Rates and Determinants of Progression to Graft Failure in Kidney Allograft Recipients With De Novo Donor‐Specific Antibody
Understanding rates and determinants of clinical pathologic progression for recipients with de novo donor‐specific antibody (dnDSA), especially subclinical dnDSA, may identify surrogate endpoints and inform clinical trial design. A consecutive cohort of 508 renal transplant recipients (n = 64 with d...
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| Veröffentlicht in: | American journal of transplantation 2015-11, Vol.15 (11), p.2921-2930 |
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| creator | Wiebe, C. Gibson, I. W. Blydt‐Hansen, T. D. Pochinco, D. Birk, P. E. Ho, J. Karpinski, M. Goldberg, A. Storsley, L. Rush, D. N. Nickerson, P. W. |
| description | Understanding rates and determinants of clinical pathologic progression for recipients with de novo donor‐specific antibody (dnDSA), especially subclinical dnDSA, may identify surrogate endpoints and inform clinical trial design. A consecutive cohort of 508 renal transplant recipients (n = 64 with dnDSA) was studied. Recipients (n = 388) without dnDSA or dysfunction had an eGFR decline of −0.65 mL/min/1.73 m2/year. In recipients with dnDSA, the rate eGFR decline was significantly increased prior to dnDSA onset (−2.89 vs. −0.65 mL/min/1.73 m2/year, p |
| doi_str_mv | 10.1111/ajt.13347 |
| format | Article |
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In this study, the authors analyze clinical and histologic risk factors available at the time of de novo donor‐specific antibody detection to determine clinical and histologic predictors of subsequent allograft failure, and their importance for clinical trial design.</description><identifier>ISSN: 1600-6135</identifier><identifier>EISSN: 1600-6143</identifier><identifier>DOI: 10.1111/ajt.13347</identifier><identifier>PMID: 26096305</identifier><language>eng</language><publisher>United States: Elsevier Limited</publisher><subject>Acute Disease ; Adult ; Age Factors ; Alloantibody ; Allografts - immunology ; Child ; Child, Preschool ; Chronic Disease ; Clinical trials ; Cohort Studies ; compliance/adherence ; Delayed Graft Function - immunology ; Disease Progression ; Follow-Up Studies ; Graft Rejection - immunology ; Graft Rejection - pathology ; Health risk assessment ; Humans ; Isoantibodies - analysis ; Isoantibodies - immunology ; Kaplan-Meier Estimate ; Kidney Transplantation - adverse effects ; Kidney Transplantation - methods ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Proportional Hazards Models ; rejection: antibody‐mediated (ABMR) ; rejection: chronic ; rejection: T cell–mediated (TCMR) ; Retrospective Studies ; Risk Assessment ; Sex Factors ; Statistics, Nonparametric ; T-Lymphocytes, Regulatory - immunology ; Time Factors ; Transplant Recipients ; Treatment Outcome</subject><ispartof>American journal of transplantation, 2015-11, Vol.15 (11), p.2921-2930</ispartof><rights>Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons</rights><rights>Copyright 2015 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-c4587-21d3113e3e71ca032d44b2b2abfe539e5cf0cf494227c2b652a72d32a08488f93</citedby><cites>FETCH-LOGICAL-c4587-21d3113e3e71ca032d44b2b2abfe539e5cf0cf494227c2b652a72d32a08488f93</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.13347$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fajt.13347$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26096305$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wiebe, C.</creatorcontrib><creatorcontrib>Gibson, I. W.</creatorcontrib><creatorcontrib>Blydt‐Hansen, T. D.</creatorcontrib><creatorcontrib>Pochinco, D.</creatorcontrib><creatorcontrib>Birk, P. E.</creatorcontrib><creatorcontrib>Ho, J.</creatorcontrib><creatorcontrib>Karpinski, M.</creatorcontrib><creatorcontrib>Goldberg, A.</creatorcontrib><creatorcontrib>Storsley, L.</creatorcontrib><creatorcontrib>Rush, D. N.</creatorcontrib><creatorcontrib>Nickerson, P. W.</creatorcontrib><title>Rates and Determinants of Progression to Graft Failure in Kidney Allograft Recipients With De Novo Donor‐Specific Antibody</title><title>American journal of transplantation</title><addtitle>Am J Transplant</addtitle><description>Understanding rates and determinants of clinical pathologic progression for recipients with de novo donor‐specific antibody (dnDSA), especially subclinical dnDSA, may identify surrogate endpoints and inform clinical trial design. A consecutive cohort of 508 renal transplant recipients (n = 64 with dnDSA) was studied. Recipients (n = 388) without dnDSA or dysfunction had an eGFR decline of −0.65 mL/min/1.73 m2/year. In recipients with dnDSA, the rate eGFR decline was significantly increased prior to dnDSA onset (−2.89 vs. −0.65 mL/min/1.73 m2/year, p < 0.0001) and accelerated post‐dnDSA (−3.63 vs. −2.89 mL/min/1.73 m2/year, p < 0.0001), suggesting that dnDSA is both a marker and contributor to ongoing alloimmunity. Time to 50% post‐dnDSA graft loss was longer in recipients with subclinical versus a clinical dnDSA phenotype (8.3 vs. 3.3 years, p < 0.0001). Analysis of 1091 allograft biopsies found that dnDSA and time independently predicted chronic glomerulopathy (cg), but not interstitial fibrosis and tubular atrophy (IFTA). Early T cell–mediated rejection, nonadherence, and time were multivariate predictors of IFTA. Independent risk factors for post‐dnDSA graft survival available prior to, or at the time of, dnDSA detection were delayed graft function, nonadherence, dnDSA mean fluorescence intensity sum score, tubulitis, and cg. Ultimately, dnDSA is part of a continuum of mixed alloimmune‐mediated injury, which requires solutions targeting T and B cells.
