Using Both Plasma and Urine Donor-Derived Cell-Free DNA to Identify Various Renal Allograft Injuries

Using Both Plasma and Urine Donor-Derived Cell-Free DNA to Identify Various Renal Allograft Injuries

Abstract Background This study was designed to investigate the association between donor-derived cell-free DNA (dd-cfDNA) and renal allograft injuries. Methods This single-center study enrolled 113 adult kidney transplant recipients with kidney biopsies. Plasma and urine dd-cfDNA was detected by tar...

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Veröffentlicht in:Clinical chemistry (Baltimore, Md.) Md.), 2022-06, Vol.68 (6), p.814-825
Hauptverfasser: Chen, Xu-Tao, Qiu, Jiang, Wu, Zi-Xuan, Zhang, Hui, Chen, Tong, Yang, Shi-Cong, Zhao, Guo-Dong, He, Yu, Shen, Xue, Luo, Jin-Quan, Huang, Yang, Wang, Chang-Xi, Chen, Li-Zhong, Wu, Cheng-Lin, Huang, Gang
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container_title Clinical chemistry (Baltimore, Md.)
container_volume 68
creator Chen, Xu-Tao
Qiu, Jiang
Wu, Zi-Xuan
Zhang, Hui
Chen, Tong
Yang, Shi-Cong
Zhao, Guo-Dong
He, Yu
Shen, Xue
Luo, Jin-Quan
Huang, Yang
Wang, Chang-Xi
Chen, Li-Zhong
Wu, Cheng-Lin
Huang, Gang
description Abstract Background This study was designed to investigate the association between donor-derived cell-free DNA (dd-cfDNA) and renal allograft injuries. Methods This single-center study enrolled 113 adult kidney transplant recipients with kidney biopsies. Plasma and urine dd-cfDNA was detected by target region capture sequencing. Results Plasma dd-cfDNA fraction was increased in multiple types of injuries, but most significantly in antibody-mediated rejection. Plasma dd-cfDNA fraction in isolated antibody-mediated rejection (1.94%, IQR: 1.15%, 2.33%) was higher than in T cell-mediated rejection (0.55%, IQR: 0.50%, 0.73%, P = 0.002) and negative biopsies (0.58%, IQR: 0.42%, 0.78%, P 
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Methods This single-center study enrolled 113 adult kidney transplant recipients with kidney biopsies. Plasma and urine dd-cfDNA was detected by target region capture sequencing. Results Plasma dd-cfDNA fraction was increased in multiple types of injuries, but most significantly in antibody-mediated rejection. Plasma dd-cfDNA fraction in isolated antibody-mediated rejection (1.94%, IQR: 1.15%, 2.33%) was higher than in T cell-mediated rejection (0.55%, IQR: 0.50%, 0.73%, P = 0.002) and negative biopsies (0.58%, IQR: 0.42%, 0.78%, P &lt; 0.001), but lower than in mixed rejection (2.49%, IQR: 1.16%, 4.90%, P = 0.342). Increased urine dd-cfDNA concentration was associated with several types of injury, but most significantly with BK polyomavirus-associated nephropathy. Urine dd-cfDNA concentration in BK polyomavirus-associated nephropathy (12.22 ng/mL, IQR: 6.53 ng/mL, 31.66 ng/mL) was respectively higher than that in T cell-mediated rejection (5.24 ng/mL, IQR: 3.22 ng/mL, 6.99 ng/mL, P = 0.001), borderline change (3.93 ng/mL, IQR: 2.45 ng/mL, 6.30 ng/mL, P &lt; 0.001), and negative biopsies (3.09 ng/mL, IQR: 1.94 ng/mL, 5.05 ng/mL, P &lt; 0.001). Plasma dd-cfDNA fraction was positively associated with glomerulitis (r = 0.365, P &lt; 0.001) and peri-tubular capillaritis (r = 0.344, P &lt; 0.001), while urine dd-cfDNA concentration correlated with tubulitis (r = 0.302, P = 0.002). Conclusions Both plasma and urine dd-cfDNA are sensitive markers for renal allograft injuries. The interpretation of a specific disease by dd-cfDNA should be combined with other clinical indicators.</description><identifier>ISSN: 0009-9147</identifier><identifier>EISSN: 1530-8561</identifier><identifier>DOI: 10.1093/clinchem/hvac053</identifier><identifier>PMID: 35587713</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><ispartof>Clinical chemistry (Baltimore, Md.), 2022-06, Vol.68 (6), p.814-825</ispartof><rights>American Association for Clinical Chemistry 2022. 2022</rights><rights>American Association for Clinical Chemistry 2022.