Cell-Free Mitochondrial DNA: An Upcoming Non-Invasive Tool for Diagnosis of BK Polyomavirus-Associated Nephropathy

Mitochondria are essential organelles that possess their own DNA. Mitochondrial dysfunction has been revealed in many kidney diseases, including BK polyomavirus-associated nephropathy (BKPyVAN). In this study, we introduce an innovative approach for non-invasive monitoring of mitochondrial impairmen...

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Main Authors: Luying Guo, Sulin Luo, Xingxia Wang, Nengbo Zhang, Yamei Cheng, Jia Shen, Jianghua Chen, Rending Wang
Format: Article
Language:English
Published: MDPI AG 2024-03-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/14/3/348
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author Luying Guo
Sulin Luo
Xingxia Wang
Nengbo Zhang
Yamei Cheng
Jia Shen
Jianghua Chen
Rending Wang
author_facet Luying Guo
Sulin Luo
Xingxia Wang
Nengbo Zhang
Yamei Cheng
Jia Shen
Jianghua Chen
Rending Wang
author_sort Luying Guo
collection DOAJ
description Mitochondria are essential organelles that possess their own DNA. Mitochondrial dysfunction has been revealed in many kidney diseases, including BK polyomavirus-associated nephropathy (BKPyVAN). In this study, we introduce an innovative approach for non-invasive monitoring of mitochondrial impairment through urinary donor-derived cell-free mitochondrial DNA (ddcfmtDNA), addressing the crucial challenge of BKPyVAN diagnosis. Urinary samples were collected at the time of biopsy from a total of 60 kidney transplant recipients, comprising 12 with stable function, 22 with T cell-mediated rejection, and 21 with biopsy-proven BKPyVAN. Our findings reveal that the ddcfmtDNA-to-ddcfDNA ratio exhibits superior capability in distinguishing BKPyVAN from other conditions, with a cutoff value of 4.96% (area under curve = 0.933; sensitivity: 71.4%; and specificity: 97.1%). Notably, an elevation of ddcfmtDNA levels is associated with mitochondrial damage, as visualized through electron microscopy. These results underscore the promise of non-invasive monitoring for detecting subtle mitochondrial damage and its potential utility in BKPyVAN diagnosis. Further investigations are required to advance this field of research.
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spelling doaj.art-a5838718837e4d9887ac2ab8bc3d5cb02024-03-27T13:28:01ZengMDPI AGBiomolecules2218-273X2024-03-0114334810.3390/biom14030348Cell-Free Mitochondrial DNA: An Upcoming Non-Invasive Tool for Diagnosis of BK Polyomavirus-Associated NephropathyLuying Guo0Sulin Luo1Xingxia Wang2Nengbo Zhang3Yamei Cheng4Jia Shen5Jianghua Chen6Rending Wang7Kidney Disease Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, ChinaKidney Disease Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, ChinaKidney Disease Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, ChinaKidney Disease Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, ChinaKidney Disease Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, ChinaKidney Disease Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, ChinaKidney Disease Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, ChinaKidney Disease Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, ChinaMitochondria are essential organelles that possess their own DNA. Mitochondrial dysfunction has been revealed in many kidney diseases, including BK polyomavirus-associated nephropathy (BKPyVAN). In this study, we introduce an innovative approach for non-invasive monitoring of mitochondrial impairment through urinary donor-derived cell-free mitochondrial DNA (ddcfmtDNA), addressing the crucial challenge of BKPyVAN diagnosis. Urinary samples were collected at the time of biopsy from a total of 60 kidney transplant recipients, comprising 12 with stable function, 22 with T cell-mediated rejection, and 21 with biopsy-proven BKPyVAN. Our findings reveal that the ddcfmtDNA-to-ddcfDNA ratio exhibits superior capability in distinguishing BKPyVAN from other conditions, with a cutoff value of 4.96% (area under curve = 0.933; sensitivity: 71.4%; and specificity: 97.1%). Notably, an elevation of ddcfmtDNA levels is associated with mitochondrial damage, as visualized through electron microscopy. These results underscore the promise of non-invasive monitoring for detecting subtle mitochondrial damage and its potential utility in BKPyVAN diagnosis. Further investigations are required to advance this field of research.https://www.mdpi.com/2218-273X/14/3/348BK polyomavirus-associated nephropathymitochondrial damagecell-free mitochondria DNA
spellingShingle Luying Guo
Sulin Luo
Xingxia Wang
Nengbo Zhang
Yamei Cheng
Jia Shen
Jianghua Chen
Rending Wang
Cell-Free Mitochondrial DNA: An Upcoming Non-Invasive Tool for Diagnosis of BK Polyomavirus-Associated Nephropathy
Biomolecules
BK polyomavirus-associated nephropathy
mitochondrial damage
cell-free mitochondria DNA
title Cell-Free Mitochondrial DNA: An Upcoming Non-Invasive Tool for Diagnosis of BK Polyomavirus-Associated Nephropathy
title_full Cell-Free Mitochondrial DNA: An Upcoming Non-Invasive Tool for Diagnosis of BK Polyomavirus-Associated Nephropathy
title_fullStr Cell-Free Mitochondrial DNA: An Upcoming Non-Invasive Tool for Diagnosis of BK Polyomavirus-Associated Nephropathy
title_full_unstemmed Cell-Free Mitochondrial DNA: An Upcoming Non-Invasive Tool for Diagnosis of BK Polyomavirus-Associated Nephropathy
title_short Cell-Free Mitochondrial DNA: An Upcoming Non-Invasive Tool for Diagnosis of BK Polyomavirus-Associated Nephropathy
title_sort cell free mitochondrial dna an upcoming non invasive tool for diagnosis of bk polyomavirus associated nephropathy
topic BK polyomavirus-associated nephropathy
mitochondrial damage
cell-free mitochondria DNA
url https://www.mdpi.com/2218-273X/14/3/348
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