In this study, the authors analyze clinical and histologic risk factors available at the time of de novo donor‐specific antibody detection to determine clinical and histologic predictors of subsequent allograft failure, and their importance for clinical trial design.</description><subject>Acute Disease</subject><subject>Adult</subject><subject>Age Factors</subject><subject>Alloantibody</subject><subject>Allografts - immunology</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Chronic Disease</subject><subject>Clinical trials</subject><subject>Cohort Studies</subject><subject>compliance/adherence</subject><subject>Delayed Graft Function - immunology</subject><subject>Disease Progression</subject><subject>Follow-Up Studies</subject><subject>Graft Rejection - immunology</subject><subject>Graft Rejection - pathology</subject><subject>Health risk assessment</subject><subject>Humans</subject><subject>Isoantibodies - analysis</subject><subject>Isoantibodies - immunology</subject><subject>Kaplan-Meier Estimate</subject><subject>Kidney Transplantation - adverse effects</subject><subject>Kidney Transplantation - methods</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Predictive Value of Tests</subject><subject>Proportional Hazards Models</subject><subject>rejection: antibody‐mediated (ABMR)</subject><subject>rejection: chronic</subject><subject>rejection: T cell–mediated (TCMR)</subject><subject>Retrospective Studies</subject><subject>Risk Assessment</subject><subject>Sex Factors</subject><subject>Statistics, Nonparametric</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>Time Factors</subject><subject>Transplant Recipients</subject><subject>Treatment Outcome</subject><issn>1600-6135</issn><issn>1600-6143</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10ctuEzEUBmALgUgaWPQFKktsYDGJb3PJMmpIuESAQhDLkcdzXBxN7NT2UEViwSPwjDwJDmmzQMIbW_LnX0f-EbqkZEzTmshtHFPORfkIDWlBSFZQwR-fzzwfoIsQtoTQklXsKRqwgkwLTvIh-rGWEQKWtsVziOB3xkobA3Yaf_LuxkMIxlkcHV56qSNeSNP1HrCx-L1pLRzwrOuSO96tQZm9gePzryZ-S4H4g_vu8NxZ53___PV5n4A2Cs9sNI1rD8_QEy27AM_v9xH6sni9uX6TrT4u317PVpkSeVVmjLacUg4cSqok4awVomENk42GnE8hV5ooLaaCsVKxpsiZLFnLmSSVqCo95SP08pS79-62hxDrnQkKuk5acH2o07fkOWOClIm--IduXe9tmu6oeMVZwXlSr05KeReCB13vvdlJf6gpqY-V1KmS-m8lyV7dJ_bNDtqzfOgggckJ3JkODv9PqmfvNqfIP99hla4</recordid><startdate>201511</startdate><enddate>201511</enddate><creator>Wiebe, C.</creator><creator>Gibson, I. W.</creator><creator>Blydt‐Hansen, T. D.</creator><creator>Pochinco, D.</creator><creator>Birk, P. E.</creator><creator>Ho, J.</creator><creator>Karpinski, M.</creator><creator>Goldberg, A.</creator><creator>Storsley, L.</creator><creator>Rush, D. N.</creator><creator>Nickerson, P. W.</creator><general>Elsevier Limited</general><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>201511</creationdate><title>Rates and Determinants of Progression to Graft Failure in Kidney Allograft Recipients With De Novo Donor‐Specific Antibody</title><author>Wiebe, C. ; Gibson, I. W. ; Blydt‐Hansen, T. D. ; Pochinco, D. ; Birk, P. E. ; Ho, J. ; Karpinski, M. ; Goldberg, A. ; Storsley, L. ; Rush, D. N. ; Nickerson, P. 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W.</creatorcontrib><creatorcontrib>Blydt‐Hansen, T. D.</creatorcontrib><creatorcontrib>Pochinco, D.</creatorcontrib><creatorcontrib>Birk, P. E.</creatorcontrib><creatorcontrib>Ho, J.</creatorcontrib><creatorcontrib>Karpinski, M.</creatorcontrib><creatorcontrib>Goldberg, A.</creatorcontrib><creatorcontrib>Storsley, L.</creatorcontrib><creatorcontrib>Rush, D. N.</creatorcontrib><creatorcontrib>Nickerson, P. W.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wiebe, C.