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Licensed Unlicensed Requires Authentication Published by De Gruyter November 16, 2013

NGAL, L-FABP, and KIM-1 in comparison to established markers of renal dysfunction

  • Leon Holzscheiter EMAIL logo , Claus Beck , Sandra Rutz , Ekaterina Manuilova , Ingrid Domke , Walter G. Guder and Walter Hofmann

Abstract

Background: New urinary biomarkers like neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid binding protein (L-FABP), and kidney injury molecule-1 (KIM-1) open the opportunity to detect kidney injuries in early stages. Our study aimed at evaluating NGAL, L-FABP, and KIM-1 in comparison to established markers of urine protein differentiation for detection of renal dysfunction.

Methods: On the basis of the PROTIS expert system (for differentiation of glomerulo-/tubulopathy) urine and plasma samples of 263 randomly selected patients were routinely examined (urine: total protein, albumin, IgG, α1-microglobulin, creatinine, and dip stick results for leukocytes, blood, protein, glucose, pH, and nitrite; plasma: creatinine and cystatin C) followed by the analysis of the new urine biomarkers NGAL (CMIA), L-FABP (ECLIA), and KIM-1 (ELISA).

Results: Of the three new markers L-FABP showed the highest correlation with α1-microglobulin (r=0.76, p<0.01) and was closest associated with the degree of tubular proteinuria assessed by the PROTIS system. NGAL distinguished the PROTIS proteinuria groups with distinctive tubular proteinurias from the controls as well, but revealed a marked diagnostic influence by leukocyturia. Urinary KIM-1 revealed only a weak diagnostic value for the detection of renal injury.

Conclusions: Urinary NGAL and L-FABP proved to be promising candidates for detecting injuries of the renal tubular system over a broad range of clinical conditions. L-FABP showed a better diagnostic performance and a lower interference by leukocyturia and hematuria than NGAL. Both markers may serve as sensitive tissue injury markers in addition to the established markers of renal functional impairment.


Corresponding author: Leon Holzscheiter, StKM – Klinische Chemie, Kölner Platz 1, Munich 80804, Germany, Phone: +49 8930682675, Fax: +49 8930682125, E-mail:

Acknowledgments

We thank Slavica Deiter for excellent technical assistance.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research funding played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Research funding: None declared.

Employment or leadership: Claus Beck, Ingrid Domke, Ekaterina Manuilova, and Sandra Rutz are employees of Roche Diagnostics. The other authors declared no competing interests.

Honorarium: None declared.

Footnote: COBAS E and ELECSYS are trademarks of Roche.

References

1. Noiri E, Doi K, Negishi K, Tanaka T, Hamasaki Y, Fujita T, et al. Urinary fatty acid-binding protein 1: an early predictive biomarker of kidney injury [review]. Am J Physiol Renal Physiol 2009;296:F669–79.10.1152/ajprenal.90513.2008Search in Google Scholar PubMed PubMed Central

2. Guder WG, Hofmann W. Clinical role of urinary low molecular weight proteins: their diagnostic and prognostic implications. Scand J Clin Lab Invest 2008;68:95–8.10.1080/00365510802150174Search in Google Scholar PubMed

3. Hofmann W, Ehrich JH, Guder WG, Keller F, Scherberich J. Diagnostic pathways for exclusion and diagnosis of kidney diseases. Clin Lab 2012;58:871–89.Search in Google Scholar

4. Bonventre JV, Venkata S, Himmelfarb J, Sayegh MH, editors. Chronic kidney disease, dialysis, and transplantation, 3rd ed. (Expert Consult Series): a companion to Brenner and Rector’s the kidney. Chapter 48. Acute kidney injury: biomarkers from bench to bedside. Philadelphia: Saunders, Elsevier Health Sciences, 2010.Search in Google Scholar

5. Nielsen BS, Borregaard N, Bundgaard JR, Timshel S, Sehested M, Kjeldsen L. Induction of NGAL synthesis in epithelial cells of human colorectal neoplasia and inflammatory bowel diseases. Gut 1996;38:414–20.10.1136/gut.38.3.414Search in Google Scholar PubMed PubMed Central