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c377t-8ecd79a6acd524b5fb73fa43e2a35286d7a4653929fc02c18460fd61127a769a3</citedby><cites>FETCH-LOGICAL-c377t-8ecd79a6acd524b5fb73fa43e2a35286d7a4653929fc02c18460fd61127a769a3</cites><orcidid>0000-0001-8111-6694 ; 0000-0001-7433-3447</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35587713$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Xu-Tao</creatorcontrib><creatorcontrib>Qiu, Jiang</creatorcontrib><creatorcontrib>Wu, Zi-Xuan</creatorcontrib><creatorcontrib>Zhang, Hui</creatorcontrib><creatorcontrib>Chen, Tong</creatorcontrib><creatorcontrib>Yang, Shi-Cong</creatorcontrib><creatorcontrib>Zhao, Guo-Dong</creatorcontrib><creatorcontrib>He, Yu</creatorcontrib><creatorcontrib>Shen, Xue</creatorcontrib><creatorcontrib>Luo, Jin-Quan</creatorcontrib><creatorcontrib>Huang, Yang</creatorcontrib><creatorcontrib>Wang, Chang-Xi</creatorcontrib><creatorcontrib>Chen, Li-Zhong</creatorcontrib><creatorcontrib>Wu, Cheng-Lin</creatorcontrib><creatorcontrib>Huang, Gang</creatorcontrib><title>Using Both Plasma and Urine Donor-Derived Cell-Free DNA to Identify Various Renal Allograft Injuries</title><title>Clinical chemistry (Baltimore, Md.)</title><addtitle>Clin Chem</addtitle><description>Abstract Background This study was designed to investigate the association between donor-derived cell-free DNA (dd-cfDNA) and renal allograft injuries. Methods This single-center study enrolled 113 adult kidney transplant recipients with kidney biopsies. Plasma and urine dd-cfDNA was detected by target region capture sequencing. Results Plasma dd-cfDNA fraction was increased in multiple types of injuries, but most significantly in antibody-mediated rejection. Plasma dd-cfDNA fraction in isolated antibody-mediated rejection (1.94%, IQR: 1.15%, 2.33%) was higher than in T cell-mediated rejection (0.55%, IQR: 0.50%, 0.73%, P = 0.002) and negative biopsies (0.58%, IQR: 0.42%, 0.78%, P &lt; 0.001), but lower than in mixed rejection (2.49%, IQR: 1.16%, 4.90%, P = 0.342). Increased urine dd-cfDNA concentration was associated with several types of injury, but most significantly with BK polyomavirus-associated nephropathy. Urine dd-cfDNA concentration in BK polyomavirus-associated nephropathy (12.22 ng/mL, IQR: 6.53 ng/mL, 31.66 ng/mL) was respectively higher than that in T cell-mediated rejection (5.24 ng/mL, IQR: 3.22 ng/mL, 6.99 ng/mL, P = 0.001), borderline change (3.93 ng/mL, IQR: 2.45 ng/mL, 6.30 ng/mL, P &lt; 0.001), and negative biopsies (3.09 ng/mL, IQR: 1.94 ng/mL, 5.05 ng/mL, P &lt; 0.001). Plasma dd-cfDNA fraction was positively associated with glomerulitis (r = 0.365, P &lt; 0.001) and peri-tubular capillaritis (r = 0.344, P &lt; 0.001), while urine dd-cfDNA concentration correlated with tubulitis (r = 0.302, P = 0.002). Conclusions Both plasma and urine dd-cfDNA are sensitive markers for renal allograft injuries. The interpretation of a specific disease by dd-cfDNA should be combined with other clinical indicators.</description><issn>0009-9147</issn><issn>1530-8561</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><recordid>eNqFkMFLwzAUh4MoOqd3T5KjINWkaZL2ODeng6Eizmt5S1IXaZOZtIP991Y2vXp6vMf3-_H4ELqg5IaSgt2q2jq1Ms3tagOKcHaABpQzkuRc0EM0IIQUSUEzeYJOY_zs10zm4hidMM5zKSkbIL2I1n3gO9-u8EsNsQEMTuNFsM7giXc-JBMT7MZoPDZ1nUyD6e9PI9x6PNPGtbba4ncI1ncRvxoHNR7Vtf8IULV45j67YE08Q0cV1NGc7-cQLab3b-PHZP78MBuP5oliUrZJbpSWBQhQmqfZkldLySrImEmB8TQXWkImOCvSolIkVTTPBKm0oDSVIEUBbIiudr3r4L86E9uysVH1b4Mz_X9lKoSUOSe57FGyQ1XwMQZTletgGwjbkpLyx23567bcu-0jl_v2btkY_Rf4ldkD1zvAd-v_674BnK-Ghw</recordid><startdate>20220601</startdate><enddate>20220601</enddate><creator>Chen, Xu-Tao</creator><creator>Qiu, Jiang</creator><creator>Wu, Zi-Xuan</creator><creator>Zhang, Hui</creator><creator>Chen, Tong</creator><creator>Yang, Shi-Cong</creator><creator>Zhao, Guo-Dong</creator><creator>He, Yu</creator><creator>Shen, Xue</creator><creator>Luo, Jin-Quan</creator><creator>Huang, Yang</creator><creator>Wang, Chang-Xi</creator><creator>Chen, Li-Zhong</creator><creator>Wu, Cheng-Lin</creator><creator>Huang, Gang</creator><general>Oxford University Press</general><scope>TOX</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8111-6694</orcidid><orcidid>https://orcid.org/0000-0001-7433-3447</orcidid></search><sort><creationdate>20220601</creationdate><title>Using Both Plasma and Urine Donor-Derived