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Publisher: John Wiley and Sons   (Total: 1579 journals)

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Showing 1 - 200 of 1579 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 12, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 65, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 46, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 51, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 153, SJR: 0.101, h-index: 9)
Acta Geologica Sinica (English Edition)     Hybrid Journal   (Followers: 3, SJR: 0.552, h-index: 41)
Acta Neurologica Scandinavica     Hybrid Journal   (Followers: 5, SJR: 1.203, h-index: 74)
Acta Obstetricia et Gynecologica Scandinavica     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 5, SJR: 0.112, h-index: 1)
Acta Paediatrica     Hybrid Journal   (Followers: 56, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 6, SJR: 1.69, h-index: 88)
Acta Polymerica     Hybrid Journal   (Followers: 9)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 35, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 6, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 4)
Addiction     Hybrid Journal   (Followers: 35, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 13, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 26, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 26, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 50, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 13, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 258, SJR: 9.021, h-index: 345)
Advanced Materials Interfaces     Hybrid Journal   (Followers: 6, SJR: 1.177, h-index: 10)
Advanced Optical Materials     Hybrid Journal   (Followers: 5, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 5)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 17, SJR: 2.729, h-index: 121)
Advances in Polymer Technology     Hybrid Journal   (Followers: 13, SJR: 0.344, h-index: 31)
Africa Confidential     Hybrid Journal   (Followers: 19)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 12)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 9)
African Development Review     Hybrid Journal   (Followers: 34, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 15, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 10, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 6, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 15, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 45, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 30, SJR: 1.122, h-index: 120)
Alcoholism and Drug Abuse Weekly     Hybrid Journal   (Followers: 7)
Alcoholism Clinical and Experimental Research     Hybrid Journal   (Followers: 7, SJR: 1.416, h-index: 125)
Alimentary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 33, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 50, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 140, SJR: 0.951, h-index: 61)
American Business Law J.     Hybrid Journal   (Followers: 24, SJR: 0.205, h-index: 17)
American Ethnologist     Hybrid Journal   (Followers: 90, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 28, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 33, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 12, SJR: 1.018, h-index: 58)
American J. of Industrial Medicine     Hybrid Journal   (Followers: 16, SJR: 0.993, h-index: 85)
American J. of Medical Genetics Part A     Hybrid Journal   (Followers: 16, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 4, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 6, SJR: 2.315, h-index: 79)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 37, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 271, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 63)
American J. of Reproductive Immunology     Hybrid Journal   (Followers: 3, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 17, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 131, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 10, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 16)
Anatomia, Histologia, Embryologia: J. of Veterinary Medicine Series C     Hybrid Journal   (Followers: 3, SJR: 0.295, h-index: 27)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1, SJR: 0.633, h-index: 24)
Andrologia     Hybrid Journal   (Followers: 2, SJR: 0.528, h-index: 45)
Andrology     Hybrid Journal   (Followers: 2, SJR: 0.979, h-index: 14)
Angewandte Chemie     Hybrid Journal   (Followers: 169)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 216, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 38, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 8, SJR: 0.957, h-index: 67)
Animal Science J.     Hybrid Journal   (Followers: 6, SJR: 0.569, h-index: 24)
Annalen der Physik     Hybrid Journal   (Followers: 5, SJR: 1.46, h-index: 40)
Annals of Anthropological Practice     Partially Free   (Followers: 2, SJR: 0.187, h-index: 5)
Annals of Applied Biology     Hybrid Journal   (Followers: 7, SJR: 0.816, h-index: 56)
Annals of Clinical and Translational Neurology     Open Access   (Followers: 1)
Annals of Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 47, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 2, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 9, SJR: 0.336, h-index: 23)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5, SJR: 2.389, h-index: 189)
Annual Bulletin of Historical Literature     Hybrid Journal   (Followers: 13)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 25, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 17, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 15)
Anthropology of Consciousness     Hybrid Journal   (Followers: 11, SJR: 0.172, h-index: 5)
Anthropology of Work Review     Hybrid Journal   (Followers: 11, SJR: 0.256, h-index: 5)
Anthropology Today     Hybrid Journal   (Followers: 91, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 47, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 7, SJR: 0.432, h-index: 59)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apmis     Hybrid Journal   (Followers: 1, SJR: 0.855, h-index: 73)
Applied Cognitive Psychology     Hybrid Journal   (Followers: 69, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 176, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 49, SJR: 0.868, h-index: 13)
Applied Stochastic Models in Business and Industry     Hybrid Journal   (Followers: 5, SJR: 0.613, h-index: 24)
Aquaculture Nutrition     Hybrid Journal   (Followers: 14, SJR: 1.025, h-index: 55)
Aquaculture Research     Hybrid Journal   (Followers: 31, SJR: 0.807, h-index: 60)
Aquatic Conservation Marine and Freshwater Ecosystems     Hybrid Journal   (Followers: 36, SJR: 1.047, h-index: 57)
Arabian Archaeology and Epigraphy     Hybrid Journal   (Followers: 11, SJR: 0.453, h-index: 11)
Archaeological Prospection     Hybrid Journal   (Followers: 12, SJR: 0.922, h-index: 21)
Archaeology in Oceania     Hybrid Journal   (Followers: 13, SJR: 0.745, h-index: 18)
Archaeometry     Hybrid Journal   (Followers: 27, SJR: 0.809, h-index: 48)
Archeological Papers of The American Anthropological Association     Hybrid Journal   (Followers: 15, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 25, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 4, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 4)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (SJR: 0.768, h-index: 54)
Area     Hybrid Journal   (Followers: 12, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 238, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 51, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 27, SJR: 2.256, h-index: 114)
Artificial Organs     Hybrid Journal   (Followers: 1, SJR: 0.872, h-index: 60)
ASHE Higher Education Reports     Hybrid Journal   (Followers: 14)
Asia & the Pacific Policy Studies     Open Access   (Followers: 15)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 314, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (Followers: 1, SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 8, SJR: 0.345, h-index: 20)
Asia-pacific J. of Clinical Oncology     Hybrid Journal   (Followers: 6, SJR: 0.554, h-index: 14)
Asia-Pacific J. of Financial Studies     Hybrid Journal   (SJR: 0.241, h-index: 7)
Asia-Pacific Psychiatry     Hybrid Journal   (Followers: 4, SJR: 0.377, h-index: 7)
Asian Economic J.     Hybrid Journal   (Followers: 8, SJR: 0.234, h-index: 21)
Asian Economic Policy Review     Hybrid Journal   (Followers: 4, SJR: 0.196, h-index: 12)
Asian J. of Control     Hybrid Journal   (SJR: 0.862, h-index: 34)
Asian J. of Endoscopic Surgery     Hybrid Journal   (SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 5, SJR: 1.443, h-index: 19)
Asian J. of Social Psychology     Hybrid Journal   (Followers: 5, SJR: 0.665, h-index: 37)
Asian Politics and Policy     Hybrid Journal   (Followers: 12, SJR: 0.207, h-index: 7)
Asian Social Work and Policy Review     Hybrid Journal   (Followers: 5, SJR: 0.318, h-index: 5)
Asian-pacific Economic Literature     Hybrid Journal   (Followers: 5, SJR: 0.168, h-index: 15)
Assessment Update     Hybrid Journal   (Followers: 4)
Astronomische Nachrichten     Hybrid Journal   (Followers: 2, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 29, SJR: 1.332, h-index: 27)
Austral Ecology     Hybrid Journal   (Followers: 14, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 9, SJR: 0.524, h-index: 28)
Australasian J. of Dermatology     Hybrid Journal   (Followers: 8, SJR: 0.714, h-index: 40)
Australasian J. On Ageing     Hybrid Journal   (Followers: 7, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 13, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 4, SJR: 0.709, h-index: 14)
Australian and New Zealand J. of Family Therapy (ANZJFT)     Hybrid Journal   (Followers: 3, SJR: 0.382, h-index: 12)
Australian and New Zealand J. of Obstetrics and Gynaecology     Hybrid Journal   (Followers: 46, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 11, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 7, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 4, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 29, SJR: 0.23, h-index: 9)
Australian Economic Review     Hybrid Journal   (Followers: 6, SJR: 0.357, h-index: 21)
Australian Endodontic J.     Hybrid Journal   (Followers: 3, SJR: 0.513, h-index: 24)
Australian J. of Agricultural and Resource Economics     Hybrid Journal   (Followers: 3, SJR: 0.765, h-index: 36)
Australian J. of Grape and Wine Research     Hybrid Journal   (Followers: 5, SJR: 0.879, h-index: 56)
Australian J. of Politics & History     Hybrid Journal   (Followers: 14, SJR: 0.203, h-index: 14)
Australian J. of Psychology     Hybrid Journal   (Followers: 18, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 406, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 5, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 71, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 12, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 19, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 32, SJR: 2.126, h-index: 39)
Autonomic & Autacoid Pharmacology     Hybrid Journal   (SJR: 0.371, h-index: 29)
Banks in Insurance Report     Hybrid Journal   (Followers: 1)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 10, SJR: 0.539, h-index: 70)
Basic and Applied Pathology     Open Access   (Followers: 2, SJR: 0.113, h-index: 4)
Basin Research     Hybrid Journal   (Followers: 5, SJR: 1.54, h-index: 60)
Bauphysik     Hybrid Journal   (Followers: 2, SJR: 0.194, h-index: 5)
Bauregelliste A, Bauregelliste B Und Liste C     Hybrid Journal  
Bautechnik     Hybrid Journal   (Followers: 1, SJR: 0.321, h-index: 11)
Behavioral Interventions     Hybrid Journal   (Followers: 9, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 24, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 9, SJR: 0.11, h-index: 5)
Beton- und Stahlbetonbau     Hybrid Journal   (Followers: 2, SJR: 0.493, h-index: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6, SJR: 0.311, h-index: 26)
Bioelectromagnetics     Hybrid Journal   (Followers: 1, SJR: 0.568, h-index: 64)
Bioengineering & Translational Medicine     Open Access  
BioEssays     Hybrid Journal   (Followers: 10, SJR: 3.104, h-index: 155)
Bioethics     Hybrid Journal   (Followers: 14, SJR: 0.686, h-index: 39)
Biofuels, Bioproducts and Biorefining     Hybrid Journal   (Followers: 1, SJR: 1.725, h-index: 56)
Biological J. of the Linnean Society     Hybrid Journal   (Followers: 16, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 3, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 42, SJR: 0.12, h-index: 1)
Biology of the Cell     Full-text available via subscription   (Followers: 9, SJR: 1.812, h-index: 69)
Biomedical Chromatography     Hybrid Journal   (Followers: 6, SJR: 0.572, h-index: 49)
Biometrical J.     Hybrid Journal   (Followers: 5, SJR: 0.784, h-index: 44)
Biometrics     Hybrid Journal   (Followers: 36, SJR: 1.906, h-index: 96)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 10, SJR: 0.715, h-index: 44)
Biopolymers     Hybrid Journal   (Followers: 18, SJR: 1.199, h-index: 104)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 45, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 179, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 14, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 20, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 9, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 37, SJR: 0.763, h-index: 64)
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 2, SJR: 0.727, h-index: 77)
Birth Defects Research Part B: Developmental and Reproductive Toxicology     Hybrid Journal   (Followers: 5, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)
BJOG : An Intl. J. of Obstetrics and Gynaecology     Partially Free   (Followers: 234, SJR: 2.083, h-index: 125)

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Journal Cover American Journal of Transplantation
  [SJR: 2.792]   [H-I: 140]   [17 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 1600-6135 - ISSN (Online) 1600-6143
   Published by John Wiley and Sons Homepage  [1579 journals]
  • Macrophage subpopulations and their impact on chronic allograft rejection
           versus graft acceptance in a mouse heart transplant model
    • Authors: Yue Zhao; Song Chen, Peixiang Lan, Chenglin Wu, Yaling Dou, Xiang Xiao, Zhiqiang Zhang, Laurie Minze, Xiaoshun He, Wenhao Chen, Xian C. Li