6. Kotyza J, Bunatova K, Pesek M, Puzman P. Pleural injury and pleurisy-induced progelatinase B/proMMP-9 is associated with markers of neutrophil degranulation. Scand J Clin Lab Invest 2006;66:487–96.10.1080/00365510600791716Search in Google Scholar PubMed

7. Anwaar I, Gottsater A, Ohlsson K, Mattiasson I, Lindgärde F. Increasing levels of leukocyte-derived inflammatory mediators in plasma and camp in platelets during follow-up after acute cerebral ischemia. Cerebrovasc Dis 1998;8:310–7.10.1159/000015873Search in Google Scholar PubMed

8. Clerico A, Galli C, Fortunato A, Ronco C. Neutrophil gelatinase-associated lipocalin (NGAL) as biomarker of acute kidney injury: a review of the laboratory characteristics and clinical evidences. Clin Chem Lab Med 2012;50:1505–17.10.1515/cclm-2011-0814Search in Google Scholar PubMed

9. Cruz DN, Goh CY, Palazzuoli A, Slavin L, Calabrò A, Ronco C, et al. Laboratory parameters of cardiac and kidney dysfunction in cardio-renal syndromes. Heart Fail Rev 2011;16:545–51.10.1007/s10741-011-9231-9Search in Google Scholar PubMed

10. Zhang Z, Humphreys BD, Bonventre JV. Shedding of the urinary biomarker kidney injury molecule-1 (KIM-1) is regulated by MAP kinases and juxtamembrane region. J Am Soc Nephrol 2007;18:2704–14.10.1681/ASN.2007030325Search in Google Scholar PubMed

11. Ichimura T, Bonventre JV, Bailly V, Wei H, Hession CA, Cate RL, et al. Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem 1998;273:4135–42.10.1074/jbc.273.7.4135Search in Google Scholar PubMed

12. Doi K, Negishi K, Ishizu T, Katagiri D, Fujita T, Matsubara T, et al. Evaluation of new acute kidney injury biomarkers in a mixed intensive care unit. Crit Care Med 2011;39:2464–9.10.1097/CCM.0b013e318225761aSearch in Google Scholar PubMed

13. Trof RJ, Di Maggio F, Leereis J, Groeneveld AB. Biomarkers of acute renal injury and renal failure. Shock 2006;26:245–53.10.1097/01.shk.0000225415.5969694.ceSearch in Google Scholar PubMed

14. Tsukasa N, Sugaya T, Node K, Ueda Y, Koide H. Urinary excretion of liver-type fatty acid-binding protein in contrast medium-induced nephropathy AJKD 2006;47:439–44.10.1053/j.ajkd.2005.11.006Search in Google Scholar PubMed

15. Portilla D, Dent C, Sugaya T, Nagothu KK, Kundi I, Moore P, et al. Liver fatty acid-binding protein as a biomarker of acute kidney injury after cardiac surgery. Kidney Int 2008;73:465–72.10.1038/sj.ki.5002721Search in Google Scholar PubMed

16. Han WK, Waikar SS, Johnson A, Betensky RA, Dent CL, Devarajan P, et al. Urinary biomarkers in the early diagnosis of acute kidney injury. Kidney Int 2008;73:863–9.10.1038/sj.ki.5002715Search in Google Scholar PubMed PubMed Central

17. Hofmann W, Ruth D, Guder WG. Urine protein differentiation and Protis, a new expert system for its interpretation. Riv Med Lab JLM 2003;4:67–8.Search in Google Scholar

18. Hofmann W, Sedlmeir-Hofmann C, Ivandić M, Ruth D, Luppa P. PROTIS: use of combined biomarkers for providing diagnostic information on disease states. Methods Mol Biol 2010;641: 123–42.10.1007/978-1-60761-711-2_8Search in Google Scholar PubMed

19. Chaturvedi S, Farmer T, Kapke GF. Assay validation for KIM-1: human urinary renal dysfunction biomarker. Int J Biol Sci 2009;5:128–34.10.7150/ijbs.5.128Search in Google Scholar PubMed PubMed Central

