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Expanding the Non-Invasive Diagnosis of Acute Rejection in Kidney Transplants Through Detection of Donor-Derived DNA in Urine: Proof-of-Concept Study

Authors
 Jieun Kim  ;  Dong-Moung Kim  ;  Yu Jin Park  ;  Seung-Tae Lee  ;  Hyon-Suk Kim  ;  Myoung Soo Kim  ;  Beom Seok Kim  ;  Jong Rak Choi 
Citation
 ANNALS OF LABORATORY MEDICINE, Vol.41(5) : 469-478, 2021-09 
Journal Title
ANNALS OF LABORATORY MEDICINE
ISSN
 2234-3806 
Issue Date
2021-09
Keywords
Acute rejection ; Donor-derived DNA ; Kidney transplantation ; Next-generation sequencing ; Single-nucleotide variants ; Urine
Abstract
Background: Approximately 10%-20% of kidney transplant (KT) recipients suffer from acute rejection (AR); thus, sensitive and accurate monitoring of allograft status is recommended. We evaluated the clinical utility of donor-derived DNA (dd-DNA) detection in the urine of KT recipients as a non-invasive means for diagnosing AR. Methods: Urine samples serially collected from 39 KT recipients were tested for 39 single-nucleotide variant loci selected according to technical criteria (i.e., high minor allele frequency and low analytical error) using next-generation sequencing. The fraction of dd-DNA was calculated and normalized by the urine creatinine (UCr) level (%dd-DNA/UCr). The diagnostic performance of %dd-DNA/UCr for AR was assessed by ROC curve analysis. Results: There was an increasing trend of %dd-DNA/UCr in the AR group before subsequent graft injury, which occurred before (median of 52 days) histological rejection. The serum creatinine (SCr) level differed significantly between the AR and non-AR groups at two and four months of follow-up, whereas %dd-DNA/UCr differed between the groups at six months of follow-up. The combination of %dd-DNA/UCr, SCr, and spot urine protein (UPtn)/UCr showed high discriminating power, with an area under the ROC curve of 0.93 (95% confidence interval: 0.81-1.00) and a high negative predictive value of 100.0%. Conclusions: Although the dd-DNA-based test cannot eliminate the need for biopsy, the high negative predictive value of this marker could increase the prebiopsy probability of detecting treatable injury to make biopsy an even more effective diagnostic tool.
Files in This Item:
T202101619.pdf Download
DOI
10.3343/alm.2021.41.5.469
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Myoung Soo(김명수) ORCID logo https://orcid.org/0000-0002-8975-8381
Kim, Beom Seok(김범석) ORCID logo https://orcid.org/0000-0002-5732-2583
Lee, Seung-Tae(이승태) ORCID logo https://orcid.org/0000-0003-1047-1415
Choi, Jong Rak(최종락) ORCID logo https://orcid.org/0000-0002-0608-2989
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/183962
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