      Abstract: Macrophages infiltrating the allografts are heterogeneous, consisting of pro-inflammatory (M1 cells) as well as anti-inflammatory and fibrogenic phenotypes (M2 cells); they affect transplant outcomes via diverse mechanisms. Herein, we found that macrophage polarization into M1 and M2 subsets was critically dependent on TRAF6 and mTOR, respectively. In a heart transplant model we showed that macrophage-specific deletion of TRAF6 (LysMCreTraf6fl/fl) or mTOR (LysMCreMtorfl/fl) did not affect acute allograft rejection. However, treatment of LysMCreMtorfl/fl recipients with CTLA4-Ig induced long-term allograft survival (>100 days) without histological signs of chronic rejection, whereas the similarly treated LysMCreTraf6fl/fl recipients developed severe transplant vasculopathy (chronic rejection). The presentation of chronic rejection in CTLA4-Ig treated LysMCreTraf6fl/fl mice was similar to that of CTLA4-Ig treated wild type B6 recipients. Mechanistically, we found that the graft infiltrating macrophages in LysMCreMtorfl/fl recipients expressed high levels of PD-L1, and PD-L1 blockade readily induced rejection of otherwise survival grafts in the LysMCreMtorfl/fl recipients. Our findings demonstrate that targeting mTOR-dependent M2 cells is critical in preventing chronic allograft rejection and that graft survival under such conditions is dependent on the PD-1/PD-L1 co-inhibitory pathway.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-17T07:06:09.072861-05:
      DOI: 10.1111/ajt.14543
  • Outside-in HLA class I signaling regulates ICAM-1 clustering and
           endothelial-monocyte interactions via mTOR in transplant antibody-mediated
    • Authors: Sahar Salehi; Rebecca A. Sosa, Yi-Ping Jin, Shoichi Kageyama, Michael C. Fishbein, Enrique Rozengurt, Jerzy W. Kupiec-Weglinski, Elaine F. Reed
      Abstract: Antibody-mediated rejection (AMR) resulting in transplant allograft vasculopathy (TAV) is the major obstacle for long-term survival of solid organ transplants. AMR is caused by donor-specific antibodies to HLA which contribute to TAV by initiating outside-in signaling transduction pathways that elicit monocyte recruitment to activated endothelium. Mechanistic target of rapamycin (mTOR) inhibitors can attenuate TAV; therefore, we sought to understand the mechanistic underpinnings of mTOR signaling in HLA class I Ab-mediated endothelial cell activation and monocyte recruitment. We used an in vitro model to assess monocyte binding to HLA I Ab-activated endothelial cells and found mTOR inhibition reduced Ezrin/Radixin/Moesin (ERM) phosphorylation, ICAM-1 clustering and monocyte firm adhesion to HLA I Ab-activated endothelium. Further, in a mouse model of AMR, in which B6.RAG1-/- recipients of BALB/c cardiac allografts were passively transferred with donor-specific MHC I antibodies, mTOR inhibition significantly reduced vascular injury, ERM phosphorylation, and macrophage infiltration of the allograft. Taken together, these studies indicate mTOR inhibition suppresses ERM phosphorylation in endothelial cells which impedes ICAM-1 clustering in response to HLA class I Ab, and prevents macrophage infiltration into cardiac allografts. These findings indicate a novel therapeutic application for mTOR inhibitors to disrupt endothelial-monocyte interactions during AMR.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-17T07:06:00.532596-05:
      DOI: 10.1111/ajt.14544
  • Use of thrombolytic therapy in DCD liver transplantation does not seem to
           improve outcome
    • Authors: Lars Pietersen; Bart van Hoek, Andries Erik Braat
      Abstract: With great interest we read the article by Bohorquez et al. “Safety and Outcomes in 100 Consecutive Donation After Circulatory Death Liver Transplants Using a Protocol That Includes Thrombolytic Therapy” (1). The authors compared 100 consecutive donation after circulatory death (DCD) liver transplantations (LT) using a protocol that includes thrombolytic therapy (late DCD group) to a historical DCD group (early DCD group) and a cohort of donation after brain death (DBD) LT. The primary objective of the study was to “present the experience with 100 consecutive DCD LT using a protocol that includes tissue plasminogen activator (tPA) administration”.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-17T07:05:43.555096-05:
      DOI: 10.1111/ajt.14545
  • Beneficial effect of recombinant rC1rC2 collagenases on human islet
           function: Efficacy of low dose enzymes on pancreas digestion and yield
    • Authors: Gopalakrishnan Loganathan; Subhashree Venugopal, Andrew G. Breite, William W. Tucker, Siddharth Narayanan, Maheswaran Dhanasekaran, SriPrakash Mokshagundam, Michael L. Green, Michael G. Hughes, Stuart K. Williams, Francis E. Dwulet, Robert C. McCarthy, Appakalai N Balamurugan
      Abstract: High number of human islets can be isolated using modern purified tissue dissociation enzymes, however it requires using>20 Wunsch Unit (WU)/gram of pancreas for digestion. Attempts to reduce this dose have resulted in pancreas under-digestion and poor islet recovery but improved islet function. In this study, we achieved high number of functional islets using low dose of recombinant collagenase enzyme mixture (RCEM). The collagenase dose used in these isolations is about 42% of the natural collagenase enzyme mixture (NCEM) dose commonly used to digest a 100g pancreas. Low dose RCEM was efficient in digesting entire pancreases to obtain higher yield (5,535±830 IEQ/gram and 2,582±925 IEQ/gram, P
      PubDate: 2017-10-16T11:25:18.928893-05:
      DOI: 10.1111/ajt.14542
  • Impact of spontaneous donor hypothermia on graft outcomes after kidney
    • Authors: P Schnuelle; H M Mundt, F Drüschler, W H Schmitt, B A Yard, B K Krämer, U Benck
      Abstract: A previous donor intervention trial found that therapeutic hypothermia reduced delayed graft function (DGF) after kidney transplantation. This retrospective cohort study nested in the randomized dopamine trial (ClinicalTrials. gov identifier: NCT000115115) investigates the effects of spontaneous donor hypothermia (core body temperature
      PubDate: 2017-10-12T22:55:27.453147-05:
      DOI: 10.1111/ajt.14541
  • Prevalence and outcomes of cystic lesions of the transplant pancreas: The
           University of Wisconsin Experience
    • Authors: Talal M Al-Qaoud; Eric J Martinez, Hans W Sollinger, Dixon B Kaufman, Robert R Redfield, Bridget Welch, Glen Leverson, Jon S Odorico
      Abstract: Literature on the behavior of cystic lesions in pancreas transplants is scarce, and hence a better understanding is warranted. Data on recipients and their respective donors that underwent simultaneous kidney and pancreas, pancreas transplant alone, and pancreas after kidney between 1994-2015 were reviewed (n=1185). Cystic lesions of the transplant pancreas developed in 22 patients (1.8%): 12 pseudocysts, 2 cysts/remnants, 4 intraductal papillary mucinous neoplasms (IPMN), 2 adenocarcinomas, 1 low grade intraepithelial pancreatic neoplasia, and 1 case of polycystic kidney disease. The median size was 3.6cm (1.6-5.5cm), and occurred at a median time of 65.5mos (2-183mos) post transplant. The median age of the graft at time of diagnosis was 42yrs (25.7-54.5), with 17 of 22 grafts (77%) functioning at time of diagnosis. Triggers for investigation were elevations in pancreatic enzymes, re-admissions for abdominal pain, and incidentalomas. High resolution imaging and diagnostic biopsy/aspiration with ancillary tests were the main diagnostic tests. Most pseudocysts were managed by percutaneous drainage, and although no firm inference can be made from such a small series, we have observed that the behavior and management of IPMN and adenocarcinoma in the pancreas graft appears congruent to that of the native pancreas.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-11T06:05:21.866989-05:
      DOI: 10.1111/ajt.14540
  • Human papillomavirus and post-transplant cutaneous squamous-cell
           carcinoma: a multicenter, prospective cohort study
    • Authors: Jan Nico Bouwes Bavinck; Mariet C. W. Feltkamp, Adele C. Green, Marta Fiocco, Sylvie Euvrard, Catherine A. Harwood, Charlotte M. Proby, Luigi Naldi, Janouk C. D. Diphoorn, Anna Venturuzzo, Gianpaolo Tessari, Ingo Nindl, Francesca Sampogna, Damiano Abeni, Rachel E Neale, Jelle J. Goeman, Koen D. Quint, Anne Berthe Halk, Carmen Sneek, Roel E. Genders, Maurits N. C. de Koning, Wim G.V. Quint, Ulrike Wieland, Sönke Weissenborn, Tim Waterboer, Michael Pawlita, Herbert Pfister,
      Abstract: Organ-transplant recipients (OTR) have a 100-fold increased risk of cutaneous squamous-cell carcinoma (cSCC). We prospectively evaluated the association between beta-genus human-papillomaviruses (betaPV) and keratinocyte carcinoma in OTR. Two OTR cohorts without cSCC were assembled: cohort 1 transplanted in 2003-2006 (n=274) and cohort 2 in 1986-2002 (n=352). Participants were followed until death or cessation of follow-up in 2016. BetaPV infection was assessed in eyebrow hairs using PCR-based methods. BetaPV IgG seroresponses were determined by multiplex serology. A competing risk model with delayed entry was used to estimate cumulative incidence of histologically proven cSCC and the effect of betaPV using a multivariable Cox regression model. Results are reported as adjusted hazard ratios (HR). OTR with ≥5 different betaPV types in eyebrow hairs had 1.7 times the risk of cSCC versus those with 0-4 different types (HR: 1.7 (1.1;2.6)). A similar risk was seen with high betaPV loads (HR: 1.8 (1.2;2.8)). No significant associations were seen between serum antibodies and cSCC or between betaPV and basal-cell carcinoma. The diversity and load of betaPV types in eyebrow hairs are associated with cSCC risk in OTR, providing evidence that betaPV is associated with cSCC carcinogenesis and may present a target for future preventive strategies.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-11T05:50:25.038713-05:
      DOI: 10.1111/ajt.14537
  • Healthcare utilization after liver transplantation is highly variable both
           among centers and recipients
    • Authors: T Bittermann; R. A Hubbard, M Serper, J. D Lewis, S. F Hohmann, L. B VanWagner, D. S Goldberg
      Abstract: The relationship between healthcare utilization before and after liver transplantation (LT) and its association with center characteristics is incompletely understood. This was a retrospective cohort study of 34,402 adult LTs between 2002-2013 using Vizient inpatient claims data linked to the United Network for Organ Sharing database. Multivariable mixed-effects linear regression models evaluated the association between hospitalization 90 days pre-LT and the number of days alive and out of the hospital (DAOH) 1 year post-LT. Of those alive at LT discharge, 24.7% spent ≥30 days hospitalized during the first year. Hospitalization in the 90 days pre-LT was inversely associated with DAOH (β=-3.4 DAOH/week hospitalized pre-LT; p=0.002). Centers with>30% of their LT recipients hospitalized ≥30 days in the first LT year were typically smaller volume and/or transplanting higher risk recipients (Model for End-Stage Liver Disease [MELD] score ≥35, inpatient or ventilated pre-LT). In conclusion, pre-LT hospitalization predicts 1-year post-LT hospitalization independent of MELD score at the patient-level, while center-specific post-LT healthcare utilization is associated with certain center behaviors and selection practices.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-11T02:45:18.874629-05:
      DOI: 10.1111/ajt.14539
  • Is the kidney donor profile index (KDPI) universal or UNOS-specific'
    • Authors: Burcin Ekser; John A. Powelson, Jonathan A. Fridell, William C. Goggins, Tim E. Taber
      Abstract: With the introduction of the KDPI scoring system on June 2013, allocation of kidney allografts and predicted outcomes in the United Network for Organ Sharing (UNOS) have changed. Although the hope was to reduce the discard rate of ‘marginal’ or ‘extended criteria donor (ECD)’ kidneys allocating them in a better way, the discard rate did not differ compared to the ECD era [1]. The transplantation community continues to seek ways to improve kidney allocation in order to provide acceptable (or even better) outcomes using the most possible deceased donor kidneys reducing the discard rate. One way to boost the use of higher risk kidneys is allocating them as dual kidney transplantation (DKT) [2]. DKT could provide increased nephron mass and therefore better expected outcomes compared to single use of ECD kidneys.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-11T02:40:45.418395-05:
      DOI: 10.1111/ajt.14538
  • The Role of C4d Deposition in the Diagnosis of Antibody-Mediated Rejection
           after Lung Transplantation
    • Authors: P R Aguilar; D Carpenter, J Ritter, R D Yusen, C A Witt, D E Byers, T Mohanakumar, D Kreisel, E P Trulock, R R Hachem
      Abstract: Antibody-mediated rejection (AMR) is an increasingly recognized form of lung rejection. C4d deposition has been an inconsistent finding in previous reports and its role in the diagnosis has been controversial. We conducted a retrospective single-center study to characterize cases of C4d-negative probable AMR and to compare these to cases of definite (C4d-positive) AMR. We identified 73 cases of AMR: 28 (38%) were C4d-positive and 45 (62%) were C4d-negative. The two groups had a similar clinical presentation, and although more patients in the C4d-positive group had neutrophilic capillaritis (54% vs. 29%, p = 0.035), there was no significant difference in the presence of other histologic findings. In spite of aggressive antibody-depleting therapy, 19 of 73 (26%) patients in the overall cohort died within 30 days, but there was no significant difference in freedom from chronic lung allograft dysfunction (CLAD) or survival between the two groups. We conclude that AMR may cause allograft failure, but the diagnosis requires a multidisciplinary approach and a high index of suspicion. C4d deposition does not appear to be a necessary criterion for the diagnosis, and although some cases may initially respond to therapy, there is a high incidence of CLAD and poor survival after AMR.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-09T14:50:33.644977-05:
      DOI: 10.1111/ajt.14534
  • Invited letter in response to “Predicted indirectly recognizable HLA
           epitopes (PIRCHE): only the tip of the iceberg'”
    • Authors: Nils Lachmann; Matthias Niemann, Petra Reinke, Klemens Budde, Danilo Schmidt, Fabian Halleck, Axel Pruß, Constanze Schönemann, Eric Spierings, Oliver Staeck
      Abstract: We thank Guidicelli et al. for sharing their valuable thoughts on our recent publication (1) and appreciate the suggestions and ideas for further improvements of PIRCHE-matching (2).Missing consideration of some allopeptides is a limitation of the version of PIRCHE used in this study. The latest version takes more HLA allopeptide sources into account (e.g. DQA1, DPA1 and more) which hopefully increases the predictive power of the algorithm. However, this feature could not be applied in our retrospective study, as the present dataset is incomplete for DQA and DP typings.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-09T14:50:30.951779-05:
      DOI: 10.1111/ajt.14535
  • Outcomes of Organ Transplants When the Donor Is a Prior Recipient
    • Authors: G. S. Lee; D. S. Goldberg, M.H. Levine, P. L. Abt
