Startseite Urinary orosomucoid: a novel, early biomarker of sepsis with promising diagnostic performance
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Urinary orosomucoid: a novel, early biomarker of sepsis with promising diagnostic performance

  • Péter Kustán EMAIL logo , Balázs Szirmay , Zoltán Horváth-Szalai , Andrea Ludány , Gábor L. Kovács , Attila Miseta , Tamás Kőszegi und Diána Mühl
Veröffentlicht/Copyright: 7. November 2016
Veröffentlichen auch Sie bei De Gruyter Brill

Abstract

Background:

In order to help clinical decision making, we investigated the diagnostic and prognostic ability of urinary orosomucoid (u-ORM) as a new sepsis biomarker, and compared its performance to classical inflammatory parameters.

Methods:

We monitored u-ORM in septic (n=43) and SIRS (n=13) patients in a 5-day follow-up study vs. control patients (n=30). U-ORM was measured by a newly developed turbidimetric assay. U-ORM values were referred to urinary creatinine and expressed as u-ORM/u-CREAT (mg/mmol).

Results:

Significantly higher (p<0.001) u-ORM/u-CREAT levels were found in sepsis than in SIRS. Both intensive care unit (ICU) groups showed strongly elevated values compared to controls (p<0.001). The medians of admission u-ORM/u-CREAT levels were 19.2 in sepsis, 2.1 in SIRS and 0.2 mg/mmol in controls. The area under the receiver operating characteristic curve for distinguishing SIRS from sepsis was found to be 0.954 for u-ORM/u-CREAT, superior to serum ORM and hsCRP. U-ORM levels did not change during the 5-day follow-up and were independent of the severity of sepsis however, we found extremely elevated u-ORM/u-CREAT values in dialyzed septic patients (52.2 mg/mmol as median).

Conclusions:

The early and relevant increase of u-ORM in sepsis suggests that it might be a promising novel marker of sepsis and could be a valuable part of routine laboratory and clinical practice.


Corresponding author: Dr. Péter Kustán, Department of Laboratory Medicine, University of Pécs Medical School, 7624 Pécs, Ifjúság u. 13, Hungary, Phone: +36 30 248 3289, Fax: +36 72 536 121

Acknowledgments

The present scientific contribution is dedicated to the 650th anniversary of the foundation of the University of Pécs, Hungary. Hereby we express our special thanks for the invaluable help of our nurses and colleagues. We are grateful for Dako A/S Company for providing us the ORM reagents and for Roche Magyarország Kft for the opportunity and technical support of using a developmental channel in our measurements.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: The work was supported by GINOP-2.3.2-15-2016-00021 and NKFI-EPR K/115394/2015 grants.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) 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.

References

1. Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med 2013;369:840–51.10.1056/NEJMra1208623Suche in Google Scholar

2. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001;29:1303–10.10.1097/00003246-200107000-00002Suche in Google Scholar

3. Levy MM, Artigas A, Phillips GS, Rhodes A, Beale R, Osborn T, et al. Outcomes of the Surviving Sepsis Campaign in intensive care units in the USA and Europe: a prospective cohort study. Lancet Infect Dis 2012;12:919–24.10.1016/S1473-3099(12)70239-6Suche in Google Scholar

4. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013;39:165–228.10.1007/s00134-012-2769-8Suche in Google Scholar

5. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368–77.10.1056/NEJMoa010307Suche in Google Scholar

6. Pierrakos C, Vincent JL. Sepsis biomarkers: a review. Crit Care 2010;14:R15.10.1186/cc8872Suche in Google Scholar

7. Waller KV, Ward KM, Mahan JD, Wismatt DK. Current concepts in proteinuria. Clin Chem 1989;35:755–65.10.1093/clinchem/35.5.755Suche in Google Scholar

8. Alge JL, Arthur JM. Biomarkers of AKI: a review of mechanistic relevance and potential therapeutic implications. Clin J Am Soc Nephrol 2015;10:147–55.10.2215/CJN.12191213Suche in Google Scholar

