World Journal of Urology

, Volume 32, Issue 6, pp 1619–1624

Urine protein profiling identified alpha-1-microglobulin and haptoglobin as biomarkers for early diagnosis of acute allograft rejection following kidney transplantation

  • Beatrice Stubendorff
  • Stephanie Finke
  • Martina Walter
  • Olaf Kniemeyer
  • Ferdinand von Eggeling
  • Torsten Gruschwitz
  • Thomas Steiner
  • Undine Ott
  • Gunter Wolf
  • Heiko Wunderlich
  • Kerstin Junker
Original Article

DOI: 10.1007/s00345-014-1263-z

Cite this article as:
Stubendorff, B., Finke, S., Walter, M. et al. World J Urol (2014) 32: 1619. doi:10.1007/s00345-014-1263-z

Abstract

Purpose

Early diagnosis of acute rejection and effective immunosuppressive therapy lead to improvement in graft survival following kidney transplantation. In this study, we aimed to establish a urinary protein profile suitable to distinguish between patients with rejection and stable graft function and to predict acute rejection based on postoperatively collected urine samples. A further objective was to identify candidate proteins for the use as biomarkers in clinical practice.

Methods

Urine samples of 116 kidney recipients were included. Rejection was proven by biopsy (n = 58), and stable transplant function was monitored for at least 2 years (n = 58). Postoperative urine samples were collected between 3rd and 10th day following transplantation. Urinary protein profiles were obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Protein identification and validation were performed using multiplex fluorescence 2DE, peptide mass fingerprinting and enzyme-linked immunosorbent assay.

Results

A protein profile including four mass peaks differentiated acute rejection from stable transplants at the time point of rejection and at the postoperative state with 73 % sensitivity and 88 % specificity. Alpha-1-microglobulin (A1MG) and Haptoglobin (Hp) were identified as putative rejection biomarkers. Protein levels were significantly higher in postoperative urine from patients with rejection (A1MG 29.13 vs. 22.06 μg/ml, p = 0.001; Hp 628.34 vs. 248.57 ng/ml, p = 0.003). The combination of both proteins enabled the diagnosis of early rejection with 85 % sensitivity and 80 % specificity.

Conclusion

Protein profiling using mass spectrometry is suitable for noninvasive detection of rejection-specific changes following kidney transplantation. A specific protein profile enables the prediction of early acute allograft rejection in the immediate postoperative period. A1MG and Hp appear to be reliable rejection biomarkers.

Keywords

Acute rejectionAlpha-1-microglobulinBiomarkerHaptoglobinKidney transplantationProtein profiling

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Beatrice Stubendorff
    • 1
    • 2
  • Stephanie Finke
    • 1
  • Martina Walter
    • 1
  • Olaf Kniemeyer
    • 3
  • Ferdinand von Eggeling
    • 4
  • Torsten Gruschwitz
    • 1
  • Thomas Steiner
    • 1
    • 5
  • Undine Ott
    • 6
    • 7
  • Gunter Wolf
    • 6
    • 7
  • Heiko Wunderlich
    • 1
    • 8
  • Kerstin Junker
    • 1
    • 2
  1. 1.Department of UrologyJena University HospitalJenaGermany
  2. 2.Clinic of Urology and Pediatric UrologySaarland University Medical CenterHomburg/SaarGermany
  3. 3.Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute and Integrated Research and Treatment Center – Center for Sepsis Control and Care (CSCC)Jena University Hospital, Friedrich Schiller UniversityJenaGermany
  4. 4.Institute of Human Genetics, Core Unit Chip Application (CUCA)Jena University HospitalJenaGermany
  5. 5.Department of UrologyHelios Hospital ErfurtErfurtGermany
  6. 6.KfH Kuratorium für Dialyse und Nierentransplantation e.V.KfH NierenzentrumJenaGermany
  7. 7.Department of Internal Medicine IIIJena University HospitalJenaGermany
  8. 8.Clinic of Urology and Pediatric UrologyEisenach St. Georg HospitalEisenachGermany