@article{32c535f51e5644a49c088ba37f4b9676,
title = "Development and clinical validity of a novel blood-based molecular biomarker for subclinical acute rejection following kidney transplant",
abstract = "Noninvasive biomarkers are needed to monitor stable patients after kidney transplant (KT), because subclinical acute rejection (subAR), currently detectable only with surveillance biopsies, can lead to chronic rejection and graft loss. We conducted a multicenter study to develop a blood-based molecular biomarker for subAR using peripheral blood paired with surveillance biopsies and strict clinical phenotyping algorithms for discovery and validation. At a predefined threshold, 72% to 75% of KT recipients achieved a negative biomarker test correlating with the absence of subAR (negative predictive value: 78%-88%), while a positive test was obtained in 25% to 28% correlating with the presence of subAR (positive predictive value: 47%-61%). The clinical phenotype and biomarker independently and statistically correlated with a composite clinical endpoint (renal function, biopsy-proved acute rejection, ≥grade 2 interstitial fibrosis, and tubular atrophy), as well as with de novo donor-specific antibodies. We also found that <50% showed histologic improvement of subAR on follow-up biopsies despite treatment and that the biomarker could predict this outcome. Our data suggest that a blood-based biomarker that reduces the need for the indiscriminate use of invasive surveillance biopsies and that correlates with transplant outcomes could be used to monitor KT recipients with stable renal function, including after treatment for subAR, potentially improving KT outcomes.",
keywords = "alloantibody, biomarker, clinical research/practice, clinical trial, genomics, kidney transplantation/nephrology, rejection: subclinical, translational research/science",
author = "{the Clinical Trials in Organ Transplantation 08 (CTOT-08)} and Friedewald, {John J.} and Kurian, {Sunil M.} and Heilman, {Raymond L.} and Whisenant, {Thomas C.} and Poggio, {Emilio D.} and Christopher Marsh and Prabhakar Baliga and Jonah Odim and Brown, {Merideth M.} and Ikle, {David N.} and Armstrong, {Brian D.} and charette, {jane I.} and Brietigam, {Susan S.} and Nedjema Sustento-Reodica and Lihui Zhao and Manoj Kandpal and Salomon, {Daniel R.} and Abecassis, {Michael M.}",
note = "Funding Information: Correspondence: Michael M. Abecassis, Comprehensive Transplant Center, Departments of Surgery and Microbiology‐ Immunology, Northwestern Feinberg School of Medicine, 676 N St Clair St, Suite 1900, Chicago, IL 60611 Email: mabecass@nm.org Funding information We also acknowledge financial support in the form of grants from the National Institutes of Health (U01 AI084146, 3 U01 AI063594‐07S1, 1U01AI088635, 2U19 AI063603, R34 AI118493) and from Transplant Genomics Inc, as well as from NU to the Comprehensive Transplant Center. Funding Information: Funding information We also acknowledge financial support in the form of grants from the National Institutes of Health (U01 AI084146, 3 U01 AI063594-07S1, 1U01AI088635, 2U19 AI063603, R34 AI118493) and from Transplant Genomics Inc, as well as from NU to the Comprehensive Transplant Center. We would like to acknowledge our patients, transplant coordinators, research services cores and the many care providers at each transplant center who helped achieve the successful completion of the CTOT-08 study. Specifically, Michael Leonard (Mayo Scottsdale), Jennifer Czerr (Cleveland Clinic), Gail Johnson and Christina Hurman (MUSC), Jaquelene Peysakhovich (Northwestern University), and Shannon Mount and Michele Meyer (Scripps Health) were instrumental in helping us achieve enrollment and capture of data and samples. We thank Drs Richard H. Scheuermann and Brian D. Aevermann (Craig Venter Institute, La Jolla, CA) for their guidance on biomarker development and validation. We also thank the CTOT Steering Committee for their guidance in protocol development, monitoring of study outcomes, and review of the data. We also thank the CTOT Steering Committee, particularly Dr Nancy D. Bridges (National Institute of Allergy and Infectious Diseases), for their guidance in protocol development, monitoring of study outcomes, and review of the data. Publisher Copyright: {\textcopyright} 2018 The American Society of Transplantation and the American Society of Transplant Surgeons",
year = "2019",
month = jan,
doi = "10.1111/ajt.15011",
language = "English (US)",
volume = "19",
pages = "98--109",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley-Blackwell",
number = "1",
}