ESPN 50th Annual Meeting

ESPN 2017


 
Urinary Proteomics to diagnose chronic-antibody-mediated rejection in pediatric kidney transplantation
NELE KANZELMEYER 1 PETRA ZÜRBIG 2 HARALD MISCHAK 2 KRISTZINA HEIDEL-RUSZAI 3 TOMAS SEEMANN 4 MATTHIAS HANSEN 5 ALEXANDER FICHTNER 6 BURKHARD TOENSHOFF 6 ANETTE MELK 1 LARS PAPE 1

1- DEPARTMENT OF PEDIARIC NEPHROLOGY, HANNOVER MEDICAL SCHOOL
2- MOSAIQUES DIAGNOSTICS
3- DEPARTMENT OF PEDIATRIC NEPHROLOGY, UNIVERSITY HOSPITAL OF VIENNA
4- DEPARTMENT OF PEDIATRIC NEPHROLOGY, UNIVERSITY HOSPITAL OF PRAGUE
5- CLEMENTINE KINDERHOSPITAL, FRANKFURT
6- DEPARTMENT OF PEDIATRIC I, UNIVERSTITY, CHILDRENS’ HOSPITAL, HEIDELBERG
 
Introduction:

Chronic antibody mediated rejection (cAMR) is the main cause of long-term graft loss and a diagnostic challenge in renal transplantation medicine. Actually it is diagnosed in late stages by detecting donor-specific antibodies (DSA) in the blood in combination with observing typical histomorphological findings in graft biopsy. There is a leak of non-invasive biomarkers for detection of CHR allowing screening and earlier diagnosis.

Material and methods:

In a case-control-study, urine samples were analysed with capillary electrophoresis coupled to mass spectrometry of 18 pediatric patients at time of diagnosis of cAMR, distinguishing from 23 pediatric patients after kidney transplantation without cAMR (no DSA, normal graft biopsy) who were matched vie the Certain-Registry for age, gender, time after transplantation and living donation.

Results:

After statistical analysis with the non-parametric Wilcoxon test, 199 potential biomarkers were identified with an AUC < 0.7. These biomarkers were combined in a support vector machine (SVM)-based classifier. After total cross validation, the accuracy for detection cAMR was 90.2%. Sensitivity was 88.9% and specificity 91.3%. Th classifier’s accuracy was independent of age, gender and glomerular filtration rate. Most peptides of this cAMP-classifier were fragments of the collagen I alpha chain.

Conclusions:

This test should be validated in large cohorts evaluated in longitudinal studies with the aim to identify those patients after kidney transplantation, who would profit from early graft biopsy and intensification of immunosuppression at an earlier stage.