Urinary Metabolomics for Noninvasive Detection of Borderline and Acute T Cell–Mediated Rejection in Children After Kidney Transplantation
The goal of this study was to evaluate the utility of urinary metabolomics for noninvasive diagnosis of T cell–mediated rejection (TCMR) in pediatric kidney transplant recipients. Urine samples (n = 277) from 57 patients with surveillance or indication kidney biopsies were assayed for 134 unique met...
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| Veröffentlicht in: | American journal of transplantation 2014-10, Vol.14 (10), p.2339-2349 |
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| creator | Blydt‐Hansen, T. D. Sharma, A. Gibson, I. W. Mandal, R. Wishart, D. S. |
| description | The goal of this study was to evaluate the utility of urinary metabolomics for noninvasive diagnosis of T cell–mediated rejection (TCMR) in pediatric kidney transplant recipients. Urine samples (n = 277) from 57 patients with surveillance or indication kidney biopsies were assayed for 134 unique metabolites by quantitative mass spectrometry. Samples without TCMR (n = 183) were compared to borderline tubulitis (n = 54) and TCMR (n = 30). Partial least squares discriminant analysis identified distinct classifiers for TCMR (area under receiver operating characteristic curve [AUC] = 0.892; 95% confidence interval [CI] 0.827–0.957) and borderline tubulitis (AUC = 0.836; 95% CI 0.781–0.892), respectively. Application of the TCMR classifier to borderline tubulitis samples yielded a discriminant score (−0.47 ± 0.33) mid‐way between TCMR (−0.20 ± 0.34) and No TCMR (−0.80 ± 0.32) (p |
| doi_str_mv | 10.1111/ajt.12837 |
| format | Article |
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This study identifies patterns of urinary metabolites associated with the presence and severity of T cell‐mediated rejection, highlighting the potential utility of urinary metabolomics for noninvasive monitoring.</description><identifier>ISSN: 1600-6135</identifier><identifier>EISSN: 1600-6143</identifier><identifier>DOI: 10.1111/ajt.12837</identifier><identifier>PMID: 25138024</identifier><language>eng</language><publisher>Hoboken, NJ: Wiley</publisher><subject>Adolescent ; Biological and medical sciences ; Biomarker ; Child ; clinical research ; Female ; General aspects ; Graft Rejection - immunology ; Humans ; Kidney Transplantation ; Male ; Mass Spectrometry ; Medical sciences ; Metabolomics ; nephrology ; pediatrics ; practice ; protocol biopsy ; rejection: acute ; rejection: T cell–mediated (TCMR) ; science ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Surgery of the urinary system ; T-Lymphocytes - immunology ; translational research ; Urine</subject><ispartof>American journal of transplantation, 2014-10, Vol.14 (10), p.2339-2349</ispartof><rights>Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons</rights><rights>2015 INIST-CNRS</rights><rights>Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4887-3c3ea04356431759a39ad6874676c8f33f9b019602aebf3deed78690d6d22a733</citedby><cites>FETCH-LOGICAL-c4887-3c3ea04356431759a39ad6874676c8f33f9b019602aebf3deed78690d6d22a733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fajt.12837$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fajt.12837$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28945656$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25138024$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Blydt‐Hansen, T. D.</creatorcontrib><creatorcontrib>Sharma, A.</creatorcontrib><creatorcontrib>Gibson, I. W.</creatorcontrib><creatorcontrib>Mandal, R.</creatorcontrib><creatorcontrib>Wishart, D. S.</creatorcontrib><title>Urinary Metabolomics for Noninvasive Detection of Borderline and Acute T Cell–Mediated Rejection in Children After Kidney Transplantation</title><title>American journal of transplantation</title><addtitle>Am J Transplant</addtitle><description>The goal of this study was to evaluate the utility of urinary metabolomics for noninvasive diagnosis of T cell–mediated rejection (TCMR) in pediatric kidney transplant recipients. Urine samples (n = 277) from 57 patients with surveillance or indication kidney biopsies were assayed for 134 unique metabolites by quantitative mass spectrometry. Samples without TCMR (n = 183) were compared to borderline tubulitis (n = 54) and TCMR (n = 30). Partial least squares discriminant analysis identified distinct classifiers for TCMR (area under receiver operating characteristic curve [AUC] = 0.892; 95% confidence interval [CI] 0.827–0.957) and borderline tubulitis (AUC = 0.836; 95% CI 0.781–0.892), respectively. Application of the TCMR classifier to borderline tubulitis samples yielded a discriminant score (−0.47 ± 0.33) mid‐way between TCMR (−0.20 ± 0.34) and No TCMR (−0.80 ± 0.32) (p < 0.001 for all comparisons). Discriminant scoring for combined borderline/TCMR versus No TCMR (AUC = 0.900; 95% CI 0.859–0.940) applied to a validation cohort robustly distinguished between samples with (−0.08 ± 0.52) and without (−0.65 ± 0.54, p < 0.001) borderline/TCMR (p < 0.001). The TCMR discriminant score was driven by histological t‐score, ct‐score, donor‐specific antibody and biopsy indication, and was unaffected by renal function, interstitial or microcirculatory inflammation, interstitial fibrosis or pyuria. These preliminary findings suggest that urinary metabolomics is a sensitive, specific and noninvasive tool for TCMR identification that is superior to serum creatinine, with minimal confounding by other allograft injury processes.
