Open AccessUrinary proteomics to diagnose chronic active antibody‐mediated rejection in pediatric kidney transplantation – a pilot study
Author(s) -
Kanzelmeyer Nele Kirsten,
Zürbig Petra,
Mischak Harald,
Metzger Jochen,
Fichtner Alexander,
Ruszai Kristzina Heindl,
Seemann Tomas,
Hansen Matthias,
Wygoda Simone,
Krupka Kai,
Tönshoff Burkhard,
Melk Anette,
Pape Lars
Publication year - 2019
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/tri.13363
Subject(s) - medicine , receiver operating characteristic , urinary system , kidney transplantation , transplantation , biomarker , urology , nephrology , area under the curve , gastroenterology , pathology , biochemistry , chemistry
Summary Chronic antibody‐mediated rejection ( cABMR ) is the main cause of long‐term renal graft loss. Late‐stage diagnosis is made by detecting donor‐specific antibodies ( DSA ) in blood combined with typical histomorphological lesions in renal allografts. There is a need for noninvasive biomarkers for cABMR that might permit screening and earlier diagnosis. In a case control study of 24 pediatric renal transplant recipients, urine samples were analyzed using capillary electrophoresis and mass spectrometry. Patients were matched with 36 pediatric renal transplant patients without cABMR . Statistical analysis used the nonparametric Wilcoxon test to identify 79 significant biomarkers, which were combined to a support vector machine‐based classifier. After validation in an independent test cohort of eight pediatric patients with and 12 without cABMR , the area under the receiver operating characteristic ( ROC ) curve ( AUC ) for detection of cABMR was 0.92 (95% CI 0.71–0.99) with a sensitivity of 100% (95% CI 63–100%) and a specificity of 75% (95% CI 43–95%). Combining this classifier with the urinary proteomic marker CKD 273 improved the detection of patients with cABMR with misclassification in only 2/20 of the patients. These data indicate that a biomarker pattern derived from urinary proteomics allows the detection of cABMR in pediatric renal transplant recipients with high sensitivity and moderate specificity.