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On-line Access: 2021-11-16

Received: 2021-02-16

Revision Accepted: 2021-06-28

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 ORCID:

Rending WANG

https://orcid.org/0000-0002-2063-8533

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Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.11 P.917-928

http://doi.org/10.1631/jzus.B2100131


Urinary donor-derived cell-free DNA as a non-invasive biomarker for BK polyomavirus-associated nephropathy


Author(s):  Jia SHEN, Luying GUO, Wenhua LEI, Shuaihui LIU, Pengpeng YAN, Haitao LIU, Jingyi ZHOU, Qin ZHOU, Feng LIU, Tingya JIANG, Huiping WANG, Jianyong WU, Jianghua CHEN, Rending WANG

Affiliation(s):  Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; more

Corresponding email(s):   rd_wangjia@zju.edu.cn

Key Words:  Donor-derived cell-free DNA (ddcfDNA), BK polyomavirus-associated nephropathy (BKPyVAN), T cell-mediated rejection (TCMR), Urine, Differential diagnosis


Jia SHEN, Luying GUO, Wenhua LEI, Shuaihui LIU, Pengpeng YAN, Haitao LIU, Jingyi ZHOU, Qin ZHOU, Feng LIU, Tingya JIANG, Huiping WANG, Jianyong WU, Jianghua CHEN, Rending WANG. Urinary donor-derived cell-free DNA as a non-invasive biomarker for BK polyomavirus-associated nephropathy[J]. Journal of Zhejiang University Science B, 2021, 22(11): 917-928.

@article{title="Urinary donor-derived cell-free DNA as a non-invasive biomarker for BK polyomavirus-associated nephropathy",
author="Jia SHEN, Luying GUO, Wenhua LEI, Shuaihui LIU, Pengpeng YAN, Haitao LIU, Jingyi ZHOU, Qin ZHOU, Feng LIU, Tingya JIANG, Huiping WANG, Jianyong WU, Jianghua CHEN, Rending WANG",
journal="Journal of Zhejiang University Science B",
volume="22",
number="11",
pages="917-928",
year="2021",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2100131"
}

%0 Journal Article
%T Urinary donor-derived cell-free DNA as a non-invasive biomarker for BK polyomavirus-associated nephropathy
%A Jia SHEN
%A Luying GUO
%A Wenhua LEI
%A Shuaihui LIU
%A Pengpeng YAN
%A Haitao LIU
%A Jingyi ZHOU
%A Qin ZHOU
%A Feng LIU
%A Tingya JIANG
%A Huiping WANG
%A Jianyong WU
%A Jianghua CHEN
%A Rending WANG
%J Journal of Zhejiang University SCIENCE B
%V 22
%N 11
%P 917-928
%@ 1673-1581
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2100131

TY - JOUR
T1 - Urinary donor-derived cell-free DNA as a non-invasive biomarker for BK polyomavirus-associated nephropathy
A1 - Jia SHEN
A1 - Luying GUO
A1 - Wenhua LEI
A1 - Shuaihui LIU
A1 - Pengpeng YAN
A1 - Haitao LIU
A1 - Jingyi ZHOU
A1 - Qin ZHOU
A1 - Feng LIU
A1 - Tingya JIANG
A1 - Huiping WANG
A1 - Jianyong WU
A1 - Jianghua CHEN
A1 - Rending WANG
J0 - Journal of Zhejiang University Science B
VL - 22
IS - 11
SP - 917
EP - 928
%@ 1673-1581
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2100131


Abstract: 
BK polyomavirus-associated nephropathy (BKPyVAN) is a common cause of allograft failure. However, differentiation between BKPyVAN and type I t cell-mediated rejection (TCMR) is challenging when simian virus 40 (SV40) staining is negative, because of the similarities in histopathology. This study investigated whether donor-derived cell-free DNA (ddcfDNA) can be used to differentiate BKPyVAN. Target region capture sequencing was applied to detect the ddcfDNAs of 12 recipients with stable graft function, 22 with type I TCMR, 21 with proven BKPyVAN, and 5 with possible PyVAN. We found that urinary ddcfDNA levels were upregulated in recipients with graft injury, whereas plasma ddcfDNA levels were comparable for all groups. The median urinary concentrations and fractions of ddcfDNA in proven BKPyVAN recipients were significantly higher than those in type I TCMR recipients (10.4 vs. 6.1 ng/mL, P<0.001 and 68.4% vs. 55.3%, P=0.013, respectively). Urinary ddcfDNA fractions (not concentrations) were higher in the BKPyVAN-pure subgroup than in the BKPyVAN-rejection-like subgroup (81.30% vs. 56.64%, P=0.025). With a cut-off value of 7.81 ng/mL, urinary ddcfDNA concentrations distinguished proven BKPyVAN from type I TCMR (area under the curve (AUC)=0.848, 95% confidence interval (95% CI): 0.734 to 0.963). These findings suggest that urinary ddcfDNA is a non-invasive biomarker which can reliably differentiate BKPyVAN from type I TCMR.

尿液供体来源的细胞游离DNA是BK病毒相关肾病的生物标志物

目的:BK病毒相关肾病(BKPyVAN)是移植肾丢失的常见原因之一。然而,由于BKPyVAN和I型T细胞介导的排斥反应(TCMR)具有相似的病理表现,因此在猿猴空泡病毒40(SV40)染色阴性时,病理鉴别两者具有难度。
创新点:本文首次研究了供体来源的细胞游离DNA(ddcfDNA)能否区分BKPyVAN和I型TCMR。
方法:采用目标区域杂交捕获测序检测法,对12例肾功能稳定、22例I型TCMR、21例病理证实BKPyVAN和5例疑似PyVAN患者的ddcfDNA进行检测。
结论:在有移植物损伤时,患者尿液中ddcfDNA水平增加,而血浆中ddcfDNA无明显改变。病理证实BKPyVAN组尿液ddcfDNA的浓度和百分比的中位数均明显高于I型TCMR组(10.4 vs. 6.1 ng/mL,P<0.001;68.4% vs. 55.3%,P=0.013)。在单纯BKPyVAN亚组中,尿液ddcfDNA的百分比较BKPyVAN排斥样改变组升高明显(81.30% vs. 56.64%,P=0.025),而ddcfDNA的浓度则无明显升高。尿液ddcfDNA浓度7.81 ng/mL可作为区分病理证实BKPyVAN和I型TCMR的阈值(AUC=0.848,95%置信区间:0.734-0.963)。

关键词:供体来源细胞游离DNA;BK病毒相关肾病;T细胞介导的排斥反应;尿液;鉴别诊断

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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