Real Time Central Assessment of Kidney Transplant Indication Biopsies by Microarrays: The INTERCOMEX Study

P. F. Halloran, J. Reeve, Enver Akalin, O. Aubert, G. A. Bohmig, D. Brennan, J. Bromberg, G. Einecke, F. Eskandary, C. Gosset, J. P. Duong Van Huyen, G. Gupta, C. Lefaucheur, A. Malone, R. B. Mannon, D. Seron, J. Sellares, M. Weir, A. Loupy

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Transplantation
DOIs
StateAccepted/In press - 2017

Fingerprint

Transplants
Kidney
Biopsy
Histology
Molecular Pathology
Workflow
Antibodies
Microarray Analysis
T-Lymphocytes
Temperature
Rejection (Psychology)

Keywords

  • Basic (laboratory) research/science
  • Biopsy
  • Clinical research/practice
  • Kidney transplantation/nephrology
  • Microarray/gene array
  • Molecular biology
  • Rejection: antibody-mediated (ABMR)
  • Rejection: T cell mediated (TCMR)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

Real Time Central Assessment of Kidney Transplant Indication Biopsies by Microarrays : The INTERCOMEX Study. / Halloran, P. F.; Reeve, J.; Akalin, Enver; Aubert, O.; Bohmig, G. A.; Brennan, D.; Bromberg, J.; Einecke, G.; Eskandary, F.; Gosset, C.; Duong Van Huyen, J. P.; Gupta, G.; Lefaucheur, C.; Malone, A.; Mannon, R. B.; Seron, D.; Sellares, J.; Weir, M.; Loupy, A.

In: American Journal of Transplantation, 2017.

Research output: Contribution to journalArticle

Halloran, PF, Reeve, J, Akalin, E, Aubert, O, Bohmig, GA, Brennan, D, Bromberg, J, Einecke, G, Eskandary, F, Gosset, C, Duong Van Huyen, JP, Gupta, G, Lefaucheur, C, Malone, A, Mannon, RB, Seron, D, Sellares, J, Weir, M & Loupy, A 2017, 'Real Time Central Assessment of Kidney Transplant Indication Biopsies by Microarrays: The INTERCOMEX Study', American Journal of Transplantation. https://doi.org/10.1111/ajt.14329
Halloran, P. F. ; Reeve, J. ; Akalin, Enver ; Aubert, O. ; Bohmig, G. A. ; Brennan, D. ; Bromberg, J. ; Einecke, G. ; Eskandary, F. ; Gosset, C. ; Duong Van Huyen, J. P. ; Gupta, G. ; Lefaucheur, C. ; Malone, A. ; Mannon, R. B. ; Seron, D. ; Sellares, J. ; Weir, M. ; Loupy, A. / Real Time Central Assessment of Kidney Transplant Indication Biopsies by Microarrays : The INTERCOMEX Study. In: American Journal of Transplantation. 2017.
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abstract = "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.",
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AU - Halloran, P. F.

AU - Reeve, J.

AU - Akalin, Enver

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.

PY - 2017

Y1 - 2017

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.

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KW - Kidney transplantation/nephrology

KW - Microarray/gene array

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KW - Rejection: antibody-mediated (ABMR)

KW - Rejection: T cell mediated (TCMR)

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