Home Biological variation and prognosis usefulness of new biomarkers in liver transplantation
Article
Licensed
Unlicensed Requires Authentication

Biological variation and prognosis usefulness of new biomarkers in liver transplantation

  • Diego Miguel , Belén Prieto EMAIL logo and Francisco V. Álvarez
Published/Copyright: December 8, 2012

Abstract

Background: An observational retrospective study has been conducted, including 52 patients (37 male and 15 female), ranging from 22 to 65 years old, who underwent an orthotopic liver transplantation (OLT) at the Hospital Universitario Central de Asturias (HUCA) between 2007 and 2010.

Methods: The main objective was to evaluate the post-OLT critical complication prognosis usefulness of the precursors of three new biomarkers: mid-regional proadrenomedullin (MR-proADM), carboxy-terminal-proendothelin-1 (CT-ProET-1) and mid-regional proatrial natriuretic peptide (MR-ProANP). As all of them are blood pressure mediators, stress-associated physiological phenomena are expected to affect their expression and secretion, mainly those related to blood circulation. Therefore, as a second goal, the biological variability of the biomarkers has been studied in a set of OLT patients without complications during the first postoperative week. The knowledge of the reference change value of the new biomarkers will be interesting for their correct interpretation in future investigations. The prognostic value of the new biomarkers was also compared to that of procalcitonin (PCT).

Results: It has been shown that the basal concentration of the biomarkers is higher in patients that undergo OLT than in the normal population, correlating with the severity of the pathology. The intra-individual biological variation of these biomarkers is similar to other biochemical parameters, the reference change value for OLT patients being 90% for CT-proET-1, 112% for MR-proADM and 127% for MR-proANP.

Conclusions: Multivariate analysis showed that MR-proADM was the best biomarker for the prognosis of severe complications.


Corresponding author: Belén Prieto, PhD, Clinical Biochemistry, Laboratory of Medicine, Hospital Universitario Central de Asturias, c/Celestino Villamil, s/n, 33006 Oviedo, Spain, Phone/Fax: +34 985108073

Reagents needed for the new biomarkers analysis have been supplied by BRAHMS, Thermo Fisher Scientific.

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.

Supply of the reagents 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: None declared.

Honorarium: None declared.

References

1. Matesanz R, de la Rosa G. Liver transplantation: the Spanish experience. Digest Liver Dis Suppl 2009;3:75–81.10.1016/S1594-5804(09)60030-9Search in Google Scholar

2. Russ PD, Elliot DE, Durham JD, Garg K, Wasch ME, Kam I. Liver transplantation complications. Available from: http://emedicine.com/radio/topic883.htm#section. 2007.Search in Google Scholar

3. Hickman PE, Potter JM, Pesce AJ. Clinical chemistry and post-liver-transplant monitoring. Clin Chem 1997;43: 1546–54.10.1093/clinchem/43.8.1546Search in Google Scholar PubMed

4. Kunz D, Pross M, Konig W, Lippert H, Manger T. Diagnostic relevance of procalcitonin, IL-6 and cellular immune status in the early phase after liver transplantation. Transplant Proc 1998;30:2398–9.10.1016/S0041-1345(98)00667-8Search in Google Scholar

5. Moreno R, Berenguer M. Post-liver transplantation medical complications. Ann Hepatol 2006;5:77–85.10.1016/S1665-2681(19)32022-8Search in Google Scholar PubMed

6. Warle MC, Metselaar HJ, Hop WC, Gyssens IC, Kap M, Kwekkeboom J, et al. Early differentiation between rejection and infection in liver transplant patients by serum and biliary cytokine patterns. Transplantation 2003;75:146–51.10.1097/00007890-200301150-00026Search in Google Scholar PubMed

7. Zhao X, Koshiba T, Fujimoto Y, Pirenne J, Yoshizawa A, Ito T, et al. Proinflammatory and antiinflammatory cytokine production during ischemia-reperfusion injury in a case of identical twin living donor liver transplantation using no immunosuppression. Transplant Proc 2005;37:392–4.10.1016/j.transproceed.2004.12.272Search in Google Scholar

8. Santiago F, Bueno P, Olmedo C, Comino A, Hassan L, Ferron-Celma I, et al. Time course of intraoperative cytokine levels in liver transplant recipients. Transplant Proc 2006;38:2492–4.10.1016/j.transproceed.2006.08.064Search in Google Scholar PubMed