20. Nickolas TL, O’Rourke MJ, Yang J, Sise ME, Canetta PA, Barasch N, et al. Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Ann Intern Med 2008;148:810–9.10.7326/0003-4819-148-11-200806030-00003Search in Google Scholar PubMed PubMed Central

21. Bolignano D, Donato V, Coppolino G, Campo S, Buemi A, Lacquaniti A, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. Am J Kidney Dis 2008;52:595–605.10.1053/j.ajkd.2008.01.020Search in Google Scholar PubMed

22. Barresi V, Ieni A, Bolignano D, Magno C, Buemi M, Barresi G. Neutrophil gelatinase-associated lipocalin immunoexpression in renal tumors: correlation with histotype and histological grade. Oncol Rep 2010;24:305–10.10.3892/or_00000860Search in Google Scholar PubMed

23. Mishra J, Mori K, Ma Q, Kelly C, Barasch J, Devarajan P. Neutrophil gelatinase-associated lipocalin: a novel early urinary biomarker for cisplatin nephrotoxicity. Am J Nephrol 2004;24:307–15.10.1159/000078452Search in Google Scholar PubMed

24. Decavele AS, Dhondt L, De Buyzere ML, Delanghe JR. Increased urinary neutrophil gelatinase associated lipocalin in urinary tract infections and leukocyturia. Clin Chem Lab Med 2011;49:999–1003.10.1515/CCLM.2011.156Search in Google Scholar

25. Bolignano D, Coppolino G, Donato V, Lacquaniti A, Bono C, Buemi M. Neutrophil gelatinase-associated lipocalin (NGAL): a new piece of the anemia puzzle? Med Sci Monit 2010;16:RA131–5.Search in Google Scholar

26. Bolignano D, Coppolino G, Aloisi C, Romeo A, Nicocia G, Buemi M. Effect of a single intravenous immunoglobulin infusion on neutrophil gelatinase-associated lipocalin levels in proteinuric patients with normal renal function. J Investig Med 2008;56:997–1003.10.2310/JIM.0b013e31818e7e95Search in Google Scholar

27. Bolignano D, Della Torre A, Lacquaniti A, Costantino G, Fries W, Buemi M. Neutrophil gelatinase-associated lipocalin levels in patients with Crohn disease undergoing treatment with infliximab. J Investig Med 2010;58:569–71.10.2310/JIM.0b013e3181ccc20cSearch in Google Scholar

28. Lippi G, Plebani M. Neutrophil gelatinase-associated lipocalin (NGAL): the laboratory perspective. Clin Chem Lab Med 2012;50:1483–7.10.1515/cclm-2012-0344Search in Google Scholar

29. Devarajan P. Emerging urinary biomarkers in the diagnosis of acute kidney injury. Expert Opin Med Diagn 2008;2:387–98.10.1517/17530059.2.4.387Search in Google Scholar

30. Kamijo A, Sugaya T, Hikawa A, Okada M, Okumura F, Yamanouchi M, et al. Urinary excretion of fatty acid-binding protein reflects stress overload on the proximal tubules. Am J Pathol 2004;165:1243–55.10.1016/S0002-9440(10)63384-6Search in Google Scholar

31. Bonventre JV. Kidney injury molecule-1 (KIM-1): a urinary biomarker and much more. Nephrol Dial Transpl 2009;24:3265–8.10.1093/ndt/gfp010Search in Google Scholar PubMed

32. Han WK, Alinani A, Wu CL, Michaelson D, Loda M, McGovern FJ, et al. Human kidney injury molecule-1 is a tissue and urinary tumor marker of renal cell carcinoma. J Am Soc Nephrol 2005;16:1126–34.10.1681/ASN.2004070530Search in Google Scholar PubMed PubMed Central

33. Nickolas TL, Schmidt-Ott KM, Canetta P, Forster C, Singer E, Sise M, et al. Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: a multicenter prospective cohort study. J Am Coll Cardiol 2012;59:246–55.10.1016/j.jacc.2011.10.854Search in Google Scholar PubMed PubMed Central

Received: 2013-8-26
Accepted: 2013-10-13
Published Online: 2013-11-16
Published in Print: 2014-04-01

©2014 by Walter de Gruyter Berlin/Boston

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