PURPOSE: Noninvasive diagnosis of acute renal allograft rejection may be advantageous compared with the allograft biopsy. EXPERIMENTAL DESIGN: In this study, a multi-marker classification model for rejection was defined on a training set of 39 allograft patients by statistical comparison of capillary electrophoresis mass spectrometry (CE-MS) peptide spectra in urine samples from 16 cases with subclinical acute T-cell-mediated tubulointerstitial rejection and 23 nonrejection controls. RESULTS: Application of the rejection model to a blinded validation set (n=64) resulted in an AUC value of 0.91 (95% CI: 0.82-0.97, p=0.0001). In total, 16 out of 18 subclinical and 10 out of 10 clinical rejections (BANFF grades Ia/Ib), and 28 out of 36 controls without rejection were correctly classified. Acute tubular injury in the biopsies or concomitant urinary tract infection did not interfere with CE-MS-based diagnosis. Sequence information of identified altered collagen α(I) and α (III) chain fragments in rejection samples suggested an involvement of matrix metalloproteinase-8 (MMP-8). Biopsy stainings revealed matrix metalloproteinase-8 exclusively in neutrophils located within peritubular capillaries and sparsely, in the tubulointerstitium during rejection. CONCLUSIONS AND CLINICAL RELEVANCE: The established marker set contains peptides related to tubulointerstitial infiltration seen in acute rejection. The set of urinary peptide markers will be used for early diagnosis of acute kidney allograft rejection marker in a multicenter phase III prospective study.
PURPOSE: Noninvasive diagnosis of acute renal allograft rejection may be advantageous compared with the allograft biopsy. EXPERIMENTAL DESIGN: In this study, a multi-marker classification model for rejection was defined on a training set of 39 allograft patients by statistical comparison of capillary electrophoresis mass spectrometry (CE-MS) peptide spectra in urine samples from 16 cases with subclinical acute T-cell-mediated tubulointerstitial rejection and 23 nonrejection controls. RESULTS: Application of the rejection model to a blinded validation set (n=64) resulted in an AUC value of 0.91 (95% CI: 0.82-0.97, p=0.0001). In total, 16 out of 18 subclinical and 10 out of 10 clinical rejections (BANFF grades Ia/Ib), and 28 out of 36 controls without rejection were correctly classified. Acute tubular injury in the biopsies or concomitant urinary tract infection did not interfere with CE-MS-based diagnosis. Sequence information of identified altered collagen α(I) and α (III) chain fragments in rejection samples suggested an involvement of matrix metalloproteinase-8 (MMP-8). Biopsy stainings revealed matrix metalloproteinase-8 exclusively in neutrophils located within peritubular capillaries and sparsely, in the tubulointerstitium during rejection. CONCLUSIONS AND CLINICAL RELEVANCE: The established marker set contains peptides related to tubulointerstitial infiltration seen in acute rejection. The set of urinary peptide markers will be used for early diagnosis of acute kidney allograft rejection marker in a multicenter phase III prospective study.
Authors: Trairak Pisitkun; Maria T Gandolfo; Samarjit Das; Mark A Knepper; Serena M Bagnasco Journal: Proteomics Clin Appl Date: 2012-06 Impact factor: 3.494
Authors: Hector R Wong; Natalie Z Cvijanovich; Nick Anas; Geoffrey L Allen; Neal J Thomas; Michael T Bigham; Scott L Weiss; Julie Fitzgerald; Paul A Checchia; Keith Meyer; Thomas P Shanley; Michael Quasney; Mark Hall; Rainer Gedeit; Robert J Freishtat; Jeffrey Nowak; Shekhar S Raj; Shira Gertz; Emily Dawson; Kelli Howard; Kelli Harmon; Patrick Lahni; Erin Frank; Kimberly W Hart; Christopher J Lindsell Journal: Crit Care Med Date: 2015-08 Impact factor: 7.598
Authors: Rubin Zhang; Min Li; Kanwaljit K Chouhan; Eric E Simon; Lotuce Lee Hamm; Vecihil Batuman Journal: Clin Transplant Date: 2013-10-26 Impact factor: 2.863