Abstract

improvements in graft survival following kidney transplantation. However, there are no non-invasive diagnostic parameters available that enable early and reliable detection of acute rejection. The objective of our study was to establish a urinary protein profile suitable to determine rejectionspecific changes following kidney transplantation and to predict early acute rejection at a postoperative stage. Furthermore, we focused on identification of candidate proteins for the use as biomarkers in clinical practice for diagnosis of acute rejection. METHODS: Urine samples of 116 kidney recipients were included. Rejection was proven by biopsy (n1⁄458) and stable transplant function was monitored for at least 2 years (n1⁄458). Postoperative urine samples were collected between 3rd and 10th day following transplantation. Urinary protein profiles were analyzed by SELDI-TOF-MS. Multiplex-Fluorescence-2DE and Peptide Mass Fingerprinting were used for identification of candidate proteins. Urinary concentration of candidate proteins was validated by ELISA. RESULTS: A protein signature including 4 masses differentiated acute rejection from stable transplant patients at the postoperative stage with 73% sensitivity and 88% specificity. Alpha-1-microglobulin (A1MG) and Haptoglobin (Hp) were identified as putative biomarkers for acute rejection. Protein levels were significantly higher in postoperative urine samples from patients with upcoming rejection than in stable transplant patients (A1MG: 29.13 mg/ml vs. 22.06 mg/ml, p1⁄40.001; Hp: 628.34 ng/ml vs. 248.57 ng/ml, p1⁄40.003). The combination of both proteins enabled the diagnosis of early rejection with 85% sensitivity and 80% specificity. CONCLUSIONS: Protein profiling using mass spectrometry is suitable for non-invasive detection of rejection-specific changes following kidney transplantation. A specific protein profile enables prediction of early acute allograft rejection in the immediate postoperative period. A1MG and Hp appear to be reliable rejection biomarkers. Further analyses have to show if early diagnosis is possible for patients with allograft rejection that occurs several month after transplantation by analyzing changes in urine protein pattern in regular intervals.

Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call