 10.2215/CJN.07830814. PMID: 25376763. PMCID: PMC4348689.
Article
2. Kellum JA, Lameire N, Aspelin P, Barsoum RS, Burdmann EA, Goldstein SL, et al. 2012; Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for Acute Kidney Injury. Kidney Int Suppl. 2:1–138.
3. Thakar CV, Arrigain S, Worley S, Yared JP, Paganini EP. 2005; A clinical score to predict acute renal failure after cardiac surgery. J Am Soc Nephrol. 16:162–8. DOI: 10.1681/ASN.2004040331. PMID: 15563569.
Article
4. McCullough PA, Shaw AD, Haase M, Bouchard J, Waikar SS, Siew ED, et al. 2013; Diagnosis of acute kidney injury using functional and injury biomarkers: workgroup statements from the tenth Acute Dialysis Quality Initiative Consensus Conference. Contrib Nephrol. 182:13–29. DOI: 10.1159/000349963. PMID: 23689653.
Article
5. Haase M, Bellomo R, Haase-Fielitz A. 2010; Novel biomarkers, oxidative stress, and the role of labile iron toxicity in cardiopulmonary bypass-associated acute kidney injury. J Am Coll Cardiol. 55:2024–33. DOI: 10.1016/j.jacc.2009.12.046. PMID: 20447525.
Article
6. Leaf DE, Rajapurkar M, Lele SS, Mukhopadhyay B, Boerger EAS, Mc Causland FR, et al. 2019; Iron, hepcidin, and death in human AKI. J Am Soc Nephrol. 30:493–504. DOI: 10.1681/ASN.2018100979. PMID: 30737269. PMCID: PMC6405140.
Article
7. Balla G, Jacob HS, Balla J, Rosenberg M, Nath K, Apple F, et al. 1992; Ferritin: a cytoprotective antioxidant strategem of endothelium. J Biol Chem. 267:18148–53. DOI: 10.1016/S0021-9258(19)37165-0.
Article
8. Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, Yang J, et al. 2005; Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest. 115:610–21. DOI: 10.1172/JCI23056. PMID: 15711640. PMCID: PMC548316.
Article
9. Gueret G, Lion F, Guriec N, Arvieux J, Dovergne A, Guennegan C, et al. 2009; Acute renal dysfunction after cardiac surgery with cardiopulmonary bypass is associated with plasmatic IL6 increase. Cytokine. 45:92–8. DOI: 10.1016/j.cyto.2008.11.001. PMID: 19128984.
Article
10. Hur M, Kim H, Lee S, Cristofano F, Magrini L, Marino R, et al. 2014; Diagnostic and prognostic utilities of multimarkers approach using procalcitonin, B-type natriuretic peptide, and neutrophil gelatinase-associated lipocalin in critically ill patients with suspected sepsis. BMC Infect Dis. 14:224. DOI: 10.1186/1471-2334-14-224. PMID: 24761764. PMCID: PMC4006080.
Article
11. O'Neal JB, Shaw AD, Billings FT. 2016; Acute kidney injury following cardiac surgery: current understanding and future directions. Crit Care. 20:187. DOI: 10.1186/s13054-016-1352-z. PMID: 27373799. PMCID: PMC4931708.
12. Hajjar LA, Almeida JP, Fukushima JT, Rhodes A, Vincent J-L, Osawa EA, et al. 2013; High lactate levels are predictors of major complications after cardiac surgery. J Thorac Cardiovasc Surg. 146:455–60. DOI: 10.1016/j.jtcvs.2013.02.003. PMID: 23507124.
Article
13. Albert C, Zapf A, Haase M, Röver C, Pickering JW, Albert A, et al. 2020; 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. 76:826–41. DOI: 10.1053/j.ajkd.2020.05.015. PMID: 32679151.
Article
14. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. 2014; The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Int J Surg. 12:1495–9. DOI: 10.1016/j.ijsu.2014.07.013. PMID: 25046131.
Article
15. Haase M, Haase-Fielitz A, Plass M, Kuppe H, Hetzer R, Hannon C, et al. 2013; Prophylactic perioperative sodium bicarbonate to prevent acute kidney injury following open heart surgery: A multicenter double-blinded randomized controlled trial. PLoS Med. 10:e1001426. DOI: 10.1371/journal.pmed.1001426. PMID: 23610561. PMCID: PMC3627643.