This study identifies patterns of urinary metabolites associated with the presence and severity of T cell‐mediated rejection, highlighting the potential utility of urinary metabolomics for noninvasive monitoring.</description><subject>Adolescent</subject><subject>Biological and medical sciences</subject><subject>Biomarker</subject><subject>Child</subject><subject>clinical research</subject><subject>Female</subject><subject>General aspects</subject><subject>Graft Rejection - immunology</subject><subject>Humans</subject><subject>Kidney Transplantation</subject><subject>Male</subject><subject>Mass Spectrometry</subject><subject>Medical sciences</subject><subject>Metabolomics</subject><subject>nephrology</subject><subject>pediatrics</subject><subject>practice</subject><subject>protocol biopsy</subject><subject>rejection: acute</subject><subject>rejection: T cell–mediated (TCMR)</subject><subject>science</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the urinary system</subject><subject>T-Lymphocytes - immunology</subject><subject>translational research</subject><subject>Urine</subject><issn>1600-6135</issn><issn>1600-6143</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10c1uEzEQB3ALgWgbOPACyBJCKoe0_ti1vccQvmlBQul55dizwpFjp7a3KDfuHHlDngSnCUVCwpfx4efxaP4IPaHkjNZzrlfljDLF5T10TAUhU0Ebfv_uztsjdJLzihAqmWIP0RFrKVeENcfox1VyQactvoSil9HHtTMZDzHhTzG4cKOzuwH8CgqY4mLAccAvY7KQvAuAdbB4ZsYCeIHn4P2v7z8vwTpdwOIvsDq8cQHPvzpvEwQ8Gwok_NHZAFu8SDrkjdeh6B18hB4M2md4fKgTdPXm9WL-bnrx-e37-exiahql5JQbDpo0vBUNp7LtNO-0FUo2QgqjBs6HbkloJwjTsBy4BbBSiY5YYRnTkvMJOt333aR4PUIu_dplU8fXAeKYe9oK3ilGapmgZ__QVRxTqNPtFGsawSWp6sVemRRzTjD0m-TWdas9Jf0uob4m1N8mVO3TQ8dxuQZ7J_9EUsHzA9DZaD_UHRmX_zrVNa24He187745D9v__9jPPiz2X_8GeteoXw</recordid><startdate>201410</startdate><enddate>201410</enddate><creator>Blydt‐Hansen, T. D.</creator><creator>Sharma, A.</creator><creator>Gibson, I. W.</creator><creator>Mandal, R.</creator><creator>Wishart, D. S.</creator><general>Wiley</general><general>Elsevier Limited</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201410</creationdate><title>Urinary Metabolomics for Noninvasive Detection of Borderline and Acute T Cell–Mediated Rejection in Children After Kidney Transplantation</title><author>Blydt‐Hansen, T. D. ; Sharma, A. ; Gibson, I. W. ; Mandal, R. ; Wishart, D. S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4887-3c3ea04356431759a39ad6874676c8f33f9b019602aebf3deed78690d6d22a733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adolescent</topic><topic>Biological and medical sciences</topic><topic>Biomarker</topic><topic>Child</topic><topic>clinical research</topic><topic>Female</topic><topic>General aspects</topic><topic>Graft Rejection - immunology</topic><topic>Humans</topic><topic>Kidney Transplantation</topic><topic>Male</topic><topic>Mass Spectrometry</topic><topic>Medical sciences</topic><topic>Metabolomics</topic><topic>nephrology</topic><topic>pediatrics</topic><topic>practice</topic><topic>protocol biopsy</topic><topic>rejection: acute</topic><topic>rejection: T cell–mediated (TCMR)</topic><topic>science</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Surgery of the urinary system</topic><topic>T-Lymphocytes - immunology</topic><topic>translational research</topic><topic>Urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Blydt‐Hansen, T. D.