9. Oberhoffer M, Vogelsang H, Jager L, Reinhart K. Katacalcin and calcitonin immunoreactivity in different types of leukocytes indicate intracellular procalcitonin content. J Crit Care 1999;14:29–33.10.1016/S0883-9441(99)90005-9Search in Google Scholar PubMed

10. Chieveley-Williams S, Hamilton-Davies C. The role of the gut in major surgical postoperative morbidity. Int Anesthesiol Clin 1999;37:81–110.10.1097/00004311-199903720-00006Search in Google Scholar

11. Hammer S, Meisner F, Hammer C, Seidel D. Use of procalcitonin as indicator of nonviral infections in transplantation and related immunologic diseases. Transplant Rev 2000;14:52–63.10.1016/S0955-470X(00)80010-5Search in Google Scholar

12. Kretzschmar M, Kruger A, Schirrmeister W. Procalcitonin following elective partial liver resection – origin from the liver? Acta Anaesthesiol Scand 2001;45:1162–7.10.1034/j.1399-6576.2001.450918.xSearch in Google Scholar PubMed

13. Matwiyoff GN, Prahl JD, Miller RJ, Carmichael JJ, Amundson DE, Seda G, et al. Immune regulation of procalcitonin: a biomarker and mediator of infection. Inflamm Res 2012;61:401–9.10.1007/s00011-012-0439-5http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000303103300001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar PubMed

14. Staehler M, Hammer C, Meiser B, Reichart B. Procalcitonin: a new marker for differential diagnosis of acute rejection and bacterial infection in heart transplantation. Transplant Proc 1997;29:584–5.10.1016/S0041-1345(96)00314-4Search in Google Scholar PubMed

15. Hammer S, Meisner F, Dirschedl P, Hobel G, Fraunberger P, Meiser B, et al. Procalcitonin: a new marker for diagnosis of acute rejection and bacterial infection in patients after heart and lung transplantation. Transpl Immunol 1998;6:235–41.10.1016/S0966-3274(98)80013-0Search in Google Scholar PubMed

16. Christ-Crain M, Morgenthaler NG, Struck J, Harbarth S, Bergmann A, Müller B. Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study. Crit Care 2005;9:816–24.10.1186/cc3885Search in Google Scholar PubMed PubMed Central

17. Miguel D, Prieto B, Costa M, Coto D, Álvarez FV. Cord blood plasma reference intervals for potential sepsis markers: pro-adrenomedullin, pro-endothelin and pro-atrial natriuretic peptide. Clin Biochem 2011;44:337–41.10.1016/j.clinbiochem.2010.12.012http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000287561600013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar PubMed

18. Fraser CG. Biological variation: from principles to practice. Washington DC: AACC Press, 2001.Search in Google Scholar

19. Prieto B, Llorente E, González-Pinto I, Álvarez FV. Plasma procalcitonin measured by time-resolved amplified cryptate emission (TRACE) in liver transplant patients. A prognosis marker of early infectious and non-infectious postoperative complications. Clin Chem Lab Med 2008;46:660–6.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000256534300011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar PubMed

20. Fábrega E, Crespo J, Casfont F, de la Peña J, García-Unzueta MT, Amado JÁ, et al. Adrenomedullin in liver transplantation and its relationship with vascular complications. Liver Transpl Surg 1999;5:485–90.10.1002/lt.500050606Search in Google Scholar PubMed

21. Nagasue N, Dhar DK, Yamanoi A, Emi Y, Udagawa J, Yamamoto A, et al. Production and release of endothelin-1 from the gut and spleen in portal hypertension due to cirrhosis. Hepatology 2000;31:1107–14.10.1053/he.2000.6596Search in Google Scholar PubMed

22. Carini R, De Cesaris MG, Splendore R, Domenicotti C, Nitti MP, Pronzato MA, et al. Mechanisms of hepatocyte protection against hypoxic injury by atrial natriuretic peptide. Hepatology 2003;37:277–85.10.1053/jhep.2003.50033Search in Google Scholar PubMed

23. Lainscak M, Haehling S, Anker SD. Natriuretic peptides and other biomarkers in chronic heart failure: from BNP, NT-proBNP, and MR-proANP to routine biochemical markers. Int J Cardiol 2009;132:303–11.10.1016/j.ijcard.2008.11.149http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000263892200003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar PubMed