Article
16. Albert C, Haase M, Albert A, Kropf S, Bellomo R, Westphal S, et al. 2020; Urinary biomarkers may complement the Cleveland score for prediction of adverse kidney events after cardiac surgery: A pilot study. Ann Lab Med. 40:131–41. DOI: 10.3343/alm.2020.40.2.131. PMID: 31650729. PMCID: PMC6822001.
Article
17. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute Dialysis Quality Initiative workgroup. 2004; Acute renal failure-definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 8:R204–12.
18. Englberger L, Suri RM, Li Z, Casey ET, Daly RC, Dearani JA, et al. 2011; Clinical accuracy of RIFLE and Acute Kidney Injury Network (AKIN) criteria for acute kidney injury in patients undergoing cardiac surgery. Crit Care. 15:R16. DOI: 10.1186/cc9960. PMID: 21232094. PMCID: PMC3222049.
Article
19. Park CM, Kim JS, Moon HW, Park S, Kim H, Ji M, et al. 2015; Usefulness of plasma neutrophil gelatinase-associated lipocalin as an early marker of acute kidney injury after cardiopulmonary bypass in Korean cardiac patients: a prospective observational study. Clin Biochem. 48:44–9. DOI: 10.1016/j.clinbiochem.2014.09.019. PMID: 25284002.
Article
20. Tuladhar SM, Püntmann VO, Soni M, Punjabi PP, Bogle RG. 2009; Rapid detection of acute kidney injury by plasma and urinary neutrophil gelatinase-associated lipocalin after cardiopulmonary bypass. J Cardiovasc Pharmacol. 53:261–6. DOI: 10.1097/FJC.0b013e31819d6139. PMID: 19247188.
Article
21. Kerr KF, Meisner A, Thiessen-Philbrook H, Coca SG, Parikh CR. 2014; Developing risk prediction models for kidney injury and assessing incremental value for novel biomarkers. Clin J Am Soc Nephrol. 9:1488–96. DOI: 10.2215/CJN.10351013. PMID: 24855282. PMCID: PMC4123400.
Article
22. Mandrekar JN. 2010; Receiver operating characteristic curve in diagnostic test assessment. J Thorac Oncol. 5:1315–6. DOI: 10.1097/JTO.0b013e3181ec173d. PMID: 20736804.
Article
23. Hanley JA, McNeil BJ. 1983; A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology. 148:839–43. DOI: 10.1148/radiology.148.3.6878708. PMID: 6878708.
Article
24. Pencina MJ, D'Agostino RB Sr, Steyerberg EW. 2011; Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med. 30:11–21. DOI: 10.1002/sim.4085. PMID: 21204120. PMCID: PMC3341973.
Article
25. Vanmassenhove J, Vanholder R, Nagler E, Van Biesen W. 2013; Urinary and serum biomarkers for the diagnosis of acute kidney injury: an in-depth review of the literature. Nephrol Dial Transplant. 28:254–73. DOI: 10.1093/ndt/gfs380. PMID: 23115326.
Article
26. Donadio C. 2014; Effect of glomerular filtration rate impairment on diagnostic performance of neutrophil gelatinase-associated lipocalin and B-type natriuretic peptide as markers of acute cardiac and renal failure in chronic kidney disease patients. Crit Care. 18:R39. DOI: 10.1186/cc13752. PMID: 24581340. PMCID: PMC4057335.
Article
27. Kim H, Hur M, Lee S, Marino R, Magrini L, Cardelli P, et al. 2017; Proenkephalin, neutrophil gelatinase-associated lipocalin, and estimated glomerular filtration rates in patients with sepsis. Ann Lab Med. 37:388–97. DOI: 10.3343/alm.2017.37.5.388. PMID: 28643487. PMCID: PMC5500737.
Article
28. Mikłaszewska M, Korohoda P, Zachwieja K, Mroczek T, Drożdż D, Sztefko K, et al. 2013; Serum interleukin 6 levels as an early marker of acute kidney injury on children after cardiac surgery. Adv Clin Exp Med. 22:377–86.