</creatorcontrib><creatorcontrib>Sharma, A.</creatorcontrib><creatorcontrib>Gibson, I. W.</creatorcontrib><creatorcontrib>Mandal, R.</creatorcontrib><creatorcontrib>Wishart, D. 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S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Urinary Metabolomics for Noninvasive Detection of Borderline and Acute T Cell–Mediated Rejection in Children After Kidney Transplantation</atitle><jtitle>American journal of transplantation</jtitle><addtitle>Am J Transplant</addtitle><date>2014-10</date><risdate>2014</risdate><volume>14</volume><issue>10</issue><spage>2339</spage><epage>2349</epage><pages>2339-2349</pages><issn>1600-6135</issn><eissn>1600-6143</eissn><abstract>The goal of this study was to evaluate the utility of urinary metabolomics for noninvasive diagnosis of T cell–mediated rejection (TCMR) in pediatric kidney transplant recipients. Urine samples (n = 277) from 57 patients with surveillance or indication kidney biopsies were assayed for 134 unique metabolites by quantitative mass spectrometry. Samples without TCMR (n = 183) were compared to borderline tubulitis (n = 54) and TCMR (n = 30). Partial least squares discriminant analysis identified distinct classifiers for TCMR (area under receiver operating characteristic curve [AUC] = 0.892; 95% confidence interval [CI] 0.827–0.957) and borderline tubulitis (AUC = 0.836; 95% CI 0.781–0.892), respectively. Application of the TCMR classifier to borderline tubulitis samples yielded a discriminant score (−0.47 ± 0.33) mid‐way between TCMR (−0.20 ± 0.34) and No TCMR (−0.80 ± 0.32) (p < 0.001 for all comparisons). Discriminant scoring for combined borderline/TCMR versus No TCMR (AUC = 0.900; 95% CI 0.859–0.940) applied to a validation cohort robustly distinguished between samples with (−0.08 ± 0.52) and without (−0.65 ± 0.54, p < 0.001) borderline/TCMR (p < 0.001). The TCMR discriminant score was driven by histological t‐score, ct‐score, donor‐specific antibody and biopsy indication, and was unaffected by renal function, interstitial or microcirculatory inflammation, interstitial fibrosis or pyuria. These preliminary findings suggest that urinary metabolomics is a sensitive, specific and noninvasive tool for TCMR identification that is superior to serum creatinine, with minimal confounding by other allograft injury processes.
This study identifies patterns of urinary metabolites associated with the presence and severity of T cell‐mediated rejection, highlighting the potential utility of urinary metabolomics for noninvasive monitoring.</abstract><cop>Hoboken, NJ</cop><pub>Wiley</pub><pmid>25138024</pmid><doi>10.1111/ajt.12837</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Biological and medical sciences Biomarker Child clinical research Female General aspects Graft Rejection - immunology Humans Kidney Transplantation Male Mass Spectrometry Medical sciences Metabolomics nephrology pediatrics practice protocol biopsy rejection: acute rejection: T cell–mediated (TCMR) science Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the urinary system T-Lymphocytes - immunology translational research Urine |
| title | Urinary Metabolomics for Noninvasive Detection of Borderline and Acute T Cell–Mediated Rejection in Children After Kidney Transplantation |
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