Development and clinical validity of a novel blood‐based molecular biomarker for subclinical acute rejection following kidney transplant

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 molecu...

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Bibliographic Details
Published in:	American journal of transplantation 2019-01, Vol.19 (1), p.98-109
Main Authors:	Friedewald, John J., Kurian, Sunil M., Heilman, Raymond L., Whisenant, Thomas C., Poggio, Emilio D., Marsh, Christopher, Baliga, Prabhakar, Odim, Jonah, Brown, Merideth M., Ikle, David N., Armstrong, Brian D., charette, jane I., Brietigam, Susan S., Sustento‐Reodica, Nedjema, Zhao, Lihui, Kandpal, Manoj, Salomon, Daniel R., Abecassis, Michael M.
Format:	Article
Language:	eng
Subjects:	Adult Aged Algorithms alloantibody Atrophy biomarker Biomarkers Biomarkers - blood Biopsy clinical research/practice clinical trial Female Fibrosis Fibrosis - diagnosis genomics Glomerular Filtration Rate Graft rejection Graft Rejection - blood Graft Rejection - diagnosis Graft Survival Health surveillance Humans Kidney Transplantation kidney transplantation/nephrology Kidneys Male Middle Aged Peripheral blood Phenotype Phenotypes Phenotyping Predictive Value of Tests rejection: subclinical Renal function translational research/science Treatment Outcome Young Adult
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Summary:	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
ISSN:	1600-6135 1600-6143