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Clinical and Analytical Validation of a Novel Urine-Based Test for the Detection of Allograft Rejection in Renal Transplant Patients

In this clinical validation study, we developed and validated a urinary Q-Score generated from the quantitative test QSant, formerly known as QiSant, for the detection of biopsy-confirmed acute rejection in kidney transplants. Using a cohort of 223 distinct urine samples collected from three indepen...

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Autores principales: Nolan, Niamh, Valdivieso, Katherine, Mani, Rekha, Yang, Joshua Y. C., Sarwal, Reuben D., Katzenbach, Phoebe, Chalasani, Kavita, Hongo, Donna, Lugtu, Gladys, Mark, Corinne, Chen, Edna, Nijor, Reggie, Savoca, David, Wexler, David S., Whitson, Todd, Huang, Shih-Jwo, Lu, Lucy H., Zawada, Robert J. X., Hytopoulos, Evangelos, Sarwal, Minnie M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465561/
https://www.ncbi.nlm.nih.gov/pubmed/32707779
http://dx.doi.org/10.3390/jcm9082325
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author Nolan, Niamh
Valdivieso, Katherine
Mani, Rekha
Yang, Joshua Y. C.
Sarwal, Reuben D.
Katzenbach, Phoebe
Chalasani, Kavita
Hongo, Donna
Lugtu, Gladys
Mark, Corinne
Chen, Edna
Nijor, Reggie
Savoca, David
Wexler, David S.
Whitson, Todd
Huang, Shih-Jwo
Lu, Lucy H.
Zawada, Robert J. X.
Hytopoulos, Evangelos
Sarwal, Minnie M.
author_facet Nolan, Niamh
Valdivieso, Katherine
Mani, Rekha
Yang, Joshua Y. C.
Sarwal, Reuben D.
Katzenbach, Phoebe
Chalasani, Kavita
Hongo, Donna
Lugtu, Gladys
Mark, Corinne
Chen, Edna
Nijor, Reggie
Savoca, David
Wexler, David S.
Whitson, Todd
Huang, Shih-Jwo
Lu, Lucy H.
Zawada, Robert J. X.
Hytopoulos, Evangelos
Sarwal, Minnie M.
author_sort Nolan, Niamh
collection PubMed
description In this clinical validation study, we developed and validated a urinary Q-Score generated from the quantitative test QSant, formerly known as QiSant, for the detection of biopsy-confirmed acute rejection in kidney transplants. Using a cohort of 223 distinct urine samples collected from three independent sites and from both adult and pediatric renal transplant patients, we examined the diagnostic utility of the urinary Q-Score for detection of acute rejection in renal allografts. Statistical models based upon the measurements of the six QSant biomarkers (cell-free DNA, methylated-cell-free DNA, clusterin, CXCL10, creatinine, and total protein) generated a renal transplant Q-Score that reliably differentiated stable allografts from acute rejections in both adult and pediatric renal transplant patients. The composite Q-Score was able to detect both T cell-mediated rejection and antibody-mediated rejection patients and differentiate them from stable non-rejecting patients with a receiver–operator characteristic curve area under the curve of 99.8% and an accuracy of 98.2%. Q-Scores < 32 indicated the absence of active rejection and Q-Scores ≥ 32 indicated an increased risk of active rejection. At the Q-Score cutoff of 32, the overall sensitivity was 95.8% and specificity was 99.3%. At a prevalence of 25%, positive and negative predictive values for active rejection were 98.0% and 98.6%, respectively. The Q-Score also detected subclinical rejection in patients without an elevated serum creatinine level but identified by a protocol biopsy. This study confirms that QSant is an accurate and quantitative measurement suitable for routine monitoring of renal allograft status.
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spelling pubmed-74655612020-09-04 Clinical and Analytical Validation of a Novel Urine-Based Test for the Detection of Allograft Rejection in Renal Transplant Patients Nolan, Niamh Valdivieso, Katherine Mani, Rekha Yang, Joshua Y. C. Sarwal, Reuben D. Katzenbach, Phoebe Chalasani, Kavita Hongo, Donna Lugtu, Gladys Mark, Corinne Chen, Edna Nijor, Reggie Savoca, David Wexler, David S. Whitson, Todd Huang, Shih-Jwo Lu, Lucy H. Zawada, Robert J. X. Hytopoulos, Evangelos Sarwal, Minnie M. J Clin Med Article In this clinical validation study, we developed and validated a urinary Q-Score generated from the quantitative test QSant, formerly known as QiSant, for the detection of biopsy-confirmed acute rejection in kidney transplants. Using a cohort of 223 distinct urine samples collected from three independent sites and from both adult and pediatric renal transplant patients, we examined the diagnostic utility of the urinary Q-Score for detection of acute rejection in renal allografts. Statistical models based upon the measurements of the six QSant biomarkers (cell-free DNA, methylated-cell-free DNA, clusterin, CXCL10, creatinine, and total protein) generated a renal transplant Q-Score that reliably differentiated stable allografts from acute rejections in both adult and pediatric renal transplant patients. The composite Q-Score was able to detect both T cell-mediated rejection and antibody-mediated rejection patients and differentiate them from stable non-rejecting patients with a receiver–operator characteristic curve area under the curve of 99.8% and an accuracy of 98.2%. Q-Scores < 32 indicated the absence of active rejection and Q-Scores ≥ 32 indicated an increased risk of active rejection. At the Q-Score cutoff of 32, the overall sensitivity was 95.8% and specificity was 99.3%. At a prevalence of 25%, positive and negative predictive values for active rejection were 98.0% and 98.6%, respectively. The Q-Score also detected subclinical rejection in patients without an elevated serum creatinine level but identified by a protocol biopsy. This study confirms that QSant is an accurate and quantitative measurement suitable for routine monitoring of renal allograft status. MDPI 2020-07-22 /pmc/articles/PMC7465561/ /pubmed/32707779 http://dx.doi.org/10.3390/jcm9082325 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nolan, Niamh
Valdivieso, Katherine
Mani, Rekha
Yang, Joshua Y. C.
Sarwal, Reuben D.
Katzenbach, Phoebe
Chalasani, Kavita
Hongo, Donna
Lugtu, Gladys
Mark, Corinne
Chen, Edna
Nijor, Reggie
Savoca, David
Wexler, David S.
Whitson, Todd
Huang, Shih-Jwo
Lu, Lucy H.
Zawada, Robert J. X.
Hytopoulos, Evangelos
Sarwal, Minnie M.
Clinical and Analytical Validation of a Novel Urine-Based Test for the Detection of Allograft Rejection in Renal Transplant Patients
title Clinical and Analytical Validation of a Novel Urine-Based Test for the Detection of Allograft Rejection in Renal Transplant Patients
title_full Clinical and Analytical Validation of a Novel Urine-Based Test for the Detection of Allograft Rejection in Renal Transplant Patients
title_fullStr Clinical and Analytical Validation of a Novel Urine-Based Test for the Detection of Allograft Rejection in Renal Transplant Patients
title_full_unstemmed Clinical and Analytical Validation of a Novel Urine-Based Test for the Detection of Allograft Rejection in Renal Transplant Patients
title_short Clinical and Analytical Validation of a Novel Urine-Based Test for the Detection of Allograft Rejection in Renal Transplant Patients
title_sort clinical and analytical validation of a novel urine-based test for the detection of allograft rejection in renal transplant patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465561/
https://www.ncbi.nlm.nih.gov/pubmed/32707779
http://dx.doi.org/10.3390/jcm9082325
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