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

Authors

  • Beatrice Stubendorff
    • Department of UrologyJena University Hospital
    • Clinic of Urology and Pediatric UrologySaarland University Medical Center
  • Stephanie Finke
    • Department of UrologyJena University Hospital
  • Martina Walter
    • Department of UrologyJena University Hospital
  • Olaf Kniemeyer
    • 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 University
  • Ferdinand von Eggeling
    • Institute of Human Genetics, Core Unit Chip Application (CUCA)Jena University Hospital
  • Torsten Gruschwitz
    • Department of UrologyJena University Hospital
  • Thomas Steiner
    • Department of UrologyJena University Hospital
    • Department of UrologyHelios Hospital Erfurt
  • Undine Ott
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V.KfH Nierenzentrum
    • Department of Internal Medicine IIIJena University Hospital
  • Gunter Wolf
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V.KfH Nierenzentrum
    • Department of Internal Medicine IIIJena University Hospital
  • Heiko Wunderlich
    • Department of UrologyJena University Hospital
    • Clinic of Urology and Pediatric UrologyEisenach St. Georg Hospital
    • Department of UrologyJena University Hospital
    • Clinic of Urology and Pediatric UrologySaarland University Medical Center
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