      Abstract: Organ shortage continues to challenge the field of transplantation. One potential group of donors are those who have been transplant recipients themselves, or Organ Donor After Transplant (ODAT). We conducted a retrospective cohort study to describe ODAT donors and to compare outcomes of ODAT grafts versus conventional grafts. From 10/1/87 to 6/30/15, 517 former recipients successfully donated 803 organs for transplant. Former kidney recipients generally survived a median of approximately four years before becoming an ODAT donor whereas liver, lung, and heart recipients generally survived less than a month prior to donation. In the period 1/1/05 to 12/31/14, liver grafts from ODAT donors had a significantly higher risk of graft failure compared to non-ODAT liver transplants (p = 0.008). Kidney grafts donated by ODAT donors whose initial transplant occurred>1 year prior were associated with significantly increased graft failure (p = 0.012). Despite increased risk of graft failure amongst certain ODAT grafts, five year survival was still high. ODAT donors should be considered another form of expanded criteria donor under these circumstances.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-09T14:50:27.946095-05:
      DOI: 10.1111/ajt.14536
  • A molecular biopsy test based on arteriolar under-hyalinosis reflects
           increased probability of rejection related to under-immunosuppression
    • Authors: Gunilla Einecke; Jeff Reeve, Philip F Halloran
      Abstract: Calcineurin inhibitor immunosuppressive drugs induce changes such as arteriolar hyalinosis (ah) in kidney transplants, raising the possibility that molecular changes in biopsies related to histologic ah can provide information about drug exposure. We hypothesized that molecular changes associated with less-than expected hyalinosis might highlight a subpopulation of patients with under-immunosuppression/non-adherence at intermediate times post-transplant (TxBx). Using gene expression data from 562 indication biopsies, we developed a molecular classifier for predicting the expected ah lesions (Mah) at a particular TxBx. Mah-scores increased linearly with log(TxBx), but some biopsies had lower scores than expected for TxBx. The deviation of individual Mah-scores below the predicted regression line of Mah-scores vs TxBx is defined as “low hyalinosis index”. Low hyalinosis indices were frequent in biopsies between 3 months and 3 years post-transplant, particularly among biopsies lacking histologic hyalinosis (ah0), and were associated with T cell-mediated rejection and a subset of recent onset antibody-mediated rejection without glomerular double contours. In patients with medical records available for review, low hyalinosis indices were frequently associated with physician-recorded concerns about non-adherence (suspected or proven). We conclude that the Mah classifier and hyalinosis index identify indication biopsies with rejection for which the possibility of patient non-adherence should be considered.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-06T08:40:28.209094-05:
      DOI: 10.1111/ajt.14532
  • Multidisciplinary Approach to Cardiac and Pulmonary Vascular Disease Risk
           Assessment in Liver Transplantation: An Evaluation of the Evidence and
           Consensus Recommendations
    • Authors: Lisa B. VanWagner; Matthew E. Harinstein, James R. Runo, Christopher Darling, Marina Serper, Shelley Hall, Jon A. Kobashigawa, Laura L. Hammel
      Abstract: Liver transplant (LT) candidates today are older, have greater medical severity of illness, and have more cardiovascular comorbidities than ever before. In addition, there are specific cardiovascular responses in cirrhosis that can be detrimental to the LT candidate. Cirrhotic cardiomyopathy, a condition characterized by increased cardiac output and a reduced ventricular response to stress, is present in up to 30% of patients with cirrhosis thus challenging perioperative management. Current noninvasive tests that assess for subclinical coronary and myocardial disease have low sensitivity, and altered hemodynamics during the LT surgery can unmask latent cardiovascular disease either intraoperatively or in the immediate postoperative period. Therefore, this review, assembled by a group of multidisciplinary experts in the field and endorsed by the American Society of Transplantation Liver and Intestine and Thoracic and Critical Care Communities of Practice, provides a critical assessment of the diagnosis of cardiac and pulmonary vascular disease and interventions aimed at managing these conditions in LT candidates. Key points and practice-based recommendations for the diagnosis and management of cardiac and pulmonary vascular disease in this population are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-06T08:35:57.341251-05:
      DOI: 10.1111/ajt.14531
  • Urologic Malignancies in Kidney Transplantation
    • Authors: Laura A. Hickman; Deirdre Sawinski, Thomas Guzzo, Jayme E. Locke
      Abstract: With advances in immunosuppression, graft and patient outcomes after kidney transplantation have improved considerably. As a result, long-term complications of transplant, such as urologic malignancies, have become increasingly important. Kidney transplant recipients, for example, have a seven-fold risk of renal cell carcinoma (RCC) and three-fold risk of urothelial carcinoma (UC) compared to the general population. While extrapolation of data from the general population suggest that routine cancer screening in transplant recipients would allow for earlier diagnosis and management of these potentially lethal malignancies, currently there is no consensus for post-transplant RCC or UC screening as supporting data are limited. Further understanding of risk factors, presentation, optimal management of and screening for urologic malignancies in kidney transplant patients is warranted, and as such, this review will focus on the incidence, surveillance, and treatment of urologic malignancies in kidney transplant recipients.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-06T08:35:55.546453-05:
      DOI: 10.1111/ajt.14533
  • External validation of prediction models for time to death in potential
           donors after circulatory death
    • Authors: A. M. M. Kotsopoulos; F. Böing-Messing, N. E. Jansen, P. Vos, W. F. Abdo
      Abstract: Predicting time to death in controlled donation after circulatory death (cDCD) donors following withdrawal of life-sustaining treatment (WLST) is important but poses a major challenge. The aim of this study is to determine factors predicting time to circulatory death within 60 minutes after WSLT and validate previously developed prediction models. In a single-center retrospective study we used the data of 92 potential cDCD donors. Multivariable regression analysis demonstrated that absent cough-, corneal reflex, lower morphine dosage, and midazolam use were significantly associated with death within 60 minutes (area under the curve (AUC) 0.89; 95% confidenence interval (CI) 0.87-0.91). External validation of the logistic regression models of de Groot et al (AUC 0.86; 95% CI 0.77-0.95), Wind et al (AUC 0.62; 95% CI 0.49-0.76), Davila et al (AUC 0.80; 95% CI 0.708-0.901) and the Cox regression model by Suntharalingam et al (Harrell's c-index 0.63), exhibited good discrimination and could fairly identify which patients died within 60 minutes. Previous prediction models did not incorporate the process of WLST. We believe that future studies should also include the process of WLST as an important predictor.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-05T03:40:20.977322-05:
      DOI: 10.1111/ajt.14529
  • Analysis of public discourse on heart transplantation in Japan using
           Social Network Service data
    • Authors: N. Nawa; H. Ishida, H. Suginobe, S. Katsuragi, H. Baden, K. Takahashi, J. Narita, S. Kogaki, K. Ozono
      Abstract: The clarification of public concerns regarding heart transplantation is important for improving low organ donation rates in Japan. In the present study, we used the Twitter data of 4986 (between August 2015 and January 2016) and 1429 tweets (between April 2016 and May 2016) to analyze public discourse on heart transplantation in Japan and identify the reasons for low organ donation rates. We manually categorized all tweets relevant to heart transplantation into nine categories and counted the number of tweets in each category per month. During the study period, the most popular category of tweets was related to the media followed by money (tweets questioning or even criticizing the high price of fundraising goals to go overseas for heart transplants), while some tweets were misconceptions. We also conducted a sentiment analysis, which revealed that the most popular negative tweets were related to money, while the most positive tweets were related to reports on the favorable outcomes of recipients. Our results suggest that listening to concerns, providing correct information (particularly for some misconceptions), and emphasizing the outcomes of recipients will facilitate an increase in the number of people contemplating heart transplantation and organ donation.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-05T03:26:35.277808-05:
      DOI: 10.1111/ajt.14527
  • The Duration of Asystolic Ischemia Time Determines the Risk of Graft
           Failure After Circulatory-Dead Donor Kidney Transplantation: a
           Eurotransplant Cohort Study
    • Authors: L Heylen; I Jochmans, U Samuel, I Tieken, M Naesens, J Pirenne, B Sprangers
      Abstract: Circulatory death donor (DCD) kidney transplantations are steadily increasing. Consensus reports recommend to limit donor warm ischemia time (DWIT) in DCD donation, although an independent effect on graft outcome has not been demonstrated. We investigated death-censored graft survival in 18,065 recipients of deceased-donor kidney transplants in the Eurotransplant region: 1,059 DCD and 17,006 brain-dead donor (DBD) kidney recipients. DWIT was defined as time from circulatory arrest until cold flush. DCD donation was an independent risk factor for graft failure (adjusted HR 1.28, 95%CI 1.10-1.46), due to an increased risk of primary non-function (62/1,059 versus 560/17,006; p
      PubDate: 2017-10-05T03:10:35.244442-05:
      DOI: 10.1111/ajt.14526
  • Anti-C1s Monoclonal Antibody BIVV009 in Late Antibody-Mediated Kidney
           Allograft Rejection - Results from a First-in-Patient Phase 1 Trial
    • Authors: F. Eskandary; B. Jilma, J. Mühlbacher, M. Wahrmann, H. Regele, N. Kozakowski, C. Firbas, S. Panicker, G. C. Parry, J. C. Gilbert, P. F. Halloran, G. A. Böhmig
      Abstract: The classical pathway (CP) of complement may contribute to the pathogenesis of antibody-mediated rejection (ABMR). Selective CP blockade may be a promising strategy to counteract rejection. The objective of this first-in-patient phase 1b trial was to evaluate the safety/tolerability and CP-blocking potential of four weekly doses (60 mg/kg) of the anti-C1s antibody BIVV009 in complement-mediated disorders. Here we describe the results in a cohort of 10 stable kidney transplant recipients (median of 4.3 years post-transplantation) with late active ABMR and features of CP activation, such as capillary C4d or complement-fixing donor-specific antibodies (DSA). During seven weeks follow-up, no severe adverse events were reported, and BIVV009 profoundly inhibited overall and DSA-triggered CP activation in serum. Five of eight C4d-positive recipients turned C4d-negative in 5-week follow-up biopsies, while another two recipients showed a substantial decrease in C4d scores. There was, however, no change in microcirculation inflammation, gene expression patterns, DSA levels, or kidney function. In conclusion, we demonstrate that BIVV009 effectively blocks alloantibody-triggered CP activation, even though short-course treatment had no effect on indices of activity in late ABMR. This initial trial provides a valuable basis for future studies designed to clarify the therapeutic value of CP blockade in transplantation. ClinicalTrials. gov NCT#02502903This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-05T02:45:26.183086-05:
      DOI: 10.1111/ajt.14528
  • Treatment for Presumed BK Polyomavirus Nephropathy and Risk of Urinary
           Tract Cancers among Kidney Transplant Recipients in the United States
    • Authors: Gaurav Gupta; Sarat Kuppachi, Roberto S. Kalil, Christopher B. Buck, Charles F. Lynch, Eric A. Engels
      Abstract: Recent case series describe detection of BK polyomavirus (BKV) in urinary tract cancers in kidney transplant recipients, suggesting that BKV could contribute to the development of these cancers. We assessed risk for urinary tract cancers in kidney recipients with or without treatment for presumed BKV nephropathy (tBKVN) using data from the United States Transplant Cancer Match Study (2003-2013). Among 55,697 included recipients, 2015 (3.6%) were reported with tBKVN. Relative to the general population, incidence was similarly elevated (approximately 4.5-fold) for kidney cancer in recipients with or without tBKVN, and incidence was not increased in either group for prostate cancer. In contrast, for invasive bladder cancer, incidence was more strongly elevated in recipients with versus without tBKVN (standardized incidence ratios 4.5 vs. 1.7; N=48 cases), corresponding to an incidence rate ratio (IRR) of 2.9 (95%CI 1.0-8.2), adjusted for sex, age, transplant year, and use of polyclonal antibody induction. As a result, recipients with tBKVN had borderline increased incidence for all urothelial cancers combined (renal pelvis, ureter, and bladder cancers: adjusted IRR 2.2, 95%CI 0.9-5.4; N=89 cases). Together with reports describing BKV detection in tumor tissues, these results support an association between BKV and urothelial carcinogenesis among kidney transplant recipients.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-05T02:40:19.866023-05:
      DOI: 10.1111/ajt.14530
  • GFR ≤25 Years Postdonation in Donors with (vs without) a 1st Degree
           Relative with ESRD
    • Authors: Arthur J. Matas; David M. Vock, Hassan N. Ibrahim
      Abstract: An increased risk of ESRD has been reported for living kidney donors, and appears to be higher for those donating to a relative. The reasons for this are not clear. One possibility is that ESRD may be due the nephrectomy-related reduction in GFR, followed by an age-related decline that may be more rapid in related donors. Between 1/1/1990 – 12/31/2014, we did 2002 living donor nephrectomies. We compared long-term postdonation eGFR trajectory for donors with (n=1245) versus without (n=757) a first-degree relative with ESRD. Linear mixed-effects models were used to model the longitudinal trajectory of eGFR. With all other variables held constant, there was a steady average increase in eGFR until donors reached age 70; 1.12 (95% CI: 0.92–1.32) ml/min/year between 6 weeks–5 years postdonation; 0.24 (0.00–0.49) ml/min/year between 5-10 years; and 0.07 (-0.10–+0.25) ml/min/year between 10-20 years for donors with attained age less than 70. After age 70, eGFR declined. After adjustment of predonation factors, the difference in eGFR slopes between related and unrelated donors was 0.20mL/min/1.75m2/year (0.07-0.33) Our data suggests that: postdonation, kidney donor eGFR increases each year for a number of years and that eGFR trajectory does not explain an increase in ESRD after donation.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-05T02:30:22.453203-05:
      DOI: 10.1111/ajt.14525
  • Palliative and end of life care in solid organ transplantation
    • Authors: Kirsten Wentlandt; Andrea Weiss, Erin O'Connor, Ebru Kaya
      Abstract: Palliative care is an interprofessional approach that focuses on quality of life of patients facing life-threatening illness. Palliative care is consistently associated with improvements in advance care planning, patient and caregiver satisfaction, quality of life, symptom burden, and lower health care utilization. Most transplant patients suffer from advanced chronic disease, significant symptom burden, and mortality awaiting transplant. Transplantation introduces new risks including perioperative death, organ rejection, infection, renal insufficiency, and malignancy. Numerous publications over the last decade identify that palliative care is well-suited to support these patients and their caregivers, yet access to palliative care and research within this population is lacking. This review describes palliative care and summarizes existing research supporting palliative intervention in advanced organ failure, and transplant populations. A proposed model to provide palliative care in parallel with disease directed therapy in a transplant program has potential to improve symptom burden, quality of life, and health care utilization. Further studies are needed to elucidate specific benefits of palliative care for this population. In addition, there is tremendous need for education, specifically for clinicians, patients, and families, to improve understanding of palliative care and its benefits for patients with advanced disease.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-04T04:35:28.968656-05:
      DOI: 10.1111/ajt.14522
  • CD47 Blockade Reduces Ischemia/Reperfusion Injury in Donation after
           Cardiac Death Rat Kidney Transplantation
    • Authors: Xuanchuan Wang; Min Xu, Jianluo Jia, Zhengyan Zhang, Joseph P. Gaut, Gundumi A. Upadhya, Pamela T. Manning, Yiing Lin, William C. Chapman
      Abstract: Modulation of nitric oxide (NO) activity through blockade of CD47 signaling has been shown to reduce ischemia-reperfusion injury (IRI) in various models of tissue ischemia. Here, we evaluate the potential effect of an antibody-mediated CD47 blockade in a syngeneic and an allogeneic DCD rat kidney transplant model. The donor organ was subjected to 1 hr of warm ischemia time after circulatory cessation, then flushed with a CD47 monoclonal antibody (CD47mAb) in the treatment group, or an isotype-matched immunoglobulin in the control group. We found that CD47mAb treatment improved survival rates in both models. Serum markers of renal injury were significantly decreased in the CD47mAb treated group compared with the control group. Histologically the CD47mAb treated group had significantly reduced scores of acute tubular injury and acute tubular necrosis. The expression of biomarkers related to mitochondrial stress and apoptosis also were significantly lower in the CD47mAb treated groups. Overall, the protective effects of CD47 blockade were greater in the syngeneic model. Our data show that CD47mAb blockade decreased the IRI of DCD kidneys in rat transplant models. This therapy has the potential to improve DCD kidney transplant outcomes in the human setting.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-04T01:15:24.085031-05:
      DOI: 10.1111/ajt.14523
  • Potential Yield of Imminent Death Kidney Donation
    • Authors: Ryan A. Denu; Eneida A. Mendonca, Norman Fost
      Abstract: About 99,000 people are waiting for a kidney in the US, and many will die waiting. The concept of “imminent death” donation, a type of living donation, has been gaining attention among physicians, patients, and ethicists. We estimated the number of potential imminent death kidney donors at the University of Wisconsin Hospital and Clinics by estimating the number of annual deaths in individuals with normal kidney function. Based on a previous survey suggesting that 1/3 of patients might be willing to donate at imminent death, we estimate that between 76 and 396 people in the state of Wisconsin would be medically eligible and willing to donate each year at the time of imminent death. We extrapolated these numbers to all transplant centers in the US, estimating that between 5925 and 31,097 people might be eligible and willing to donate. Our results suggest that allowing donation at imminent death and including discussions about organ donation in end-of-life planning could substantially reduce the nation's kidney waiting list while providing many more donors the opportunity to give this gift.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-04T01:15:22.134999-05:
      DOI: 10.1111/ajt.14524
  • American Journal of Transplantation: Volume 17, Number 10, October 2017
    • Abstract: On the cover this month: Long-term outcomes in transplantation remain suboptimal and difficult to anticipate. This month, we present numerous articles examining methods for assessing long-term outcomes, including an article by Asare et al (page 2627) relating a previously reported tolerance signature that appears to segregate with favorable outcomes in kidney recipients. This is accompanied by a cautionary editorial by Christakoudi and Hernandez-Fuentes (page 2505). Other articles by Park et al (page 2640), Francis et al (page 2650), van den Bosch et al (page 2659), and Shemesh et al (page 2668), provide numerous approaches to forecasting posttransplant complications. We also present a Comprehensive Review on skin cancer as part of our ongoing series of Cancer in Transplantation (page 2509). Cover design by Megan Llewellyn, Duke University Department of Surgery.
      PubDate: 2017-09-28T09:36:40.768346-05:
      DOI: 10.1111/ajt.14468
  • No Country for Old Livers' Examining and Optimizing the Utilization of
           Elderly Liver Grafts
    • Authors: K J Halazun; A A Rana, B Fortune, R C Quillan, E C Verna, B Samstein, J V Guarrera, T Kato, A D Griesemer, A Fox, R S Brown, J C Emond
      Abstract: Of the 1.6 million patients>70 who have died of stroke since 2002, donor livers were retrieved from only 2,402 (0.15% yield rate). Despite reports of successful liver transplantation (LT) with elderly grafts (EG), advanced donor age is considered a risk for poor outcomes. CMS definitions of an “eligible death” for donation excludes patients>70, creating disincentives to donation. We investigated utilization and outcomes of recipients of donors>70 through analysis of a UNOS STAR-file of adult-LTs from 2002 to 2014. Survival analysis was conducted using Kaplan-Meier curves, and Cox-regression was used to identify factors influencing outcomes of EG recipients. 3,104 livers>70 were included, ~40% of which were used in two regions; 2 (520/3104) & 9 (666/3104). Unadjusted survival was significantly worse among recipients of EG compared to recipients of younger grafts (p70, the yield rate of EGs can be maximized and disincentives removed to help resolve the organ shortage crisis.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-27T06:21:56.048064-05:
      DOI: 10.1111/ajt.14518
  • Temporal trends, center-level variation, and the impact of prevalent state
           obesity rates on acceptance of obese living kidney donors
    • Authors: Abhijit S. Naik; Diane M. Cibrik, Ankit Sakhuja, Milagros Samaniego, Yee Lu, Vahakn Shahinian, Silas P. Norman, Mark A. Schnitzler, Bertram L. Kasiske, Dorry L. Segev, Krista L. Lentine
      Abstract: The impact of predonation obesity on long-term outcomes of living kidney donors remains controversial. Published guidelines offer varying recommendations regarding body mass index (BMI, kg/m2) thresholds for donor acceptance. We examined temporal and center-level variation in BMI of accepted donors across US transplant centers. Using national transplant registry data, we performed multivariate hierarchical logistic regression modeling using pairwise comparisons (overweight, BMI 25-29.9; mildly obese, BMI 30-34.9; very obese, BMI>35; versus normal BMI, 18.5-24.9). Metrics of heterogeneity, including median odds ratio (MOR), were calculated. Among 90,013 living kidney donors, 2001-2016, proportions who were very obese decreased and proportions who were mildly obese or overweight increased. Significant center-level heterogeneity was noted in BMI of accepted donors; the MOR varyed from 1.10 for overweight to 1.93 for very obese donors. At centers located in the 10 states with the highest general population obesity rates, adjusted odds of very obese donor status were 185% higher (reference: normal BMI) than in states with the lowest obesity rates. Although there is a declining trend in acceptance of very obese living kidney donors, variation across centers is significant. Further, local population obesity rates may affect the decision to accept obese individuals as donors.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-26T04:21:23.764909-05:
      DOI: 10.1111/ajt.14519
  • Treatment of chronic antibody mediated rejection with intravenous
           immunoglobulins and rituximab: a multicenter, prospective, randomized,
           double blind clinical trial
    • Authors: Francesc Moreso; Marta Crespo, Juan C. Ruiz, Armando Torres, Alex Gutierrez-Dalmau, Antonio Osuna, Manel Perelló, Julio Pascual, Irina B. Torres, Dolores Redondo-Pachón, Emilio Rodrigo, Marcos Lopez-Hoyos, Daniel Seron
      Abstract: There are no approved treatments for chronic antibody mediated rejection (ABMR). We conducted a multicenter, prospective, randomized, placebo-controlled, double blind clinical trial to evaluate efficacy and safety of intravenous immunoglobulins (IVIG) combined with rituximab (RTX) (EudraCT 2010-023746-67). Patients with transplant glomerulopathy and anti-HLA donor-specific antibodies (DSA) were eligible. Patients with estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73m2 and/or severe interstitial fibrosis/tubular atrophy were excluded. Patients were randomized to receive IVIG (4 doses of 0.5 g/kg) and RTX (375 mg/m2) or a wrapped isovolumetric saline infusion. Primary efficacy variable was the decline of eGFR at one year. Secondary efficacy variables included evolution of proteinuria, renal lesions and DSA at one year. The planned sample size was 25 patients per group. During 2012-2015, twenty-five patients were randomized (13 to the treatment and 12 to the placebo group). The planned patient enrollment was not achieved because of budgetary constraints and slow patient recruitment. There were no differences between the treatment and placebo groups in eGFR decline (-4.2±14.4 vs. -6.6±12.0 mL/min/1.73 m2, p-value=0.475), increase of proteinuria (+0.9±2.1 vs. +0.9±2.1 g/day, p-value=0.378), Banff scores at one year and MFI of the immunodominant DSA. Safety was similar between groups. These data suggest that the combination of IVIG and RTX is not useful in patients displaying transplant glomerulopathy and DSA.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-26T04:21:10.223078-05:
      DOI: 10.1111/ajt.14520
  • Loss of end-differentiated beta-cell phenotype following pancreatic islet
    • Authors: S J Anderson; M G White, S L Armour, R Maheshwari, D Tiniakos, Y D Muller, E Berishvili, T Berney, J AM Shaw
      Abstract: Replacement of pancreatic β-cells through deceased donor islet transplantation is a proven therapy for preventing recurrent life-threatening hypoglycemia in type 1 diabetes. Although near-normal glucose levels and insulin independence can be maintained for many years following successful islet transplantation, restoration of normal functional β-cell mass has remained elusive. It has recently been proposed that dedifferentiation / plasticity towards other endocrine phenotypes may play an important role in stress-induced β-cell dysfunction in type 2 diabetes. Here we report loss of end-differentiated β-cell phenotype in two intraportal islet allotransplant recipients. Despite excellent graft function and sustained insulin independence, all examined insulin-positive cells had lost expression of the end-differentiation marker, urocortin-3, or appeared to co-express the α-cell marker, glucagon. In contrast, no insulin+ / urocortin-3- cells were seen in non-diabetic deceased donor control pancreatic islets. Loss of end-differentiated phenotype may facilitate β-cell survival during the stresses associated with islet isolation and culture, in addition to sustained hypoxia following engraftment. As further refinements in islet isolation and culture are made in parallel with exploration of alternative β-cell sources, graft sites and ultimately fully-vascularised bioengineered insulin-secreting microtissues, differentiation status immunostaining provides a novel tool to assess whether fully mature β-cell phenotype has been maintained.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-26T04:21:02.971414-05:
      DOI: 10.1111/ajt.14521
  • Erratum
    • PubDate: 2017-09-23T10:30:21.11202-05:0
      DOI: 10.1111/ajt.14501
  • Neuro-immune Interactions in Inflammation and Host Defense: Implications
           for Transplantation
    • Authors: Sangeeta S. Chavan; Pingchuan Ma, Isaac M. Chiu
      Abstract: Sensory and autonomic neurons of the peripheral nervous system (PNS) play a critical role in regulating the immune system during tissue inflammation and host defense. Recent studies have identified the molecular mechanisms underlying the bidirectional communication between the nervous system and the immune system. Here, we highlight the studies that demonstrate the importance of the neuro-immune interactions in health and disease. Nociceptor sensory neurons detect immune mediators to produce pain, and release neuropeptides that act on the immune system to regulate inflammation. In parallel, neural reflex circuits including the vagus nerve-based inflammatory reflex are physiological regulators of inflammatory responses and cytokine production. In transplantation, neuro-immune communication could significantly impact the processes of host-pathogen defense, organ rejection, and wound healing. Emerging approaches to target the PNS such as bioelectronics could be useful in improving the outcome of transplantation. Therefore, understanding how the nervous system shapes the immune response could have important therapeutic ramifications for transplantation medicine.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-23T09:20:34.523096-05:
      DOI: 10.1111/ajt.14515
  • Voriconazole in lung transplant recipients – how worried should we
    • Authors: Hrishikesh S. Kulkarni; Chad A. Witt
      Abstract: Invasive aspergillosis (IA) is the most common invasive mold infection in solid organ transplant (SOT) recipients, occurring in 1-15% of recipients, with a 12-week mortality rate of 20-60%.1 Lung transplant (LTx) recipients are at the highest risk for IA among all SOT recipients, ranging from ulcerative tracheobronchitis, anastomotic site involvement and airway wall necrosis, to pneumonia, mediastinitis, empyema and disseminated fungemia. Additionally, Aspergillus colonization is an independent risk factor for chronic lung allograft dysfunction. Resultingly, a majority of LTx programs now use antifungal prophylaxis against Aspergillus.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-23T09:20:23.835169-05:
      DOI: 10.1111/ajt.14517
  • Donor derived Kaposi's sarcoma in a liver-kidney transplant recipient
    • Authors: S. C. Dollard; D. Douglas, S.V. Basavaraju, D. S. Schmid, M. Kuehnert, B. Aqel
      Abstract: Human herpes virus 8 (HHV-8), also known as Kaposi's sarcoma associated herpesvirus (KSHV), is an oncogenic virus that can cause Kaposi's sarcoma (KS). KS can develop following organ transplantation through reactivation of the recipient's latent HHV-8 infection, or less commonly through donor-derived infection which has higher risk for severe illness and mortality. We describe a case of probable donor-derived KS in the recipient of a liver-kidney transplant. The donor had multiple risk factors for HHV-8 infection. The KS was successfully treated by switching immunosuppression from tacrolimus to sirolimus. With an increasing number of human immunodeficiency virus (HIV)-positive persons seeking organ transplantation and serving as organ donors for HIV-positive recipients, HHV-8 prevalence among donors and recipients will likely increase and with that the risk for post-transplant KS. Pre-determination of HHV-8 status can be useful when considering organ donors and recipients with risk factors, although there are currently no validated commercial tests for HHV-8 antibody screening.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-23T09:20:22.743206-05:
      DOI: 10.1111/ajt.14516
  • Purity of islet preparations and 5-year metabolic outcome of allogenic
           islet transplantation
    • Authors: K Benomar; M Chetboun, S Espiard, A Jannin, K Le Mapihan, V Gmyr, R Caiazzo, F Torres, V Raverdy, C Bonner, D'Herbomez, P Pigny, C Noel, J Kerr-Conte, F Pattou, M C Vantyghem
      Abstract: In allogenic islet transplantation (IT), high purity of islet preparations and low contamination by non-islet cells are generally favored. The aim of the present study was to analyze the relation between the purity of transplanted preparations, and graft function during 5 years post-IT. Twenty-four type 1 diabetic patients, followed-up 5 years after IT, were enrolled. Metabolic parameters and daily insulin requirements were compared between patients who received islet preparations with a mean purity < 50% (LOW purity) or ≥50% (HIGH purity). We also analyzed blood levels of carbohydrate 19-9 (CA 19-9) - a biomarker of pancreatic ductal cells - and glucagon, before and after IT. At 5 years, mean HbA1c levels (p=0.01) and daily insulin requirements (p=0.03) were lower in the LOW purity group. Insulin independence was more frequent in the LOW purity group (p
      PubDate: 2017-09-23T09:15:22.757482-05:
      DOI: 10.1111/ajt.14514
  • A Critical Role for Donor-Derived IL-22 in Cutaneous Chronic GVHD
    • Authors: Kate H. Gartlan; Hemamalini Bommiasamy, Katelyn Paz, Andrew N. Wilkinson, Mary Owen, Dawn K. Reichenbach, Tatjana Banovic, Kimberly Wehner, Faith Buchanan, Antiopi Varelias, Rachel D. Kuns, Karshing Chang, Yuri Fedoriw, Thomas Shea, James Coghill, Michael Zaiken, Maximilian W. Plank, Paul S. Foster, Andrew D. Clouston, Bruce R. Blazar, Jonathan S. Serody, Geoffrey R. Hill
      Abstract: Graft-versus-host disease (GVHD) is the major cause of non-relapse morbidity and mortality after allogeneic stem cell transplant (allo-SCT). Prevention and treatment of GVHD remains inadequate and commonly leads to end-organ dysfunction and opportunistic infection. The role of IL-17 and IL-22 in GVHD remains uncertain, due to an apparent lack of lineage fidelity and variable and contextually determined protective and pathogenic effects. We demonstrate that donor T-cell-derived IL-22 significantly exacerbates cutaneous chronic GVHD, and that IL-22 is produced by highly inflammatory donor CD4+ T-cells post-transplant. IL-22 and IL-17A derive from both independent and overlapping lineages, defined as Th22 and IL-22+Th17 cells. Donor Th22 and IL-22+Th17 share a similar IL-6-dependent developmental pathway and whilst Th22 arise independently of the IL-22+Th17 lineage, IL-17 signaling to donor Th22 directly promotes their development in allo-SCT. Importantly, while both IL-22 and IL-17 mediate skin GVHD, Th17-induced chronic GVHD can be attenuated by IL-22 inhibition in preclinical systems. In the clinic, high levels of both IL-17A and IL-22 expression are present in the skin of GVHD patients after allo-SCT. Together, these data demonstrate a key role for donor-derived IL-22 in chronic skin GVHD and confirm parallel but symbiotic developmental pathways of Th22 and Th17 differentiation.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-23T09:10:29.008773-05:
      DOI: 10.1111/ajt.14513
  • Defining a microRNA-mRNA interaction map for calcineurin inhibitor induced
    • Authors: Christopher J. Benway; John Iacomini
      Abstract: Calcineurin inhibitors induce nephrotoxicity through poorly understood mechanisms thereby limiting their use in transplantation and other diseases. Here we define a microRNA (miRNA)-messenger RNA (mRNA) interaction map that facilitates exploration into the role of miRNAs in cyclosporine-induced nephrotoxicity (CIN) and the gene pathways they regulate. Using photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP), we isolated RNAs associated with Argonaute 2 in the RNA-Induced Silencing Complex (RISC) of cyclosporine A (CsA) treated and control human proximal tubule cells and identified mRNAs undergoing active targeting by miRNAs. CsA causes specific changes in miRNAs and mRNAs associated with RISC, thereby altering post-transcription regulation of gene expression. Pathway enrichment analysis identified canonical pathways regulated by miRNAs specifically following CsA treatment. RNA-seq performed on total RNA indicated that only a fraction of total miRNAs and mRNAs are actively targeted in the RISC indicating that PAR-CLIP more accurately defines meaningful targeting interactions. Our data also revealed a role for miRNAs in calcineurin-independent regulation of JNK and p38 MAPKs caused by targeting of MAP3K1. Together, our data provide a novel resource and unique insights into molecular pathways regulated by miRNAs in CIN. The gene pathways and miRNAs defined may represent novel targets to reduce calcineurin induced nephrotoxicity.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-19T05:05:52.421741-05:
      DOI: 10.1111/ajt.14503
  • Lower Tacrolimus Exposure and Time in Therapeutic Range Increase the Risk
           of De Novo Donor-Specific Antibodies in the First Year of Kidney
    • Authors: Scott Davis; Jane Gralla, Patrick Klem, Suhong Tong, Gina Wedermyer, Brian Freed, Alexander Wiseman, James E. Cooper
      Abstract: De novo donor-specific antibodies (dnDSA) have been associated with reduced graft survival. Tacrolimus (TAC)-based regimens are the most common immunosuppression used in in clinical practice today, yet an optimal therapeutic dose to prevent dnDSA has not been established. We evaluated mean TAC C0 and TAC time in therapeutic range for the risk of dnDSA in a cohort of 538 patients in the first year of kidney transplant. A mean TAC C0 < 8 ng/ml was associated with dnDSA by 6 months (OR 2.51, 95% CI 1.32-4.79, p=0.005) and by 12 months (OR 2.32, 95% CI 1.30-4.15, p=0.004) and there was a graded increase in risk with lower mean TAC C0. TAC time in therapeutic range of < 60% was associated with dnDSA (OR 2.05, 95% CI 1.28-3.30, p=0.003) and acute rejection (HR 4.18, 95% CI 2.31-7.58, p
      PubDate: 2017-09-19T05:05:18.233541-05:
      DOI: 10.1111/ajt.14504
  • The Dangers of Oversimplification – Quality Metrics and Lung
    • Authors: Victor van Berkel
      Abstract: While many aspects of medical care are learning how to cope with the sudden proliferation of publicly reported quality metrics[1], the transplant community has been interpreting this type of data for over thirty years. Under the National Organ Transplantation Act of 1984, transplant centers are required to report their candidate and recipient information to the Organ Procurement and Transplantation Network (OPTN), and that data is then analyzed by the Scientific Registry of Transplant Recipients (SRTR), with outcomes reported on a twice yearly basis on a public website ( article is protected by copyright. All rights reserved.
      PubDate: 2017-09-19T04:35:17.490519-05:
      DOI: 10.1111/ajt.14505
  • A kidney offer acceptance decision tool to inform the decision to accept
           an offer or wait for a better kidney
    • Authors: Andrew Wey; Nicholas Salkowski, Walter K. Kremers, Cory R. Schaffhausen, Bertram L. Kasiske, Ajay K. Israni, Jon J. Snyder
      Abstract: We developed a kidney offer acceptance decision tool to predict the probability of graft survival and patient survival for first-time kidney-alone candidates after an offer is accepted or declined, and we characterized the effect of restricting the donor pool with a maximum acceptable kidney donor profile index (KDPI). For accepted offers, Cox proportional hazards models estimated these probabilities using transplanted kidneys. For declined offers, these probabilities were estimated by considering the experience of similar candidates who declined offers and the probability that declining would lead to these outcomes. We randomly selected 5000 declined offers and estimated these probabilities 3 years post-offer had the offers been accepted or declined. Predicted outcomes for declined offers were well calibrated (< 3% error) with good predictive accuracy (AUC: graft survival, 0.69; patient survival, 0.69). Had the offers been accepted, the probabilities of graft survival and patient survival were typically higher. However, these advantages attenuated or disappeared with higher KDPI, candidate priority, and local donor supply. Donor pool restrictions were associated with worse 3-year outcomes, especially for candidates with high allocation priority. The kidney offer acceptance decision tool could inform offer acceptance by characterizing the potential risk-benefit tradeoff associated with accepting or declining an offer.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-19T04:10:57.52875-05:0
      DOI: 10.1111/ajt.14506
  • Decreasing incidence of cancer after liver transplantation – A Nordic
           population-based study over three decades
    • Authors: A Nordin; F Åberg, E Pukkala, C R Pedersen, H H Storm, A Rasmussen, W Bennet, M Olausson, H Wilczek, B-G Ericzon, S Tretli, P-D Line, T H Karlsen, K M Boberg, H Isoniemi
      Abstract: Cancer remains one of the most serious long-term complications after liver transplantation (LT). Data for all adult LT patients between 1982 and 2013 was extracted from the Nordic Liver Transplant Registry. Through linkage with respective national cancer-registry data, we calculated standardized incidence ratios (SIRs) based on country, sex, calendar time, and age-specific incidence rates. Altogether 461 cancers were observed in 424 individuals out the 4246 LT patients during a mean 6.6-year follow-up. The overall SIR was 2.22 (95%CI 2.02-2.43). SIRs were especially increased for colorectal cancer in recipients with PSC (4.04) and for lung cancer in recipients with alcoholic liver disease (4.96). A decrease in the SIR for cancers occurring within 10 years post-LT was observed from the 1980s: 4.53 (95%CI 2.47-7.60), the 1990s: 3.17 (95%CI 2.70-3.71), to the 2000s: 1.76 (95%CI 1.51-2.05). This was observed across age- and indication-groups. The sequential decrease for the SIR of non-Hodgkin lymphoma was 25.0 - 12.9 - 7.53, and for non-melanoma skin cancer 80.0 - 29.7 - 10.4. Cancer risk after LT was found to be decreasing over time, especially for those cancers that are strongly associated with immunosuppression. Whether immunosuppression minimization contributed to this decrease merits further study.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-19T04:05:22.126902-05:
      DOI: 10.1111/ajt.14507
  • Face/On: Face Transplants and the Ethics of the Other, by Sharrona Pearl
    • Authors: Danielle Paciulli
      Abstract: At its core, a face defines who we are to ourselves and how we relate to others. Faces play a crucial role on interpersonal communication impacting how we know, understand, and believe people, and how we interact with one another. In this sense, it is sometimes hard to really “look” at people beyond their faces. Face/On: Face Transplants and the Ethics of the Other (2017) is an intriguing book written by scholar and writer Dr. Sharrona Pearl. An expert on physiognomy, Pearl delves into the multiple ethical and social dimensions of face transplants touching on questions of self-identity, and peer and social identification.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-12T20:10:30.447411-05:
      DOI: 10.1111/ajt.14496
  • Voriconazole and squamous cell carcinoma after lung transplantation: a
           multicenter study
    • Authors: B. Hamandi; C. Fegbeutel, F. P. Silveira, E. A. Verschuuren, M. Younus, J. Mo, J. Yan, P. Ussetti, P. V. Chin-Hong, A. Solé, C. L. Holmes-Liew, E. M. Billaud, P. A. Grossi, O. Manuel, D. J. Levine, R. G. Barbers, D. Hadjiliadis, J. Aram, L. G. Singer, S. Husain
      Abstract: This study evaluated the independent contribution of voriconazole to the development of squamous cell carcinoma (SCC) in lung transplant recipients, by attempting to account for important confounding factors, particularly immunosuppression.This international, multicenter, retrospective, cohort study included adult patients who underwent lung transplant during 2005-2008. Cox regression analysis was used to assess the effects of voriconazole and other azoles, analyzed as time-dependent variables, on the risk of developing biopsy-confirmed SCC.Nine hundred lung transplant recipients were included. Median follow-up time from transplant to end of follow-up was 3.51 years. In a Cox regression model, exposure to voriconazole alone (adjusted hazard ratio 2.39, 95% confidence interval 1.31-4.37) and exposure to voriconazole and other azole(s) (adjusted hazard ratio 3.45, 95% confidence interval 1.07-11.06) were associated with SCC compared with those unexposed after controlling for important confounders including immunosuppressants.Exposure to voriconazole was associated with increased risk of SCC of the skin in lung transplant recipients. Residual confounding could not be ruled out because of the use of proxy variables to control for some confounders. Benefits of voriconazole use when prescribed to lung transplant recipients should be carefully weighed versus the potential risk of SCC.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-12T10:50:31.559756-05:
      DOI: 10.1111/ajt.14500
  • Maximizing donor allocation: a review of UNOS region 9 donor heart
    • Authors: Donna Mancini; Daniel Goldstein, Samantha Taylor, Leway Chen, Alan Gass, Samantha DeLair, Sean Pinney
      Abstract: This study was performed to determine if organ selection practices for heart utilization by Region 9 transplant programs were optimal, and to identify opportunities to increase local organ recovery. A retrospective review of de-identified region-wide donor data 1/1/10-12/31/13 was performed. Over the study period 537 heart donors were identified, of which 321 (60%) were transplanted. 216 consented hearts were not used; 190 of these were not recovered, and 26 were recovered but not transplanted. 245/321 (76%) hearts were transplanted at one of 5 regional programs, 15 (5%) were transplanted out of region as primary offers, and 61 (19%) were turned down in region and exported. Of the 61 exported hearts, 43 were turned down in region for donor-related “quality” codes (UNOS 830, 833-37) by at least 1 program, the remaining 18 hearts were turned down for non-”quality” reasons, primarily histocompatibility and size. Only 5/43 exported were turned down for “quality” reasons by all regional programs offered the organ. A review of consented, not recovered donor offers suggested an additional 28 organs were possibly appropriate for transplant. Our review of regional turn-downs suggests transplant centers could potentially identify additional usable organs without compromising short term outcomes.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-12T10:25:32.384363-05:
      DOI: 10.1111/ajt.14499
  • Post-transplant oxygen inhalation improves the outcome of subcutaneous
           islet transplantation: a promising clinical alternative to the
           conventional intrahepatic site
    • Authors: H. Komatsu; J. Rawson, A. Barriga, N. Gonzalez, D. Mendez, J. Li, K. Omori, F. Kandeel, Y. Mullen
      Abstract: Subcutaneous tissue is a promising site for islet transplantation, due to its large area and accessibility, which allows minimally invasive procedures for transplantation, graft monitoring, and removal of malignancies as needed. However, relative to the conventional intrahepatic transplantation site, the subcutaneous site requires a large number of islets to achieve engraftment success and diabetes reversal, due to hypoxia and low vascularity. We report that the efficiency of subcutaneous islet transplantation in a Lewis rat model is significantly improved by treating recipients with inhaled 50% oxygen, in conjunction with prevascularization of the graft bed by agarose-bFGF. Administration of 50% oxygen increased oxygen tension in the subcutaneous site to 140 mmHg, compared to 45 mmHg under ambient air. In vitro, islets cultured under 140 mmHg oxygen showed reduced central necrosis and increased insulin release, compared to those maintained in 45 mmHg oxygen. Six hundred syngeneic islets subcutaneously transplanted into the prevascularized graft bed reversed diabetes when combined with post-operative 50% oxygen inhalation for 3 days, a number comparable to that required for intrahepatic transplantation; in the absence of oxygen treatment, diabetes was not reversed. Thus, we show oxygen inhalation to be a simple and promising approach to successfully establishing subcutaneous islet transplantation.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-12T09:15:52.468448-05:
      DOI: 10.1111/ajt.14497
  • Taking the Challenge: A Protocolized Approach to Optimize Pneumocystis
           Pneumonia Prophylaxis in Renal Transplant Recipients
    • Authors: K. F Urbancic; F Ierino, E Phillips, P. F Mount, A Mahony, J. A Trubiano
      Abstract: While trimethoprim-sulfamethoxazole is considered first-line therapy for Pneumocystis pneumonia prevention in renal transplant recipients, reported adverse drug reactions may limit use and increase reliance on costly and less effective alternatives, often aerosolized pentamidine. We report our experience implementing a protocolized approach to trimethoprim-sulfamethoxazole adverse drug reaction assessment and rechallenge to optimize prophylaxis in this patient cohort. We retrospectively reviewed 119 patients receiving Pneumocystis pneumonia prophylaxis prior to and after protocol implementation. Forty-two patients (35%) had 48 trimethoprim-sulfamethoxazole adverse drug reactions documented either at baseline or during the prophylaxis period, of which 83% were non-immune-mediated and 17% were immune-mediated. Significantly more patients underwent trimethoprim-sulfamethoxazole rechallenge after protocol implementation (4/22 vs. 23/27; P=0.0001), with no recurrence of adverse drug reactions in 74%. In those who experienced a new or recurrent reaction (26%), all were mild and self-limiting with only 1 recurrence of an immune-mediated reaction. After protocol implementation, aerosolized pentamidine-associated costs were reduced. The introduction of a standard approach to trimethoprim-sulfamethoxazole rechallenge in the context of both prior immune and non-immune-mediated reactions was safe and successful in improving the uptake of first-line Pneumocystis pneumonia prophylaxis in renal transplant recipients.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-12T09:15:29.955513-05:
      DOI: 10.1111/ajt.14498
  • Integrating kidney transplantation into value-based care for people with
           renal failure
    • Authors: Benjamin E. Hippen; Franklin W. Maddux
      Abstract: Healthcare reimbursement is increasingly tied to value instead of volume, with special attention paid to resource-intensive populations such as patients with renal disease. To this end, Medicare has sponsored pilot projects to encourage providers to develop care coordination and population health management strategies to provide quality care while reducing resource utilization. In this Personal Viewpoint essay, we argue in favor of expanding one such pilot project—the Comprehensive ESRD Care (CEC) initiative—to include patients with advanced chronic kidney disease and kidney transplant recipients. The implementation of the Medicare Access and CHIP Reauthorization Act (MACRA) offers a time-sensitive incentive for transplant centers in particular to align with extant CECs. An “expanded” CEC model proffers opportunity for robust cooperation between general nephrology practices, dialysis providers, and transplant centers to develop care coordination strategies for all patients with renal disease, realign incentives for all clinical stakeholders to increase kidney transplantation rates, and reduce total costs of care.
      PubDate: 2017-09-12T08:00:30.779147-05:
      DOI: 10.1111/ajt.14454
  • Direct acting antiviral agents-based regimen for HCV recurrence after
           combined liver-kidney transplantation: results from the ANRS CO23 CUPILT
    • Authors: Sébastien Dharancy; Audrey Coilly, Claire Fougerou-Leurent, Christophe Duvoux, Nassim Kamar, Vincent Leroy, Albert Tran, Pauline Houssel-Debry, Valérie Canva, Christophe Moreno, Filoména Conti, Jérome Dumortier, Vincent Di Martino, Sylvie Radenne, Victor De Ledinghen, Louis D'Alteroche, Christine Silvain, Camille Besch, Philippe Perré, Danielle Botta-Fridlund, Claire Francoz, François Habersetzer, Hélène Montialoux, Armand Abergel, Maryline Debette-Gratien, Alexandra Rohel, Emilie Rossignol, Didier Samuel, Jean-Charles Duclos-Vallée, Georges-Philippe Pageaux,
      Abstract: HCV infection is associated with reduced patient survival following combined liver-kidney transplantation (LKT). The aim of this study was to assess the efficacy and safety of second generation direct active antiviral (DAAs) in this difficult-to-treat population. The ANRS CO23 CUPILT study is a prospective cohort including transplant recipients with recurrent HCV treated with DAAs. The present work focused on recipients with recurrent HCV following LKT. The study population included 23 patients. All patients received at least one NS5B inhibitor (Sofosbuvir) in their antiviral regimen an average of 90 months after LKT. Ninety six percent of recipients achieved a SVR at week 12 (SVR12). In terms of tolerance, 39% of recipients presented with at least one serious adverse event. None of the patients experienced acute rejection during therapy and there were no deaths during follow-up. The glomerular filtration rate (GFR) decreased significantly from baseline to the end of therapy. However, this study did not show that the decline in GFR persisted over time or that it was directly related to DAAs. The DAAs-based-regimen is well tolerated with excellent results in terms of efficacy. It will become the gold standard for the treatment of recurrent HCV following LKT.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-12T07:10:28.039134-05:
      DOI: 10.1111/ajt.14490
  • Overcoming Pre-existing Alloantibody in Renal Transplantation –
           improving outcomes while reducing need and cost
    • Authors: A. Bentall; Solomon Shlomo J Cohney
      Abstract: In this week's journal, Axelrod and colleagues examine costs incurred by various US centers undertaking Incompatible Live-Donor Kidney Transplantation (ILDKT) – living donor renal transplantation in the presence of preformed antibody (ies) directed against donor HLA (DSAb) [1]. As expected, cost increased as the immunological barrier intensified (as defined by solid phase and cell based assays). While certain aspects of cost recovery are specific to US health care, effectively managing humoral allo-immunity is important to all transplant clinicians, with little progress despite nearly 2 decades of ILDKT [2, 3].This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-11T03:50:34.163742-05:
      DOI: 10.1111/ajt.14494
  • The Impact of Repeated Mismatches in Kidney Transplantations Performed
           After Non-Renal Solid Organ Transplantation
    • Authors: J M Côté; X Zhang, M Dahhou, R Sapir-Picchadze, B Foster, H Cardinal
      Abstract: The aim of this study was to determine whether kidney transplantations performed after previous non-renal solid organ transplants are associated with worse graft survival when there are repeated HLA mismatches (RMM) with the previous donor(s). We performed a retrospective cohort study using data from the Scientific Registry of Transplant Recipients. Our cohort comprised 6, 624 kidney transplantations performed between January 1st 1990 and January 1st, 2015. All patients had previously received one or more non-renal solid organ transplants. RMM were observed in 35.3% of kidney transplantations and 3, 012 grafts were lost over a median follow-up of 5.4 years. In multivariate Cox regression analyses, we found no association between overall graft survival and either RMM in class 1 (hazard ratio (HR): 0.97, 95% confidence interval (CI) 0.89-1.07) or class 2 (HR: 0.95, 95% CI 0.85- 1.06). Results were similar for the associations between RMM, death-censored graft survival and patient survival. Our results suggest that the presence of RMM with previous donor(s) does not have an important impact on allograft survival in kidney transplant recipients who have previously received a non-renal solid organ transplant.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-11T02:30:43.962093-05:
      DOI: 10.1111/ajt.14495
  • A Helpful Approach to Organ Donation: From End-of-Life Care to Effective
           Organ Transplantation
    • Authors: F Caballero; M Puig, J Leal, O Trejo, I Díaz, S Herrera, M Turbau, J Ris, S Benito
      Abstract: We read with interest the report by Witjes et al regarding the influence of end-of-life care on organ donor potential (1). The report promotes innovation in management of potential organ donors outside the ICU, particularly in patients admitted to the emergency department (ED) with acute devastating brain injury (DBI) and imminent brain death.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-11T02:25:18.124559-05:
      DOI: 10.1111/ajt.14493
  • Patient-reported health outcomes in long-term lung transplant survivors: a
           prospective cohort study
    • Authors: A Shahabeddin Parizi; P F M Krabbe, E A M Verschuuren, R A S Hoek, J M Kwakkel-van Erp, M E Erasmus, W der Bij, K M Vermeulen
      Abstract: During the last 3 decades lung transplantation (LTx) has become a proven modality to increase both survival and health-related quality of life (HRQoL) in patients with various end-stage lung diseases. Most previous studies have reported improved HRQoL shortly after LTx. With regard to long-term effects on HRQoL, however, the evidence is less solid. This prospective cohort study was started with 828 patients who were on the waiting list for LTx. Then, in a longitudinal follow-up, 370 post-LTx patients were evaluated annually for up to 15 years. For all wait-listed and follow-up patients, four HRQoL instruments were administered: State-Trait Anxiety Inventory, Zung Self-rating Depression Scale, Nottingham Health Profile, and a visual analogue scale. Cross-sectional and generalized estimating equations (GEE) analysis for repeated measures were performed to assess changes in HRQoL during follow-up. After LTx, patients showed improvement in all HRQoL domains except pain, which remained steady throughout the long-term follow-up. The level of anxiety and depressive symptoms decreased significantly and remained constant. In conclusion, this study showed that HRQoL improves after LTx and tends to remain relatively constant for the entire life span.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-10T06:15:25.324746-05:
      DOI: 10.1111/ajt.14492
  • Normothermic Ex Vivo Kidney Perfusion for Graft Quality Assessment Prior
           to Transplantation
    • Authors: J. Morit007A Kaths; Mátyás Hamar, Juan Echeverri, Ivan Linares, Peter Urbanellis, Jun Yu Cen, Sujani Ganesh, Luke S. Dingwell, Paul Yip, Rohan John, Darius Bagli, Istvan Mucsi, Anand Ghanekar, David Grant, Lisa A. Robinson, Markus Selzner
      Abstract: Normothermic ex vivo kidney perfusion (NEVKP) represents a novel approach for graft preservation and functional improvement in kidney transplantation. We investigated whether NEVKP also allows graft quality assessment prior to transplantation. Kidneys from 30kg pigs were recovered in a model of heart-beating donation (HBD) (group A), following 30min of warm ischemia (WI) (group B), or 60min WI (group C) (n=5/group). Following 8hrs of NEVKP, contralateral kidneys were resected, grafts autotransplanted, and pigs followed for 3 days. Following transplantation, renal function measured by peak serum creatinine, differed significantly among groups (p
      PubDate: 2017-09-10T06:15:23.432632-05:
      DOI: 10.1111/ajt.14491
  • Living donor liver transplantation for biliary atresia: An analysis of
    • Authors: Mureo Kasahara; Koji Umeshita, Seisuke Sakamoto, Akinari Fukuda, Hiroyuki Furukawa, Shotaro Sakisaka, Eiji Kobayashi, Eiji Tanaka, Yukihiro Inomata, Seiji Kawasaki, Mitsuo Shimada, Norihiro Kokudo, Hiroto Egawa, Hideki Ohdan, Shinji Uemoto,
