Urinary metabolomics for noninvasive detection of antibody-mediated rejection in children after kidney transplantation.

Background: Biomarkers are needed that identify patients with antibody-mediated rejection (ABMR). The goal of this study was to evaluate the utility of urinary metabolomics for early noninvasive detection of ABMR in pediatric kidney transplant recipients. Methods: Urine samples (n=396) from a prospective, observational cohort of 59 renal transplant patients with surveillance or indication biopsies were assayed for 133 unique metabolites by quantitative mass spectrometry. Samples were classified according to Banff criteria for ABMR and partial least squares discriminant analysis was used to identify associated changes in metabolite patterns by creating a composite index based on all 133 metabolites. Results: Urine samples of patients with (n=40) and without ABMR (n=278) were analyzed and a classifier for ABMR was identified (AUC=0.84; 95% CI 0.77-0.91; p=0.006). Application of the classifier to "indeterminate" samples (samples that partially fulfilled Banff criteria for ABMR; n=65) yielded an ABMR score of 0.19+/-0.15, intermediate between scores for ABMR and no ABMR (0.28+/-0.14 and 0.10+/-0.13 respectively, p

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