Angiotensin II type I receptor agonistic autoantibodies are associated with poor allograft survival in liver retransplantation

Angiotensin II type I receptor (AT1R) agonistic autoantibodies (AT1R‐AA) are detrimental to kidney transplantation. Early studies suggested a similar negative effect in primary liver transplantation. Here, we studied AT1R‐AA in a retrospective cohort of 94 patients who received a second liver transp...

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Veröffentlicht in:American journal of transplantation 2020-01, Vol.20 (1), p.282-288
Hauptverfasser: Xu, Qingyong, McAlister, Vivian C., Leckie, Steve, House, Andrew A., Skaro, Anton, Marotta, Paul
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container_start_page 282
container_title American journal of transplantation
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creator Xu, Qingyong
McAlister, Vivian C.
Leckie, Steve
House, Andrew A.
Skaro, Anton
Marotta, Paul
description Angiotensin II type I receptor (AT1R) agonistic autoantibodies (AT1R‐AA) are detrimental to kidney transplantation. Early studies suggested a similar negative effect in primary liver transplantation. Here, we studied AT1R‐AA in a retrospective cohort of 94 patients who received a second liver transplant to determine their prevalence and effects. The concentrations of preformed AT1R‐AA before transplantation were higher (P = .019) in the 48 patients who lost their liver grafts than in the 46 patients whose grafts survived. About half (48/94, 51.1%) of the patients were positive for AT1R‐AA >17 U/mL before the second liver transplantation. In 22 (23.4%) patients, strong positive AT1R‐AA (defined as >40 U/mL) were detected, of whom 16 (72.7%) patients lost their grafts. Based on Kaplan‐Meier analysis, patients with strong positive AT1R‐AA had significantly worse graft survival than those with AT1R‐AA 40 U/mL (HR = 1.999 [1.085‐3.682], P = .026) or increased concentrations of AT1R‐AA (HR = 1.003 [1.001‐1.006] per incremental U/mL, P = .019) were significantly associated with elevated risk for graft loss. In conclusion, our data indicate that there is a high prevalence of AT1R‐AA in candidates for second liver transplantation and that their presence is associated with inferior long‐term outcomes of the second graft. In this retrospective study, Xu and colleagues demonstrate that agonistic autoantibodies to the angiotensin II type I receptor are common before second liver transplantation and, at high concentration, are associated with inferior survival of the second graft.
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Early studies suggested a similar negative effect in primary liver transplantation. Here, we studied AT1R‐AA in a retrospective cohort of 94 patients who received a second liver transplant to determine their prevalence and effects. The concentrations of preformed AT1R‐AA before transplantation were higher (P = .019) in the 48 patients who lost their liver grafts than in the 46 patients whose grafts survived. About half (48/94, 51.1%) of the patients were positive for AT1R‐AA &gt;17 U/mL before the second liver transplantation. In 22 (23.4%) patients, strong positive AT1R‐AA (defined as &gt;40 U/mL) were detected, of whom 16 (72.7%) patients lost their grafts. Based on Kaplan‐Meier analysis, patients with strong positive AT1R‐AA had significantly worse graft survival than those with AT1R‐AA &lt;40 U/mL (P = .035). In multivariate Cox models that included confounders such as sex and age, either AT1R‐AA &gt;40 U/mL (HR = 1.999 [1.085‐3.682], P = .026) or increased concentrations of AT1R‐AA (HR = 1.003 [1.001‐1.006] per incremental U/mL, P = .019) were significantly associated with elevated risk for graft loss. In conclusion, our data indicate that there is a high prevalence of AT1R‐AA in candidates for second liver transplantation and that their presence is associated with inferior long‐term outcomes of the second graft. In this retrospective study, Xu and colleagues demonstrate that agonistic autoantibodies to the angiotensin II type I receptor are common before second liver transplantation and, at high concentration, are associated with inferior survival of the second graft.</description><identifier>ISSN: 1600-6135</identifier><identifier>EISSN: 1600-6143</identifier><identifier>DOI: 10.1111/ajt.15571</identifier><identifier>PMID: 31419065</identifier><language>eng</language><publisher>United States: Elsevier Limited</publisher><subject>Adult ; Allografts ; Angiotensin ; Angiotensin II ; Autoantibodies ; Autoantibodies - adverse effects ; autoantibody ; clinical research/practice ; Female ; Follow-Up Studies ; Graft Rejection - etiology ; Graft Rejection - mortality ; Graft Rejection - pathology ; Graft Survival ; Humans ; immunobiology ; Kidney transplantation ; Liver ; liver allograft function/dysfunction ; Liver Diseases - mortality ; Liver Diseases - surgery ; Liver transplantation ; Liver Transplantation - adverse effects ; Liver Transplantation - mortality ; liver transplantation/hepatology ; Liver transplants ; Male ; Prognosis ; Receptor, Angiotensin, Type 1 - agonists ; Receptor, Angiotensin, Type 1 - immunology ; Reoperation ; retransplantation ; Retrospective Studies ; Risk Factors ; Survival ; Survival Rate ; translational research/science ; Transplantation, Homologous ; Transplants &amp; implants</subject><ispartof>American journal of transplantation, 2020-01, Vol.20 (1), p.282-288</ispartof><rights>2019 The American Society of Transplantation and the American Society of Transplant Surgeons</rights><rights>2019 The American Society of Transplantation and the American Society of Transplant Surgeons.</rights><rights>2020 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-c3531-6daaedf978140a5654ff17cf2f6b5351eaa7e854c8c780f0c4b2724778e8347e3</citedby><cites>FETCH-LOGICAL-c3531-6daaedf978140a5654ff17cf2f6b5351eaa7e854c8c780f0c4b2724778e8347e3</cites><orcidid>0000-0003-0579-1924</orcidid></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.15571$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fajt.15571$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31419065$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Qingyong</creatorcontrib><creatorcontrib>McAlister, Vivian C.</creatorcontrib><creatorcontrib>Leckie, Steve</creatorcontrib><creatorcontrib>House, Andrew A.</creatorcontrib><creatorcontrib>Skaro, Anton</creatorcontrib><creatorcontrib>Marotta, Paul</creatorcontrib><title>Angiotensin II type I receptor agonistic autoantibodies are associated with poor allograft survival in liver retransplantation</title><title>American journal of transplantation</title><addtitle>Am J Transplant</addtitle><description>Angiotensin II type I receptor (AT1R) agonistic autoantibodies (AT1R‐AA) are detrimental to kidney transplantation. Early studies suggested a similar negative effect in primary liver transplantation. Here, we studied AT1R‐AA in a retrospective cohort of 94 patients who received a second liver transplant to determine their prevalence and effects. The concentrations of preformed AT1R‐AA before transplantation were higher (P = .019) in the 48 patients who lost their liver grafts than in the 46 patients whose grafts survived. About half (48/94, 51.1%) of the patients were positive for AT1R‐AA &gt;17 U/mL before the second liver transplantation. In 22 (23.4%) patients, strong positive AT1R‐AA (defined as &gt;40 U/mL) were detected, of whom 16 (72.7%) patients lost their grafts. Based on Kaplan‐Meier analysis, patients with strong positive AT1R‐AA had significantly worse graft survival than those with AT1R‐AA &lt;40 U/mL (P = .035). In multivariate Cox models that included confounders such as sex and age, either AT1R‐AA &gt;40 U/mL (HR = 1.999 [1.085‐3.682], P = .026) or increased concentrations of AT1R‐AA (HR = 1.003 [1.001‐1.006] per incremental U/mL, P = .019) were significantly associated with elevated risk for graft loss. In conclusion, our data indicate that there is a high prevalence of AT1R‐AA in candidates for second liver transplantation and that their presence is associated with inferior long‐term outcomes of the second graft. 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Early studies suggested a similar negative effect in primary liver transplantation. Here, we studied AT1R‐AA in a retrospective cohort of 94 patients who received a second liver transplant to determine their prevalence and effects. The concentrations of preformed AT1R‐AA before transplantation were higher (P = .019) in the 48 patients who lost their liver grafts than in the 46 patients whose grafts survived. About half (48/94, 51.1%) of the patients were positive for AT1R‐AA &gt;17 U/mL before the second liver transplantation. In 22 (23.4%) patients, strong positive AT1R‐AA (defined as &gt;40 U/mL) were detected, of whom 16 (72.7%) patients lost their grafts. Based on Kaplan‐Meier analysis, patients with strong positive AT1R‐AA had significantly worse graft survival than those with AT1R‐AA &lt;40 U/mL (P = .035). In multivariate Cox models that included confounders such as sex and age, either AT1R‐AA &gt;40 U/mL (HR = 1.999 [1.085‐3.682], P = .026) or increased concentrations of AT1R‐AA (HR = 1.003 [1.001‐1.006] per incremental U/mL, P = .019) were significantly associated with elevated risk for graft loss. In conclusion, our data indicate that there is a high prevalence of AT1R‐AA in candidates for second liver transplantation and that their presence is associated with inferior long‐term outcomes of the second graft. In this retrospective study, Xu and colleagues demonstrate that agonistic autoantibodies to the angiotensin II type I receptor are common before second liver transplantation and, at high concentration, are associated with inferior survival of the second graft.</abstract><cop>United States</cop><pub>Elsevier Limited</pub><pmid>31419065</pmid><doi>10.1111/ajt.15571</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0003-0579-1924</orcidid><oa>free_for_read</oa></addata></record>
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source MEDLINE; Wiley Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects Adult
Allografts
Angiotensin
Angiotensin II
Autoantibodies
Autoantibodies - adverse effects
autoantibody
clinical research/practice
Female
Follow-Up Studies
Graft Rejection - etiology
Graft Rejection - mortality
Graft Rejection - pathology
Graft Survival
Humans
immunobiology
Kidney transplantation
Liver
liver allograft function/dysfunction
Liver Diseases - mortality
Liver Diseases - surgery
Liver transplantation
Liver Transplantation - adverse effects
Liver Transplantation - mortality
liver transplantation/hepatology
Liver transplants
Male
Prognosis
Receptor, Angiotensin, Type 1 - agonists
Receptor, Angiotensin, Type 1 - immunology
Reoperation
retransplantation
Retrospective Studies
Risk Factors
Survival
Survival Rate
translational research/science
Transplantation, Homologous
Transplants & implants
title Angiotensin II type I receptor agonistic autoantibodies are associated with poor allograft survival in liver retransplantation
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