29. Choi N, Rigatto C, Zappitelli M, Gao A, Christie S, Hiebert B, et al. 2018; Urinary hepcidin-25 is elevated in patients that avoid acute kidney injury following cardiac surgery. Can J Kidney Health Dis. 5:2054358117744220. DOI: 10.1177/2054358117744224. PMID: 29399365. PMCID: PMC5788097.
Article
30. Yi A, Lee CH, Yun YM, Kim H, Moon HW, Hur M. 2021; Effectiveness of plasma and urine neutrophil gelatinase-associated lipocalin for predicting acute kidney injury in high-risk patients. Ann Lab Med. 41:60–7. DOI: 10.3343/alm.2021.41.1.60. PMID: 32829580. PMCID: PMC7443531.
Article
31. Prowle JR, Ostland V, Calzavacca P, Licari E, Ligabo EV, Echeverri JE, et al. 2012; Greater increase in urinary hepcidin predicts protection from acute kidney injury after cardiopulmonary bypass. Nephrol Dial Transplant. 27:595–602. DOI: 10.1093/ndt/gfr387. PMID: 21804084.
Article
32. Choi N, Whitlock R, Klassen J, Zappitelli M, Arora RC, Rigatto C, et al. 2019; Early intraoperative iron-binding proteins are associated with acute kidney injury after cardiac surgery. J Thorac Cardiovasc Surg. 157:287–97. DOI: 10.1016/j.jtcvs.2018.06.091. PMID: 30195593.
Article
33. van Swelm RPL, Wetzels JFM, Verweij VGM, Laarakkers CMM, Pertijs JCLM, van der Wijst J, et al. 2016; Renal handling of circulating and renal-synthesized hepcidin and its protective effects against hemoglobin-mediated kidney injury. J Am Soc Nephrol. 27:2720–32. DOI: 10.1681/ASN.2015040461. PMID: 26825531. PMCID: PMC5004644.
Article
34. Swaminathan S. 2018; Iron homeostasis pathways as therapeutic targets in acute kidney injury. Nephron. 140:156–9. DOI: 10.1159/000490808. PMID: 29982259. PMCID: PMC6165684.
Article
35. Mårtensson J, Glassford NJ, Jones S, Eastwood GM, Young H, Peck L, et al. 2015; Urinary neutrophil gelatinase-associated lipocalin to hepcidin ratio as a biomarker of acute kidney injury in intensive care unit patients. Minerva Anestesiol. 81:1192–200.
36. Ostermann M, Bellomo R, Burdmann EA, Doi K, Endre ZH, Goldstein SL, et al. 2020; Controversies in acute kidney injury: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference. Kidney Int. 98:294–309. DOI: 10.1016/j.kint.2020.04.020. PMID: 32709292.
37. Albert C, Haase M, Albert A, Zapf A, Braun-Dullaeus RC, Haase-Fielitz A. 2021; Biomarker-guided risk assessment for acute kidney injury: time for clinical implementation? Ann Lab Med. 41:1–15. DOI: 10.3343/alm.2021.41.1.1. PMID: 32829575. PMCID: PMC7443517.
Article
38. Haase-Fielitz A, Elitok S, Schostak M, Ernst M, Isermann B, Albert C, et al. 2020; The effects of intensive versus routine treatment in patients with acute kidney injury. Dtsch Arztebl Int. 117:289–96. DOI: 10.3238/arztebl.2020.0289. PMID: 32530412. PMCID: PMC7297063.
Article
39. Göcze I, Jauch D, Götz M, Kennedy P, Jung B, Zeman F, et al. 2018; Biomarker-guided intervention to prevent acute kidney injury after major surgery: the prospective randomized BigpAK study. Ann Surg. 267:1013–20. DOI: 10.1097/SLA.0000000000002485. PMID: 28857811.
40. Meersch M, Schmidt C, Hoffmeier A, Van Aken H, Wempe C, Gerss J, et al. 2017; 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. 43:1551–61. DOI: 10.1007/s00134-016-4670-3. PMID: 28110412. PMCID: PMC5633630.
Article
Full Text Links
  • ALM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr