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

作者：Stubendorff Beatrice; Finke Stephanie; Walter Martina; Kniemeyer Olaf; von Eggeling Ferdinand; Gruschwitz Torsten; Steiner Thomas; Ott Undine; Wolf Gunter; Wunderlich Heiko; Junker Kerstin^*

来源：World Journal of Urology, 2014, 32(6): 1619-1624.

DOI：10.1007/s00345-014-1263-z

• Acute rejection
• Alpha-1-microglobulin
• Biomarker
• Haptoglobin
• Kidney transplantation
• Protein profiling

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. %26lt;br%26gt;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. %26lt;br%26gt;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 mu g/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. %26lt;br%26gt;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.

• 出版日期2014-12