Expanding the Non-Invasive Diagnosis of Acute Rejection in Kidney Transplants Through Detection of Donor-Derived DNA in Urine: Proof-of-Concept Study
| العنوان: | Expanding the Non-Invasive Diagnosis of Acute Rejection in Kidney Transplants Through Detection of Donor-Derived DNA in Urine: Proof-of-Concept Study |
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| المؤلفون: | Yu Jin Park, Jieun Kim, Dong-Moung Kim, Jong Rak Choi, Hyon Suk Kim, Seung-Tae Lee, Beom Seok Kim, Myoung Soo Kim |
| المصدر: | Annals of Laboratory Medicine |
| بيانات النشر: | Annals of Laboratory Medicine, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Graft Rejection, Male, 0301 basic medicine, medicine.medical_specialty, Donor-derived DNA, Clinical Biochemistry, Urology, Urine, 030230 surgery, Kidney transplant, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Biopsy, Single-nucleotide variants, medicine, Humans, Kidney transplantation, Kidney, Creatinine, medicine.diagnostic_test, business.industry, Biochemistry (medical), DNA, General Medicine, medicine.disease, Kidney Transplantation, Tissue Donors, Confidence interval, Minor allele frequency, 030104 developmental biology, medicine.anatomical_structure, chemistry, Next-generation sequencing, Acute rejection, Original Article, business, Diagnostic Genetics, Biomarkers |
| الوصف: | 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. |
| تدمد: | 2234-3814 2234-3806 |
| DOI: | 10.3343/alm.2021.41.5.469 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a6d423ad10836d70ce0bcf153f80c2f6 https://doi.org/10.3343/alm.2021.41.5.469 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a6d423ad10836d70ce0bcf153f80c2f6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22343814 22343806 |
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| DOI: | 10.3343/alm.2021.41.5.469 |