      Abstract: Biliary atresia (BA) is the most common indication for liver transplantation (LT) in pediatric population. This study analyzed the comprehensive factors that might influence the outcomes of patients with BA who undergo living donor LT by evaluating the largest cohort with the longest follow-up in the world. Between November 1989 and December 2015, 2,085 BA patients underwent LDLT in Japan. There were 763 male and 1,322 female recipients with a mean age of 5.9 years and body weight of 18.6 kg. The 1-, 5-, 10-, 15-and 20-year graft survival rates for the BA patients undergoing LDLT were 90.5%, 90.4%, 84.6%, 82.0% and 79.9%, respectively. The donor body mass index, ABO incompatibility, graft type, recipient age, center experience and transplant era were found to be significant predictors of the overall graft survival. Adolescent age (12 to
      PubDate: 2017-09-10T06:15:21.301563-05:
      DOI: 10.1111/ajt.14489
  • Liver Transplantation Equity: Supply, Demand, and Access
    • Authors: David Axelrod; Heidi Yeh
      Abstract: Despite advances in treatment for end stage liver disease (ESLD), death from cirrhosis and chronic liver disease remains a major source of morbidity and mortality, particularly in younger patients. The National Center for Health Statistics estimates that the years of life lost prior to age 75 due to ESLD has increased from 164.1 per 100,000 in 2000 to 190.3 in 2015, exceeding life years lost from cerebrovascular disease (161.0), colorectal cancer (123.3), and HIV (50.4).(1) Liver transplantation is the sole treatment for patients with decompensated liver failure, with exceptional success among patients who make it through transplant. Unfortunately, the barriers to transplant are significant, as patients must be referred for transplant evaluation, meet medical and financial eligibility requirements, survive to be allocated one of an insufficient number of donor organs, and maintain their allograft after transplantation. At each step, patients with lower socioeconomic status are known to face greater challenges and have diminished access to transplant.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-09T02:55:22.324314-05:
      DOI: 10.1111/ajt.14488
  • Fate of transplanted lungs is controlled by immune cells encounter within
           pulmonary allografts
    • Authors: Nicolas Degauque
      Abstract: Lung transplantation represents a highly successful therapy for patients with end-stage lung diseases. Nevertheless, compared with other types of solid-organ transplants, the survival rate of lung transplantation is one of the lowest: 50% of patients will lose their graft 5 years after transplantation. A technically challenging mouse model of orthotopic lung transplant has been helpful in unveiling the singularity of the immune response during the course of a lung transplant1.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-09T02:55:20.187247-05:
      DOI: 10.1111/ajt.14487
  • A Novel Patient-Centered “Intention-To-Treat” Metric of U.S. Lung
           Transplant Center Performance
    • Authors: Dawn A. Maldonado; Arindam RoyChoudhury, David J. Lederer
      Abstract: Despite the importance of pre-transplant outcomes, one-year post-transplant survival is typically considered the primary metric of lung transplant center performance in the U.S.. We designed a novel lung transplant center performance metric that incorporates both pre- and post-transplant survival time. We performed an ecologic study of 12,187 lung transplant candidates listed at 56 U.S. lung transplant centers between 2006 and 2012. We calculated an “intention-to-treat” survival (ITTS) metric as the percentage of waiting list candidates surviving at least one year after transplantation. The median center-level 1-year post-transplant survival rate was 84.1%, and the median center-level ITTS was 66.9% (mean absolute difference 19.6%, 95% limits of agreement 4.3 to 35.1%). All but 10 centers had ITTS values that were significantly lower than 1-year post-transplant survival rates. Observed ITTS was significantly lower than expected ITTS for 7 centers. These data show that one-third of lung transplant candidates do not survive one year after transplantation, and that 12% of centers have lower than expected ITTS. An “intention-to-treat survival” metric may provide a more realistic expectation of patient outcomes at transplant centers and may be of value to transplant centers and policymakers.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-01T09:42:24.919425-05:
      DOI: 10.1111/ajt.14486
  • People should not be banned from transplantation only because of their
           country of origin
    • Authors: Alvin E. Roth; Kimberly D. Krawiec, Siegfredo Paloyo, Obi Ekwenna, Christopher L. Marsh, Alexandra J. Wenig, Ty B. Dunn, Michael A. Rees
      Abstract: Previously [1,2], we described how a Filipino husband-and-wife patient–donor pair were included in an American kidney exchange.1,2 Delmonico and Ascher object in the strongest terms.3 They write that ethical Global Kidney Exchange (GKE) with patient–donor pairs from the developing world “is not feasible when the culture is so experienced with organ sales.”This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-01T09:25:21.734958-05:
      DOI: 10.1111/ajt.14485
  • Open dialogue between professionals with different opinions builds the
           best policy
    • Authors: Ignazio Marino; Alvin Roth, Michael Reese, Cataldo Doria
      Abstract: Delmonico and Ascher [1] respond to Rees et al. [2], but also to a confidential letter of intent, a work-in-progress draft for a possible grant application, which is not a public document and was never meant for distribution. We ask how they would respond to their colleagues taking their confidential grant application, making it public by email distribution, and leading an effort to discredit it before it is even written'This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-01T09:21:24.296293-05:
      DOI: 10.1111/ajt.14484
  • Donor-derived Hepatitis C transmission from NAT negative donors - still an
           unexpected event
    • Authors: Cameron R. Wolfe; Marian G. Michaels
      Abstract: We read with interest the meeting report by Levitsky et al.1, detailing the American Society of Transplantation consensus conference on the use of hepatitis C (HCV) viremic donors. We commend the authors of the meeting report for their excellent discussion of HCV risk, and their caution regarding the research frameworks to be used moving forward. We especially applaud their clarification of the key difference between serologically positive donors and those with nucleic acid test (NAT) confirmed viremia.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-01T09:20:11.791412-05:
      DOI: 10.1111/ajt.14483
  • Deceased Donor Uterus Retrieval: A Novel Technique and Workflow
    • Authors: G. Testa; T. Anthony, G. McKenna, E. C. Koon, K. Wallis, G. B. Klintmalm, J. C. Reese, L. Johannesson
      Abstract: Uterus transplantation has proven successful when performed with a living donor. Subsequently, interest in the novel field of reproductive transplantation is growing. The procedure is still considered experimental, with fewer than 25 cases performed worldwide, and the techniques of both uterus procurement and transplantation are still developing. We detail a new approach to deceased donor uterus procurement. In contrast to reported techniques and our own initial experience, in which the deceased donor uterus was procured post cross-clamp and after other organs were procured, our approach now is to perform the uterus procurement prior to the procurement of other organs in a multiorgan donor and hence prior to cross-clamp. We describe our practical experience in developing and implementing the logistical workflow for deceased donor uterus procurement in a deceased multiorgan donor setting.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-31T07:56:13.932548-05:
      DOI: 10.1111/ajt.14476
  • Insights on the impact of diet-mediated microbiota alterations on immunity
           and diseases
    • Authors: Akihito Harusato; Benoit Chassaing
      Abstract: The intestinal tract is inhabited by a large and diverse community of bacteria collectively referred to as the gut microbiota. The intestinal microbiota is composed by 500-1000 distinct species, and alterations in its composition are associated with a variety of diseases including obesity, diabetes, and inflammatory bowel disease (IBD). Importantly, microbiota transplantation from diseased patients or mice (IBD, metabolic syndrome, etc.) to germ-free mice was found to be sufficient to transfer some aspects of disease phenotypes, indicating that altered microbiota is playing a direct role in those particular conditions. Moreover, it is now well admitted that the intestinal microbiota is involved in shaping and maturating the immune system, with for example the observation that germ-free animals harbor a poorly developed intestinal immune system and that some single bacteria species, such as segmented filamentous bacteria (SFB), are sufficient to induce the expansion of Th17 cells (CD4+ T helper cells producing IL-17). We will present herein an overview of the interactions occurring between the intestinal microbiota and the immune system, and we will discuss how a dietary-induced disruption of the intestinal environment may influence transplantation outcomes.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-31T07:55:54.971182-05:
      DOI: 10.1111/ajt.14477
  • Response to: HCV Viremic Donors With Hepatic Bridging Fibrosis: Are We
           Ready To Use Their Livers in The Era of Direct-ActingAntivirals'
    • Authors: J. Levitsky; R. N. Formica
      Abstract: We read with interest the response by Martini et al to our consensus conference and recommendations on the use of hepatitis C viremic organs in negative recipients (1,2). Their case report is certainly provocative in considering fibrotic viremic donors, given the ability to eradicate HCV early and prevent further damage to a more injured graft. As we mentioned in our report, we should see an increase number of HCV-infected baby boomers within the next decade who have more likelihood of hepatic fibrosis compared to the younger, drug-injecting population (3).This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-31T07:55:51.754299-05:
      DOI: 10.1111/ajt.14478
  • Strengths and Weaknesses of using SRTR Data to Shape the Management of the
           HIV infected Kidney Transplant Recipient
    • Authors: Peter G Stock
      Abstract: In this edition of AJT, Sawinski et al examine the impact of combined antiretroviral therapy (cART) on kidney transplant outcomes performed in HIV infected recipients using the Scientific Registry of Transplant Recipients (SRTR) linked to IMS pharmacy refills (1). They found that the use of cART regimens based on protease inhibitors (PI) had a marked detrimental impact on patient and graft survival. The etiology of the surprisingly poorer results in HIV positive recipients on PI based regimens could not be ascertained based on their analysis.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-31T07:55:48.188882-05:
      DOI: 10.1111/ajt.14479
  • CD4+CD28null T Cells Are Not Alloreactive Unless Stimulated by IL-15
    • Authors: B Dedeoglu; N. H. R Litjens, M Klepper, R Kraaijeveld, W Verschoor, C. C Baan, M. G. H Betjes
      Abstract: Proinflammatory, cytotoxic CD4+CD28null T cells can be substantially expanded in patients with end-stage renal disease. These cells have been associated with the risk for rejection, but their alloreactive potential is unknown. CD4+CD28null T cells were stimulated with HLA-mismatched antigen presenting cells in the absence/presence of exogenous cytokines. Alloreactive potential was evaluated by proliferation, degranulation, cytotoxicity and cytokine production. Furthermore, their suppressive capacity was assessed by measuring inhibition of proliferating alloreactive CD28+ T cells. CD4+CD28null T cells contained alloreactive (CD137+) T cells but did not proliferate in response to allogeneic stimulation, unless IL-15 was added. However, they could proliferate upon stimulation with CMV-antigen without exogenous cytokines. IL-15 increased the frequency of proliferating alloreactive CD4+CD28null T cells to 30.5% without inducing CD28 expression (p
      PubDate: 2017-08-31T07:55:39.340183-05:
      DOI: 10.1111/ajt.14480
  • The argument against House Bill 1938
    • Authors: Adnan Sharif
      Abstract: Bruce and Koch cite ethical problems with presumed consent legislation in relation to House Bill 1938 currently under debate by Texan legislators (1). Citing flawed assumptions by proponents of the change, they argue for further empirical research and assessment of the impact of the presumed consent model in the United States. However, a simple look at the recent ‘real world’ experience from Wales switching to presumed consent is sufficient to demonstrate the futility of such a change.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-31T07:55:37.915193-05:
      DOI: 10.1111/ajt.14481
  • Getting to Transplantation
    • Authors: Michael S. Mulvihill; Matthew G. Hartwig
      Abstract: Candidates for lung transplantation (LTX) are increasingly critically-ill at the time of transplantation, and as such more often require invasive support strategies to bridge to transplant (1). Traditionally, this required invasive Mechanical Ventilation (iMV), and today more frequently includes the use of Extra-Corporeal Membrane Oxygenation (ECMO) to achieve adequate gas exchange. While there has been concern regarding futility of transplantation in such critically-ill cohorts due to early experience, post-transplant survival has steadily improved in the highest LAS quartile candidates (2).This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-31T07:55:23.78862-05:0
      DOI: 10.1111/ajt.14482
  • Opposition to Irresponsible Global Kidney Exchange
    • Authors: Francis L. Delmonico; Nancy L. Ascher
      Abstract: We are writing in opposition to the proposed Global Kidney Exchange that would solicit living donors from economically underdeveloped countries such as Mexico, the Philippines, Kenya, India and Ethiopia (1). The experience of representatives from countries such as India and Mexico reported at the Vatican Pontifical Academy of Sciences Summit on the topic of organ trafficking in February, 2017 was very clear—these locations are sites of organ trafficking (2-6). The capacity of this project to assure that targeted donors in underdeveloped countries will be emotionally –related, free of coercion and fully informed of risk, is not feasible when the culture is so experienced with organ sales.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-21T09:05:21.569143-05:
      DOI: 10.1111/ajt.14473
  • Predicted indirectly recognizable HLA epitopes (PIRCHE): only the tip of
           the iceberg'
    • Authors: Gwendaline Guidicelli; Jean-Luc Taupin, Jonathan Visentin