Cell-Free DNA to Identify Various Renal Allograft Injuries</title><author>Chen, Xu-Tao ; Qiu, Jiang ; Wu, Zi-Xuan ; Zhang, Hui ; Chen, Tong ; Yang, Shi-Cong ; Zhao, Guo-Dong ; He, Yu ; Shen, Xue ; Luo, Jin-Quan ; Huang, Yang ; Wang, Chang-Xi ; Chen, Li-Zhong ; Wu, Cheng-Lin ; Huang, Gang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c377t-8ecd79a6acd524b5fb73fa43e2a35286d7a4653929fc02c18460fd61127a769a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Xu-Tao</creatorcontrib><creatorcontrib>Qiu, Jiang</creatorcontrib><creatorcontrib>Wu, Zi-Xuan</creatorcontrib><creatorcontrib>Zhang, Hui</creatorcontrib><creatorcontrib>Chen, Tong</creatorcontrib><creatorcontrib>Yang, Shi-Cong</creatorcontrib><creatorcontrib>Zhao, Guo-Dong</creatorcontrib><creatorcontrib>He, Yu</creatorcontrib><creatorcontrib>Shen, Xue</creatorcontrib><creatorcontrib>Luo, Jin-Quan</creatorcontrib><creatorcontrib>Huang, Yang</creatorcontrib><creatorcontrib>Wang, Chang-Xi</creatorcontrib><creatorcontrib>Chen, Li-Zhong</creatorcontrib><creatorcontrib>Wu, Cheng-Lin</creatorcontrib><creatorcontrib>Huang, Gang</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical chemistry (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Xu-Tao</au><au>Qiu, Jiang</au><au>Wu, Zi-Xuan</au><au>Zhang, Hui</au><au>Chen, Tong</au><au>Yang, Shi-Cong</au><au>Zhao, Guo-Dong</au><au>He, Yu</au><au>Shen, Xue</au><au>Luo, Jin-Quan</au><au>Huang, Yang</au><au>Wang, Chang-Xi</au><au>Chen, Li-Zhong</au><au>Wu, Cheng-Lin</au><au>Huang, Gang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Using Both Plasma and Urine Donor-Derived Cell-Free DNA to Identify Various Renal Allograft Injuries</atitle><jtitle>Clinical chemistry (Baltimore, Md.)</jtitle><addtitle>Clin Chem</addtitle><date>2022-06-01</date><risdate>2022</risdate><volume>68</volume><issue>6</issue><spage>814</spage><epage>825</epage><pages>814-825</pages><issn>0009-9147</issn><eissn>1530-8561</eissn><abstract>Abstract Background This study was designed to investigate the association between donor-derived cell-free DNA (dd-cfDNA) and renal allograft injuries. Methods This single-center study enrolled 113 adult kidney transplant recipients with kidney biopsies. Plasma and urine dd-cfDNA was detected by target region capture sequencing. Results Plasma dd-cfDNA fraction was increased in multiple types of injuries, but most significantly in antibody-mediated rejection. Plasma dd-cfDNA fraction in isolated antibody-mediated rejection (1.94%, IQR: 1.15%, 2.33%) was higher than in T cell-mediated rejection (0.55%, IQR: 0.50%, 0.73%, P = 0.002) and negative biopsies (0.58%, IQR: 0.42%, 0.78%, P &lt; 0.001), but lower than in mixed rejection (2.49%, IQR: 1.16%, 4.90%, P = 0.342). Increased urine dd-cfDNA concentration was associated with several types of injury, but most significantly with BK polyomavirus-associated nephropathy. Urine dd-cfDNA concentration in BK polyomavirus-associated nephropathy (12.22 ng/mL, IQR: 6.53 ng/mL, 31.66 ng/mL) was respectively higher than that in T cell-mediated rejection (5.24 ng/mL, IQR: 3.22 ng/mL, 6.99 ng/mL, P = 0.001), borderline change (3.93 ng/mL, IQR: 2.45 ng/mL, 6.30 ng/mL, P &lt; 0.001), and negative biopsies (3.09 ng/mL, IQR: 1.94 ng/mL, 5.05 ng/mL, P &lt; 0.001). Plasma dd-cfDNA fraction was positively associated with glomerulitis (r = 0.365, P &lt; 0.001) and peri-tubular capillaritis (r = 0.344, P &lt; 0.001), while urine dd-cfDNA concentration correlated with tubulitis (r = 0.302, P = 0.002). Conclusions Both plasma and urine dd-cfDNA are sensitive markers for renal allograft injuries. The interpretation of a specific disease by dd-cfDNA should be combined with other clinical indicators.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>35587713</pmid><doi>10.1093/clinchem/hvac053</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-8111-6694</orcidid><orcidid>https://orcid.org/0000-0001-7433-3447</orcidid><oa>free_for_read</oa></addata></record>
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title Using Both Plasma and Urine Donor-Derived Cell-Free DNA to Identify Various Renal Allograft Injuries
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