Chronic antibody-mediated rejection (cAMR) is the main cause of long-term graft loss and presents a diagnostic challenge in renal transplantation medicine. Late-stage diagnosis is made by detecting donor-specific antibodies (DSA) in the blood in combination with typical histomorphological observations on graft biopsy. Leak of non-invasive biomarkers for detection of cAMR permits screening and earlier diagnosis.

In a case control study, urine samples from 18 pediatric patients (mean age 16yrs, range 2–18yrs) were analyzed using capillary electrophoresis together with mass spectrometry. At time of cAMR diagnosis, median time posttransplantation was 5 yrs (range 1–11yrs). Patients were matched with 23 post-kidney transplant pediatric patients without cAMR (no DSA, normal graft biopsy, mean age 16yrs, range 2–18yrs) via the CERTAIN Registry for age, gender, time after transplantation and living donation.

The non-parametric Wilcoxon test was used for statistical analysis, identifying 199 potential biomarkers with an AUC < 0.7 which were then combined in a support vector machine-based classifier. After total cross validation, the accuracy for detection of cAMR was 90.2%, with sensitivity 88.9% and specificity 91.3%. Classifier accuracy was independent of age, gender and GFR. Most peptides of the cAMR-classifier were fragments of the collagen I alpha chain.

This non-invasive test for cAMR is currently ready for prospective validation in large cohorts and for evaluation in longitudinal studies with the aim of identifying those patients who would profit from early graft biopsy and intensification of immunosuppression at an earlier stage after kidney transplantation.

CITATION INFORMATION: Kanzelmeyer N, Zürbig P, Mischack H, Heindl Ruszai K, Seemann T, Hansen M, Henn M, Fichtner A, Toenshoff B, Melk A, Pape L. Urinary Proteomics to Diagnose Chronic-Antibody-Mediated Rejection in Pediatric Kidney Transplantation. Am J Transplant. 2017;17 (suppl 3).

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