Urine Protein Profiling Identified alpha-1-microglobulin and Haptoglobin as Biomarkers for Early Diagnosis of Acute Allograft Rejection Following Kidney Transplantation

World J Urol. 2014 Dec;32(6):1619-24. doi: 10.1007/s00345-014-1263-z. Epub 2014 Feb 19.


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.

MeSH terms

  • Adult
  • Alpha-Globulins / urine*
  • Biomarkers / urine
  • Cohort Studies
  • Early Diagnosis
  • Female
  • Graft Rejection / diagnosis*
  • Graft Rejection / urine*
  • Haptoglobins / urine*
  • Humans
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • ROC Curve
  • Renal Insufficiency / diagnosis
  • Renal Insufficiency / surgery
  • Renal Insufficiency / urine*


  • Alpha-Globulins
  • Biomarkers
  • Haptoglobins
  • alpha-1-microglobulin