9. Schmid K. α1-acid glycoprotein. In: Putnam FW, editor. The Plasma Proteins. New York: Academic Press, 1975:183–228.10.1016/B978-0-12-568401-9.50011-6Suche in Google Scholar

10. Hochepied T, Berger FG, Baumann H, Libert C. Alpha(1)-acid glycoprotein: an acute phase protein with inflammatory and immunomodulating properties. Cytokine Growth Factor Rev 2003;14:25–34.10.1016/S1359-6101(02)00054-0Suche in Google Scholar

11. Haraldsson BS, Johnsson EK, Rippe B. Glomerular permselectivity is dependent on adequate serum concentrations of orosomucoid. Kidney Int 1992;41:310–6.10.1038/ki.1992.43Suche in Google Scholar

12. Hjalmarsson C, Lidell ME, Haraldsson B. Beneficial effects of orosomucoid on the glomerular barrier in puromycin aminonucleoside-induced nephrosis. Nephrol Dial Transplant 2006;21:1223–30.10.1093/ndt/gfk050Suche in Google Scholar

13. Hochepied T, Van Molle W, Berger FG, Baumann H, Libert C. Involvement of the acute phase protein alpha 1-acid glycoprotein in nonspecific resistance to a lethal Gram-negative infection. J Biol Chem 2000;275:14903–9.10.1074/jbc.275.20.14903Suche in Google Scholar

14. Moore DF, Rosenfeld MR, Gribbon PM, Winlove CP, Tsai CM. Alpha-1-acid (AAG, orosomucoid) glycoprotein: interaction with bacterial lipopolysaccharide and protection from sepsis. Inflammation 1997;21:69–82.10.1023/A:1027342909423Suche in Google Scholar

15. Muchitsch EM, Auer W, Pichler L. Effects of alpha 1-acid glycoprotein in different rodent models of shock. Fundam Clin Pharmacol 1998;12:173–81.10.1111/j.1472-8206.1998.tb00938.xSuche in Google Scholar

16. Fournier T, Medjoubi NN, Porquet D. Alpha-1-acid glycoprotein. Biochim Biophys Acta 2000;1482:157–71.10.1016/S0167-4838(00)00153-9Suche in Google Scholar

17. Ceciliani F, Pocacqua V. The acute phase protein alpha1-acid glycoprotein: a model for altered glycosylation during diseases. Curr Protein Pept Sci 2007;8:91–108.10.2174/138920307779941497Suche in Google Scholar PubMed

18. Xiao K, Su L, Yan P, Han B, Li J, Wang H, et al. Alpha-1-acid glycoprotein as a biomarker for the early diagnosis and monitoring the prognosis of sepsis. J Crit Care 2015;30:744–51.10.1016/j.jcrc.2015.04.007Suche in Google Scholar PubMed

19. Hou LN, Li F, Zeng QC, Su L, Chen PA, Xu ZH, et al. Excretion of urinary orosomucoid 1 protein is elevated in patients with chronic heart failure. PLoS One 2014;9:e107550.10.1371/journal.pone.0107550Suche in Google Scholar PubMed PubMed Central

20. Jiang H, Guan G, Zhang R, Liu G, Liu H, Hou X, et al. Increased urinary excretion of orosomucoid is a risk predictor of diabetic nephropathy. Nephrology (Carlton) 2009;14:332–7.10.1111/j.1440-1797.2008.01053.xSuche in Google Scholar PubMed

21. Christiansen MS, Hommel E, Friberg L, Molvig J, Magid E, Feldt-Rasmussen B. Increased urinary orosomucoid excretion is not related to impaired renal function in patients with type 2 diabetes. J Diabetes Complications 2010;24:28–36.10.1016/j.jdiacomp.2008.08.001Suche in Google Scholar PubMed

22. Christiansen MS, Hommel E, Magid E, Feldt-Rasmussen B. Orosomucoid in urine is a powerful predictor of cardiovascular mortality in normoalbuminuric patients with type 2 diabetes at five years of follow-up. Diabetologia 2005;48:386–93.10.1007/s00125-004-1630-1Suche in Google Scholar PubMed