24. Von HS, Jankowska EA, Morgenthaler NG, Vassanelli C, Zanolla L, Rozentryt P, et al. Comparison of midregional pro-atrial natriuretic peptide with N-terminal pro-B-type natriuretic peptide in predicting survival in patients with chronic heart failure. J Am Coll Cardiol 2007;50:1973–80.10.1016/j.jacc.2007.08.012Search in Google Scholar PubMed

25. Fraser CG, Harris EK. Generation and application of data on biological variation in clinical chemistry. Crit Rev Clin Lab Sci 1989;27:409–37.10.3109/10408368909106595Search in Google Scholar PubMed

26. Ricós C, Alvarez V, Cava F, García-Lario JV, Hernández A, Jiménez CV, et al. Desirable Specifications for imprecision, inaccuracy, and total allowable error, calculated from data on within-subject and between-subject biologic variation. Available from: http://www.westgard.com/biodatabase1.htm. Accessed 13 June, 2012.Search in Google Scholar

27. Ordoñez-Llanos J, Collinson PO, Christenson RH. Amino-terminal pro-B-type natriuretic peptide: analytic considerations. Am J Cardiol 2008;101:9–15.10.1016/j.amjcard.2007.11.013Search in Google Scholar PubMed

28. Wu AH. Serial testing of B-type natriuretic peptide and NT-proBNP for monitoring therapy of heart failure: the role of biologic variation in the interpretation of results. Am Heart J 2006;152:828–34.10.1016/j.ahj.2006.08.021Search in Google Scholar PubMed

29. Bruins S, Fokkema MR, Romer JW, Dejongste MJ, van der Dijs FP, van den Ouweland JM, et al. High intraindividual variation of B-type natriuretic peptide (BNP) and amino-terminal proBNP in patients with stable chronic heart failure. Clin Chem 2004;50:2052–8.10.1373/clinchem.2004.038752Search in Google Scholar PubMed

30. Avello N, Prieto B, Díaz-Molina B, Rodríguez-Lambert JL, Álvarez FV. Clinical utility of NT-proBNP levels in late heart transplantation patients. Clin Chim Acta 2010;411:161–6.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000274102700007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1016/j.cca.2009.10.021Search in Google Scholar PubMed

31. Neuhold S, Huelsmann M, Strunk G, Struck J, Adlbrecht C, Gouya G, et al. Prognostic value of emerging neurohormones in chronic heart failure during optimization of heart failure – specific therapy. Clin Chem 2010;56:121–6.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000273466300018&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1373/clinchem.2009.125856Search in Google Scholar PubMed

32. Brauner JS, Rohde LE, Clausell N. Circulating endothelin-1 and tumor necrosis factor-alpha: early predictors of mortality in patients with septic shock. Intens Care Med 2000;26:305–13.10.1007/s001340051154Search in Google Scholar PubMed

33. Morgenthaler NG, Struck J, Christ-Crain M, Bergmann A, Muller B. Pro-atrial natriuretic peptide is a prognostic marker in sepsis, similar to the APACHE II score: an observational study. Crit Care 2005;9:R37–45.10.1186/cc3015Search in Google Scholar PubMed PubMed Central

34. Suverbiola B, Castellanos-Ortega A, Llorca J, Ortiz F, Iglesias D, Prieto B. Prognostic value of proadrenomedullin in severe sepsis and septic shock patients with community-acquired pneumonia. Swiss Med Wkly 2012;142:w13542.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000301917100006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar

35. Doust JA, Pietrzak E, Dobson A, Glasziou P. How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review. Br Med J 2005;330:625.10.1136/bmj.330.7492.625Search in Google Scholar PubMed PubMed Central

36. Schnabel R, Lubos E, Rupprecht HJ, Espínola-Klein C, Bickel C, Lackner KJ, et al. B-type natriuretic peptide and the risk of cardiovascular events and death in patients with stable angina: results from the Athero Gene study. J Am Coll Cardiol 2006;47:552–8.10.1016/j.jacc.2005.09.039Search in Google Scholar PubMed

37. McKie PM, Rodeheffer RJ, Cataliotti A, Martin FL, Urban LH, Mahoney DW, et al. Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide: biomarkers for mortality in a large community-based cohort free of heart failure. Hypertension 2006;47:874–80.10.1161/01.HYP.0000216794.24161.8cSearch in Google Scholar PubMed PubMed Central

38. Mueller T, Gegenhuber A, Poelz W, Haltmayer M. Diagnosis accuracy of B-type natriuretic peptide and amino terminal proBNP in the emergency diagnosis of heart failure. Heart 2005;91:606–12.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000273735100016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1136/hrt.2004.037762Search in Google Scholar PubMed PubMed Central

