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

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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Bibliographic Details
Published in:Journal of clinical medicine Vol. 9; no. 8; p. 2325
Main Authors: 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.
Format: Journal Article
Language:English
Published: Basel MDPI AG 22-07-2020
MDPI
Subjects:
Biomarkers
Biopsy
Clinical medicine
Creatinine
Kidney diseases
Kidney transplants
Pediatrics
Surveillance
Urine
Validation studies
Istanbul Turkey
San Francisco California
Turkey
California
United States > US
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Summary: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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ISSN:2077-0383
2077-0383
DOI:10.3390/jcm9082325