TY - JOUR
T1 - Real Time Central Assessment of Kidney Transplant Indication Biopsies by Microarrays
T2 - The INTERCOMEX Study
AU - Halloran, P. F.
AU - Reeve, J.
AU - Akalin, E.
AU - Aubert, O.
AU - Bohmig, G. A.
AU - Brennan, D.
AU - Bromberg, J.
AU - Einecke, G.
AU - Eskandary, F.
AU - Gosset, C.
AU - Duong Van Huyen, J. P.
AU - Gupta, G.
AU - Lefaucheur, C.
AU - Malone, A.
AU - Mannon, R. B.
AU - Seron, D.
AU - Sellares, J.
AU - Weir, M.
AU - Loupy, A.
N1 - Funding Information:
This research has been supported by funding and/or resources from One Lambda/Thermo Fisher, and Canada Foundation for Innovation. P.F.H. held a Canada Research Chair in Transplant Immunology until 2008 and currently holds the Muttart Chair in Clinical Immunology.
PY - 2017/11
Y1 - 2017/11
N2 - The authors conducted a prospective trial to assess the feasibility of real time central molecular assessment of kidney transplant biopsy samples from 10 North American or European centers. Biopsy samples taken 1 day to 34 years posttransplantation were stabilized in RNAlater, sent via courier overnight at ambient temperature to the central laboratory, and processed (29 h workflow) using microarrays to assess T cell– and antibody-mediated rejection (TCMR and ABMR, respectively). Of 538 biopsy samples submitted, 519 (96%) were sufficient for microarray analysis (average length, 3 mm). Automated reports were generated without knowledge of histology and HLA antibody, with diagnoses assigned based on Molecular Microscope Diagnostic System (MMDx) classifier algorithms and signed out by one observer. Agreement between MMDx and histology (balanced accuracy) was 77% for TCMR, 77% for ABMR, and 76% for no rejection. A classification tree derived to provide automated sign-outs predicted the observer sign-outs with >90% accuracy. In 451 biopsy samples where feedback was obtained, clinicians indicated that MMDx more frequently agreed with clinical judgment (87%) than did histology (80%) (p = 0.0042). In 81% of feedback forms, clinicians reported that MMDx increased confidence in management compared with conventional assessment alone. The authors conclude that real time central molecular assessment is feasible and offers a useful new dimension in biopsy interpretation. ClinicalTrials.gov NCT#01299168.
AB - The authors conducted a prospective trial to assess the feasibility of real time central molecular assessment of kidney transplant biopsy samples from 10 North American or European centers. Biopsy samples taken 1 day to 34 years posttransplantation were stabilized in RNAlater, sent via courier overnight at ambient temperature to the central laboratory, and processed (29 h workflow) using microarrays to assess T cell– and antibody-mediated rejection (TCMR and ABMR, respectively). Of 538 biopsy samples submitted, 519 (96%) were sufficient for microarray analysis (average length, 3 mm). Automated reports were generated without knowledge of histology and HLA antibody, with diagnoses assigned based on Molecular Microscope Diagnostic System (MMDx) classifier algorithms and signed out by one observer. Agreement between MMDx and histology (balanced accuracy) was 77% for TCMR, 77% for ABMR, and 76% for no rejection. A classification tree derived to provide automated sign-outs predicted the observer sign-outs with >90% accuracy. In 451 biopsy samples where feedback was obtained, clinicians indicated that MMDx more frequently agreed with clinical judgment (87%) than did histology (80%) (p = 0.0042). In 81% of feedback forms, clinicians reported that MMDx increased confidence in management compared with conventional assessment alone. The authors conclude that real time central molecular assessment is feasible and offers a useful new dimension in biopsy interpretation. ClinicalTrials.gov NCT#01299168.
KW - basic (laboratory) research/science
KW - biopsy
KW - clinical research/practice
KW - kidney transplantation/nephrology
KW - microarray/gene array
KW - molecular biology
KW - rejection: T cell mediated (TCMR)
KW - rejection: antibody-mediated (ABMR)
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U2 - 10.1111/ajt.14329
DO - 10.1111/ajt.14329
M3 - Article
C2 - 28449409
AN - SCOPUS:85019989985
SN - 1600-6135
VL - 17
SP - 2851
EP - 2862
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 11
ER -