23. Christiansen MS, Iversen K, Larsen CT, Goetze JP, Hommel E, Molvig J, et al. Increased urinary orosomucoid excretion: a proposed marker for inflammation and endothelial dysfunction in patients with type 2 diabetes. Scand J Clin Lab Invest 2009;69:272–81.10.1080/00365510802531100Suche in Google Scholar PubMed

24. Christiansen MS, Hesse D, Ekbom P, Hesse U, Damm P, Hommel E, et al. Increased urinary orosomucoid excretion predicts preeclampsia in pregnant women with pregestational type 1 diabetes. Diabetes Res Clin Pract 2010;89:16–21.10.1016/j.diabres.2010.03.018Suche in Google Scholar PubMed

25. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med 2003;29:530–8.10.1007/s00134-003-1662-xSuche in Google Scholar PubMed

26. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2012;2:1–138.Suche in Google Scholar

27. Zappitelli M, Greenberg JH, Coca SG, Krawczeski CD, Li S, Thiessen-Philbrook HR, et al. Association of definition of acute kidney injury by cystatin C rise with biomarkers and clinical outcomes in children undergoing cardiac surgery. J Am Med Assoc Pediatr 2015;169:583–91.10.1001/jamapediatrics.2015.54Suche in Google Scholar PubMed PubMed Central

28. Zhou J, Liu Y, Tang Y, Liu F, Zhang L, Zeng X, et al. A comparison of RIFLE, AKIN, KDIGO, and Cys-C criteria for the definition of acute kidney injury in critically ill patients. Int Urol Nephrol 2016;48:125–32.10.1007/s11255-015-1150-6Suche in Google Scholar PubMed

29. Christiansen MS, Blirup-Jensen S, Foged L, Larsen M, Magid E. A particle-enhanced turbidimetric immunoassay for quantitative determination of orosomucoid in urine: development, validation and reference values. Clin Chem Lab Med 2004;42:1168–77.10.1515/CCLM.2004.237Suche in Google Scholar PubMed

30. Kustán P, Szirmay B, Mühl D, Ludány A. Human orosomucoid in the clinical laboratory. In: Kőszegi T, editor. Techniques with Applicability in Medical Practice. Saarbrücken: LAP Lambert Academic Publishing, 2015:101–20.Suche in Google Scholar

31. Magid E, Guldager H, Hesse D, Christiansen MS. Monitoring urinary orosomucoid in acute inflammation: observations on urinary excretion of orosomucoid, albumin, alpha1-microglobulin, and IgG. Clin Chem 2005;51:2052–8.10.1373/clinchem.2005.055442Suche in Google Scholar PubMed

32. Di Somma S, Magrini L, Travaglino F, Lalle I, Fiotti N, Cervellin G, et al. Opinion paper on innovative approach of biomarkers for infectious diseases and sepsis management in the emergency department. Clin Chem Lab Med 2013;51:1167–75.10.1515/cclm-2012-0795Suche in Google Scholar PubMed

33. Becze Z, Molnar Z, Fazakas J. Can procalcitonin levels indicate the need for adjunctive therapies in sepsis? Int J Antimicrob Agents 2015;46(Suppl 1):S13–8.10.1016/j.ijantimicag.2015.11.002Suche in Google Scholar

34. Laszlo I, Trasy D, Molnar Z, Fazakas J. Sepsis: From Pathophysiology to Individualized Patient Care. J Immunol Res 2015;2015:510436.10.1155/2015/510436Suche in Google Scholar

35. Logdberg L, Wester L. Immunocalins: a lipocalin subfamily that modulates immune and inflammatory responses. Biochim Biophys Acta 2000;1482:284–97.10.1016/S0167-4838(00)00164-3Suche in Google Scholar

36. Suzuki M, Wiers K, Brooks EB, Greis KD, Haines K, Klein-Gitelman MS, et al. Initial validation of a novel protein biomarker panel for active pediatric lupus nephritis. Pediatr Res 2009;65:530–6.10.1203/PDR.0b013e31819e4305Suche in Google Scholar