</au><au>Gibson, I. W.</au><au>Blydt‐Hansen, T. D.</au><au>Pochinco, D.</au><au>Birk, P. E.</au><au>Ho, J.</au><au>Karpinski, M.</au><au>Goldberg, A.</au><au>Storsley, L.</au><au>Rush, D. N.</au><au>Nickerson, P. W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rates and Determinants of Progression to Graft Failure in Kidney Allograft Recipients With De Novo Donor‐Specific Antibody</atitle><jtitle>American journal of transplantation</jtitle><addtitle>Am J Transplant</addtitle><date>2015-11</date><risdate>2015</risdate><volume>15</volume><issue>11</issue><spage>2921</spage><epage>2930</epage><pages>2921-2930</pages><issn>1600-6135</issn><eissn>1600-6143</eissn><abstract>Understanding rates and determinants of clinical pathologic progression for recipients with de novo donor‐specific antibody (dnDSA), especially subclinical dnDSA, may identify surrogate endpoints and inform clinical trial design. A consecutive cohort of 508 renal transplant recipients (n = 64 with dnDSA) was studied. Recipients (n = 388) without dnDSA or dysfunction had an eGFR decline of −0.65 mL/min/1.73 m2/year. In recipients with dnDSA, the rate eGFR decline was significantly increased prior to dnDSA onset (−2.89 vs. −0.65 mL/min/1.73 m2/year, p < 0.0001) and accelerated post‐dnDSA (−3.63 vs. −2.89 mL/min/1.73 m2/year, p < 0.0001), suggesting that dnDSA is both a marker and contributor to ongoing alloimmunity. Time to 50% post‐dnDSA graft loss was longer in recipients with subclinical versus a clinical dnDSA phenotype (8.3 vs. 3.3 years, p < 0.0001). Analysis of 1091 allograft biopsies found that dnDSA and time independently predicted chronic glomerulopathy (cg), but not interstitial fibrosis and tubular atrophy (IFTA). Early T cell–mediated rejection, nonadherence, and time were multivariate predictors of IFTA. Independent risk factors for post‐dnDSA graft survival available prior to, or at the time of, dnDSA detection were delayed graft function, nonadherence, dnDSA mean fluorescence intensity sum score, tubulitis, and cg. Ultimately, dnDSA is part of a continuum of mixed alloimmune‐mediated injury, which requires solutions targeting T and B cells.
In this study, the authors analyze clinical and histologic risk factors available at the time of de novo donor‐specific antibody detection to determine clinical and histologic predictors of subsequent allograft failure, and their importance for clinical trial design.</abstract><cop>United States</cop><pub>Elsevier Limited</pub><pmid>26096305</pmid><doi>10.1111/ajt.13347</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acute Disease Adult Age Factors Alloantibody Allografts - immunology Child Child, Preschool Chronic Disease Clinical trials Cohort Studies compliance/adherence Delayed Graft Function - immunology Disease Progression Follow-Up Studies Graft Rejection - immunology Graft Rejection - pathology Health risk assessment Humans Isoantibodies - analysis Isoantibodies - immunology Kaplan-Meier Estimate Kidney Transplantation - adverse effects Kidney Transplantation - methods Male Middle Aged Multivariate Analysis Predictive Value of Tests Proportional Hazards Models rejection: antibody‐mediated (ABMR) rejection: chronic rejection: T cell–mediated (TCMR) Retrospective Studies Risk Assessment Sex Factors Statistics, Nonparametric T-Lymphocytes, Regulatory - immunology Time Factors Transplant Recipients Treatment Outcome |
| title | Rates and Determinants of Progression to Graft Failure in Kidney Allograft Recipients With De Novo Donor‐Specific Antibody |
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