A Peripheral Blood Diagnostic Test for Acute Rejection in Renal Transplantation |
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| Authors: | T. Tran L. Ying M. J. Vitalone A. Chen S. Hsieh H. Dai M. Zhang M. Naesens V. Zarkhin P. Sansanwal R. Chen M. Mindrinos W. Xiao M. Benfield R. B. Ettenger V. Dharnidharka R. Mathias A. Portale R. McDonald W. Harmon D. Kershaw V. M. Vehaskari E. Kamil H. J. Baluarte B. Warady R. Davis A. J. Butte O. Salvatierra M. M. Sarwal |
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| Affiliation: | 1. California Pacific Medical Center, Research Institute, San Francisco, CA;2. Department of Pediatrics, Stanford University, CA;3. Department of Biochemistry, Stanford University, CA;4. Massachusetts General Hospital, Harvard Medical School, MA;5. Pediatric Nephrology, University of Alabama at Birmingham, AL;6. Division of Nephrology, Department of Pediatrics, David Geffen School of Medicine at UCLA, UCLA Children's Health Center, University of California Los Angeles, CA;7. Department of Pediatrics Nephrology, University of Florida College of Medicine & Shands Children's Hospital, Gainesville, FL;8. Pediatric Nephrology, Nemours Children's Clinic Orlando, FL;9. Department of Pediatrics, University of California San Francisco, CA;10. Children's Hospital & Regional Medical Center Seattle, WA;11. Department of Pediatrics, Harvard University, MA;12. Department of Pediatrics, University of Michigan, MI;13. Department of Pediatrics, University of Louisiana Health Sciences Center, LA;14. Cedars‐Sinai Medical Center, Los Angeles, CA;15. The Children's Hospital of Philadelphia, Philadelphia, PA;16. Children's Mercy Hospital, Kansas City, MO;17. Department of Surgery, Stanford University, CA |
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| Abstract: | ![]()
Monitoring of renal graft status through peripheral blood (PB) rather than invasive biopsy is important as it will lessen the risk of infection and other stresses, while reducing the costs of rejection diagnosis. Blood gene biomarker panels were discovered by microarrays at a single center and subsequently validated and cross‐validated by QPCR in the NIH SNSO1 randomized study from 12 US pediatric transplant programs. A total of 367 unique human PB samples, each paired with a graft biopsy for centralized, blinded phenotype classification, were analyzed (115 acute rejection (AR), 180 stable and 72 other causes of graft injury). Of the differentially expressed genes by microarray, Q‐PCR analysis of a five gene‐set (DUSP1, PBEF1, PSEN1, MAPK9 and NKTR) classified AR with high accuracy. A logistic regression model was built on independent training‐set (n = 47) and validated on independent test‐set (n = 198)samples, discriminating AR from STA with 91% sensitivity and 94% specificity and AR from all other non‐AR phenotypes with 91% sensitivity and 90% specificity. The 5‐gene set can diagnose AR potentially avoiding the need for invasive renal biopsy. These data support the conduct of a prospective study to validate the clinical predictive utility of this diagnostic tool. |
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| Keywords: | Acute allograft rejection biomarker bioinformatics renal allograft rejection renal transplantation transplantation transplantation genomics transplant rejection translational research |
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