37. Kőszegi T, Kustán P, Ludány A, Györgyi E, Woth G, Mühl D, et al. Urinary orosomucoid in sepsis. Clin Chem Lab Med 2012;50:eA33.Suche in Google Scholar

38. Barroso-Sousa R, Lobo RR, Mendonca PR, Memoria RR, Spiller F, Cunha FQ, et al. Decreased levels of alpha-1-acid glycoprotein are related to the mortality of septic patients in the emergency department. Clinics 2013;68:1134–9.10.6061/clinics/2013(08)12Suche in Google Scholar

39. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). J Am Med Assoc 2016;315:801–10.10.1001/jama.2016.0287Suche in Google Scholar PubMed PubMed Central

Received: 2016-9-19
Accepted: 2016-9-29
Published Online: 2016-11-7
Published in Print: 2017-2-1

©2017 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Commutable samples with assigned target concentrations may help us harmonise general chemistry results
  4. Reviews
  5. Performance of point-of-care HbA1c test devices: implications for use in clinical practice – a systematic review and meta-analysis
  6. Cardiac troponins and mortality in type 1 and 2 myocardial infarction
  7. Opinion Paper
  8. Criteria for assigning laboratory measurands to models for analytical performance specifications defined in the 1st EFLM Strategic Conference
  9. Genetics and Molecular Diagnostics
  10. External quality assessment for human papillomavirus 16/18 DNA detection and genotyping in Shanghai, China
  11. General Clinical Chemistry and Laboratory Medicine
  12. Analytical performance of 17 general chemistry analytes across countries and across manufacturers in the INPUtS project of EQA organizers in Italy, the Netherlands, Portugal, United Kingdom and Spain
  13. Commutability of proficiency testing material containing tobramycin: a study within the framework of the Dutch Calibration 2.000 project
  14. Optimization and validation of moving average quality control procedures using bias detection curves and moving average validation charts
  15. Extending laboratory automation to the wards: effect of an innovative pneumatic tube system on diagnostic samples and transport time
  16. Smart management of sample dilution using an artificial neural network to achieve streamlined processes and saving resources: the automated nephelometric testing of serum free light chain as case study
  17. An integrated proteomic and peptidomic assessment of the normal human urinome
  18. An alternative inhibition method for determining cross-reactive allergens
  19. Validation of a new assay for α-synuclein detection in cerebrospinal fluid
  20. Reference Values and Biological Variations
  21. Intra-individual variation of plasma trimethylamine-N-oxide (TMAO), betaine and choline over 1 year
  22. Cancer Diagnostics
  23. Predictive performance of TPA testing for recurrent disease during follow-up after curative intent surgery for colorectal carcinoma
  24. Cardiovascular Diseases
  25. Mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-atrial natriuretic peptide (MR-proANP) in severe aortic valve stenosis: association with outcome after transcatheter aortic valve implantation (TAVI)
  26. Association between apolipoprotein E polymorphisms and premature coronary artery disease: a meta-analysis
  27. Urinary orosomucoid: a novel, early biomarker of sepsis with promising diagnostic performance
  28. Letters to the Editor
  29. CT or MRI
  30. Reply to: CT or MRI in the diagnosis of right lower quadrant abdominal pain?
  31. Quantification of daratumumab in the serum protein electrophoresis
  32. Response to: Interference of daratumumab on the serum protein electrophoresis
  33. Glycated albumin: correlation to HbA1c and preliminary reference interval evaluation
  34. Using “big data” to describe the effect of seasonal variation in thyroid-stimulating hormone
  35. IgE multiple myeloma: a new case report
  36. Therapeutic decision-making process in the intensive care unit: role of biological point-of-care testing
  37. How can we evaluate differences between serial measurements on the same sample? A new approach based on within-subject biological variation
Heruntergeladen am 18.11.2025 von https://www.degruyterbrill.com/document/doi/10.1515/cclm-2016-0840/html?lang=de
Button zum nach oben scrollen