39. Januzzi JL Jr., Camargo CA, Anwaruddin S, Baggish AL, Chen AA, Krauser DG, et al. The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study. Am J Cardiol 2005;95:948–54.10.1016/j.amjcard.2004.12.032Search in Google Scholar PubMed

Received: 2012-08-22
Accepted: 2012-11-22
Published Online: 2012-12-08
Published in Print: 2013-06-01

©2013 by Walter de Gruyter Berlin Boston

Articles in the same Issue

  1. Letters to the Editor
  2. Evaluation of a novel room temperature RNA storage tube for use in a real-time quantitative PCR assay
  3. Evaluation of the Universal Master Mix (STAT-NAT DNA-Mix) for reliable molecular testing
  4. HbA1c: performance of the Sebia Capillarys 2 Flex Piercing
  5. A case of monoclonal gammopathy of undetermined significance (MGUS): type IgD-lambda
  6. Evidence-based use of serum protein electrophoresis in laboratory medicine
  7. Plasma volume shifts during multiday racing
  8. Structured handoff at shift change in a clinical laboratory increases patient safety
  9. Instrument-dependent interference of Howell-Jolly bodies in reticulocyte enumeration
  10. Reply to Gore et al.: Plasma volume shift during multiday racing
  11. Recommendations for appropriate serum electrophoresis requests: the Italian approach
  12. Masthead
  13. Masthead
  14. Editorials
  15. Biomarkers for sepsis: an unfinished journey
  16. Laboratory demand management of repetitive testing – time for harmonisation and an evidenced based approach
  17. Reviews
  18. Non-invasive prenatal diagnostics of aneuploidy using next-generation DNA sequencing technologies, and clinical considerations
  19. The diagnostic utility of brain natriuretic peptide in heart failure patients presenting with acute dyspnea: a meta-analysis
  20. Opinion Paper
  21. Opinion paper on innovative approach of biomarkers for infectious diseases and sepsis management in the emergency department
  22. Genetics and Molecular Diagnostics
  23. Microarray with LNA-probes for genotyping of polymorphic variants of Gilbert’s syndrome gene UGT1A1(TA)n
  24. Selection of the optimal manual method of cell free fetal DNA isolation from maternal plasma
  25. A multiplex assay to rapidly exclude HLA-DQ2.5 and HLA-DQ8 expression in patients at risk for celiac disease
  26. Low cost biosensor-based molecular differential diagnosis of α-thalassemia (Southeast Asia deletion)
  27. General Clinical Chemistry and Laboratory Medicine
  28. Managing laboratory test ordering through test frequency filtering
  29. Critical review of laboratory investigations in clinical practice guidelines: proposals for the description of investigation
  30. Long-term stability of laboratory tests and practical implications for quality management
  31. Coffee consumption, serum γ-glutamyltransferase, and glucose tolerance status in middle-aged Japanese men
  32. Biological variation and prognosis usefulness of new biomarkers in liver transplantation
  33. Switching between parathormone (PTH) assays: the impact on the diagnosis of renal osteodystrophy
  34. A comparison between two different in vitro basophil activation tests for gluten- and cow’s milk protein sensitivity in irritable bowel syndrome (IBS)-like patients
  35. A proficiency testing program of hemoglobin analysis in prevention and control of severe hemoglobinopathies in Thailand
  36. Advancing haemostasis automation – successful implementation of robotic centrifugation and sample processing in a tertiary service hospital
  37. ADAM12s and PP13 as first trimester screening markers for adverse pregnancy outcome
  38. Analysis of serous body fluids using the CELL-DYN Sapphire hematology analyzer
  39. Cancer Diagnostics
  40. Association and prognostic value of serum inflammation markers in patients with leukoplakia and oral cavity cancer
  41. Do laboratories follow heart failure recommendations and guidelines and did we improve? The CARdiac MArker Guideline Uptake in Europe (CARMAGUE)
  42. Cardiovascular Diseases
  43. Additional diagnostic and prognostic value of copeptin ultra-sensitive for diagnosis of non-ST-elevation myocardial infarction in older patients presenting to the emergency department1)
  44. Moderate elevations of high-sensitivity cardiac troponin I and B-type natriuretic peptide in chronic hemodialysis patients are associated with mortality
Downloaded on 9.10.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2012-0713/html
Scroll to top button