      Abstract: We read with great interest the article by Lachmann et al. studying the value of the predicted indirectly recognizable HLA epitope (PIRCHE-II) score for the prediction of de novo donor-specific antibody (dnDSA) development (1). It follows other publications from E. Spierings’ team tackling the difficult task of identifying which donor-derived HLA allopeptides are presented by recipients’ antigen-presenting cells through class II HLA molecules (2). This is of outstanding importance for alloreactive B-lymphocytes, as this step precedes the interaction with alloreactive CD4+ T-lymphocytes in charge of completing the B-lymphocyte activation process down to dnDSA production.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-21T09:05:20.517128-05:
      DOI: 10.1111/ajt.14474
  • Hospital Readmissions Following HLA-Incompatible Live Donor Kidney
           Transplantation: A Multi-Center Study
    • Authors: Babak J. Orandi; Xun Luo, Elizabeth A. King, Jacqueline M. Garonzik-Wang, Sunjae Bae, Robert A. Montgomery, Mark D. Stegall, Stanley C. Jordan, Jose Oberholzer, Ty B. Dunn, Lloyd E. Ratner, Sandip Kapur, Ronald P. Pelletier, John P. Roberts, Marc L. Melcher, Pooja Singh, Debra L. Sudan, Marc P. Posner, Jose M. El-Amm, Ron Shapiro, Matthew Cooper, George S. Lipkowitz, Michael A. Rees, Christopher L. Marsh, Bashir R. Sankari, David A. Gerber, Paul W. Nelson, Jason Wellen, Adel Bozorgzadeh, A. Osama Gaber, Dorry L. Segev
      Abstract: 30% of kidney transplant recipients are readmitted in the first month post-transplant. Those with donor-specific antibody requiring desensitization and incompatible live donor kidney transplantation (ILDKT) constitute a unique subpopulation that might be at higher readmission risk. Drawing on a 22-center cohort, 379 ILDKTs with Medicare primary insurance were matched to compatible transplant matched controls and to waitlist-only matched controls on panel reactive antibody, age, blood group, renal replacement time, prior kidney transplantation, race, gender, diabetes, and transplant date/waitlisting date. Readmission risk was determined using multilevel, mixed-effects Poisson regression. In the first month, ILDKTs had a 1.28-fold higher readmission risk than compatible controls (95%CI: 1.13-1.46; P
      PubDate: 2017-08-21T09:01:43.888171-05:
      DOI: 10.1111/ajt.14472
  • Utility of Protocol Kidney Biopsies for De Novo Donor Specific Antibodies
    • Authors: Sandesh Parajuli; Patrick K. Reville, Thomas M. Ellis, Arjang Djamali, Didier A. Mandelbrot
      Abstract: There is limited information about the role of protocol kidney biopsies for de novo donor specific antibodies (dnDSA) in kidney transplant recipients, especially in those with stable graft function. We initiated a routine post-transplant DSA monitoring and surveillance biopsy program for dnDSA since 2014. We identified 45 kidney transplant recipients with dnDSA detected between January 2014 and February 2017 that underwent kidney biopsy within 60 days of detection of dnDSA. 29 (64%) had stable graft function and 16 (36%) had impaired graft function at the time of dnDSA detection. Even in the group with stable graft function, we found a high rate of rejection (53%), on biopsy. 88% of patients with impaired graft function had rejection. Those patients with impaired graft function had significantly lower eGFR at 12 months post biopsy and at last follow up. Those with impaired graft function had more graft failures; however, this result was not statistically significant. The high rate of asymptomatic rejection, and the fact that outcomes in asymptomatic patients are poor, is in support of the utility of surveillance biopsies in patients with dnDSA.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-14T04:50:57.592009-05:
      DOI: 10.1111/ajt.14466
  • Deletion of the Activating NK Cell Receptor NKG2D Accelerates Rejection of
           Cardiac Allografts
    • Authors: Cornelia Fabritius; Paul Viktor Ritschl, Thomas Resch, Mario Roth, Susanne Ebner, Julia Günther, Vanessa Mellitzer, Anh-Vu Nguyen, Johann Pratschke, Martina Sauter, Karin Klingel, Katja Kotsch
      Abstract: It has already been shown that neutralization of the activating NK cell receptor NKG2D in combination with co-stimulation blockade prolongs graft survival of vascularized transplants. In order to clarify the underlying cellular mechanisms, we transplanted complete MHC-disparate BALB/c-derived cardiac grafts into C57BL/6 wildtypes or mice deficient for NKG2D (Klrk1-/-). Although median survival was eight days for both recipient groups, we detected already at day 5 post-transplantation significantly greater intragraft frequencies of NKp46+ NK cells in Klrk1-/- recipients than in wildtypes. This was followed by a significantly greater infiltration of CD4+, but a lesser infiltration of CD8+ T cell frequencies. Contrary to published observations, co-stimulation blockade with CTLA4-Ig resulted in a significant acceleration of cardiac rejection by Klrk1-/- recipients, and this result was confirmed by applying a neutralizing antibody against NKG2D to wildtypes. In both experimental set-ups,grafts derived from Klrk1-/- recipients were characterized by significantly higher levels of IFNγ mRNA and both CD4+ and CD8+ T cells displayed a greater capacity for degranulation and IFNγ production. In summary, our results clearly illustrate that NKG2D expression in the recipient is important for cardiac allograft survival, thus supporting the hypothesis that impairment of NK cells prevents the establishment of graft acceptance.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-14T04:50:56.052912-05:
      DOI: 10.1111/ajt.14467
  • Harms of Unsuccessful Donation After Circulatory Death: An Exploratory
    • Authors: Lauren J Taylor; Anne Buffington, Joseph R Scalea, Norman Fost, Kenneth D Croes, Joshua D Mezrich, Margaret L Schwarze
      Abstract: While donation after circulatory death (DCD) has expanded options for organ donation, many who wish to donate are still unable to do so. We conducted face-to-face interviews with family members (n=15) who had direct experience with unsuccessful DCD and five focus groups with professionals involved in the donation process. We used qualitative content analysis to characterize harms of non-donation as perceived by participants. Participants reported a broad spectrum of harms impacting organ recipients, donors and donor families. Harms included waste of precious life-giving organs and hospital resources, inability to honor the donor's memory and character, and impaired ability for families to make sense of tragedy and cope with loss. Donor families empathized with the initial hope and ultimate despair of potential recipients who must continue their wait on the transplant list. Focus group members reinforced these findings and highlighted the struggle of families to navigate the uncertainty regarding the timing of death during the donation process. While families reported significant harm, many appreciated the donation attempt. These findings highlight the importance of organ donation to donor families and the difficult experiences associated with current processes that could inform development of alternative donation strategies.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-14T04:45:41.770664-05:
      DOI: 10.1111/ajt.14464
  • Incidence and outcomes of primary central nervous system lymphoma in solid
           organ transplant recipients
    • Authors: Parag Mahale; Meredith S. Shiels, Charles F. Lynch, Eric A. Engels
      Abstract: Primary central nervous system lymphoma (PCNSL) risk is greatly increased in immunosuppressed HIV-infected people. Using data from the United States transplant registry linked with 17 cancer registries (1987-2014), we studied PCNSL and systemic non-Hodgkin lymphoma (NHL) in 288,029 solid organ transplant recipients. Transplant recipients had elevated incidence for PCNSL compared with the general population (standardized incidence ratio=65.1; N=168), and this elevation was stronger than for systemic NHL (standardized incidence ratio=11.5; N=2,043). Compared to kidney recipients, PCNSL incidence was lower in liver recipients (adjusted incidence rate ratio [aIRR]=0.52), similar in heart and/or lung recipients, and higher in other/multiple organ recipients (aIRR=2.45). PCNSL incidence was higher in Asians/Pacific Islanders than non-Hispanic whites (aIRR=2.09); after induction immunosuppression with alemtuzumab (aIRR=3.12), monoclonal antibodies (aIRR=1.83), or polyclonal antibodies (aIRR=2.03); in recipients who were Epstein-Barr virus-seronegative at the time of transplant and at risk of primary infection (aIRR=1.95); and within the first 1.5 years after transplant (aIRR>2.00). Compared to other recipients, those with PCNSL had increased risk of death (adjusted hazard ratio [aHR]=11.79) or graft failure/retransplantation (aHR=3.24). Recipients with PCNSL also had higher mortality than those with systemic NHL (aHR=1.48). In conclusion, PCNSL risk is highly elevated among transplant recipients, and it carries a poor prognosis.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-14T04:45:21.572117-05:
      DOI: 10.1111/ajt.14465
  • Laparoscopic Sleeve Gastrectomy Improves Renal Transplant Candidacy and
           Post-Transplant Outcomes in Morbidly Obese Patients
    • Authors: Y. Kim; A.D. Jung, V.K. Dhar, J.S. Tadros, D.P. Schauer, E.P. Smith, D.J. Hanseman, M.C. Cuffy, R.R. Alloway, A.R. Shields, S.A. Shah, E.S. Woodle, T.S. Diwan
      Abstract: Morbid obesity is a barrier to KT due to inferior outcomes, including higher rates of new-onset diabetes after transplantation (NODAT), delayed graft function (DGF), and graft failure. LSG increases transplant eligibility by reducing body mass index (BMI) in KT candidates, but the effect of surgical weight loss on post-transplant outcomes is unknown. Reviewing single-center medical records, we identified all patients who underwent LSG prior to KT from 2011-2016 (n=20). Post-LSG kidney recipients were compared with similar-BMI recipients who did not undergo LSG, using 2:1 direct matching for patient factors. McNemar's test and signed-rank test were used to compare groups. Among post-LSG patients, mean BMI was 41.5±4.4 kg/m2 at initial encounter, which decreased to 32.3±2.9 kg/m2 prior to KT (p
      PubDate: 2017-08-14T04:45:19.685146-05:
      DOI: 10.1111/ajt.14463
  • The Kidney Allocation System Does Not Appropriately Stratify Risk of
           Pediatric Donor Kidneys: Implications for Pediatric Recipients
    • Authors: S.M. Nazarian; A.W. Peng, B. Duggirala, M. Gupta, T. Bittermann, S. Amaral, M.H. Levine
      Abstract: Kidney Allocation System (KAS) was enacted in 2014 to improve graft utility, while facilitating transplantation of highly-sensitized patients and preserving pediatric access to high-quality kidneys. Central to this system is the Kidney Donor Profile Index (KDPI), a metric intended to predict transplant outcomes based on donor characteristics but derived using only adult donors. We posited that KAS had inadvertently altered the profile and quantity of kidneys made available to pediatric recipients. This question arose from our observation that most pediatric donors carry a KDPI over 35 and have therefore been rendered relatively inaccessible to pediatric recipients under KAS. Here we explore early trends in pediatric transplantation following KAS, including 1) use of pediatric donors, 2) use of Public Health System (PHS) high infectious risk donors, 3) wait time, and 4) living donor transplantation. We note some concerning preliminary changes following KAS implementation, including the allocation of fewer deceased donor pediatric kidneys to children and stagnation in pediatric wait times. Moreover, the poor predictive power of the KDPI for adult donors appears to be even worse when applied to pediatric donors. These early trends warrant further observation and consideration of changes in pediatric kidney allocation if they persist.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-14T04:40:25.552855-05:
      DOI: 10.1111/ajt.14462
  • Response to “Minimization of Ischemic Cholangiopathy in Donation after
           Cardiac Death Liver Transplantation: Is it Thrombolytic Therapy or Warm
           Ischemic Time Stringency and Donor Bile Duct Flush'
    • Authors: H. Bohorquez; G E Loss
      Abstract: We thank Giorgakis and colleagues for their interest in our recent published article (1, 2). Since the etiology of ischemic cholangiopathy (IC) in Donation after Cardiac Death (DCD) for Liver Transplantation (LT) is not well defined, hypotheses include ischemia–reperfusion injury, microvascular thrombosis, cytotoxic injury, and impaired biliary epithelial regeneration (3-5), adopting a multifaceted protocol to optimize perioperative conditions is essential. We concur with their observation that fast organ recovery with rapid decompression, in-situ aortic and portal flushing, biliary tree flushing –and in our institution, retrograde venous flushing-, keep short ischemic times, careful donor–recipient selection and pristine technical implantation are imperative to good outcomes.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-12T02:50:23.222358-05:
      DOI: 10.1111/ajt.14460
  • In-situ split liver splitting under extra-corporeal membrane oxygenation
           in brain-dead donor
    • Authors: Assalino Michela; Pietro Majno, Christian Toso, Thierry Berney, Raphaël Giraud, Philipp Dutkowski, Axel Andres, Barbara Wildhaber, Laure Elkrief
      Abstract: Hemodynamic instability is generally considered as a contraindication to liver splitting, in particular when using an in-situ technique. We describe the cases of two young donors with brain death in whom refractory cardiac arrest and hemodynamic instability were supported by veno-arterial extracorporeal membrane oxygenation (VA-ECMO), allowing uneventful in situ splitting. Two adult and two pediatric liver recipients were successfully transplanted with immediate graft function. Favorable outcomes were also observed for the other transplanted organs, including one heart, two lungs and four kidneys. Refractory cardiac arrest and hemodynamic instability corrected by VA-ECMO should not be considered as a contraindication to in-situ liver splitting.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-12T02:50:22.15046-05:0
      DOI: 10.1111/ajt.14461
  • Long- term outcome of renal transplantation from octogenarian donors: A
           multicenter controlled study
    • Authors: Piero Ruggenenti; Cristina Silvestre, Luigino Boschiero, Giovanni Rota, Lucrezia Furian, Annalisa Perna, Giuseppe Rossini, Giuseppe Remuzzi, Paolo Rigotti
      Abstract: To assess whether biopsy-guided selection of kidneys from very old brain-death donors enables more successful transplantations, this multicenter, observational study compared graft survival between 37 Recipients of one or two histologically evaluated kidneys from>80-years-old donors and 198 Reference-Recipients of non-histologically evaluated single grafts from ≤60-year-old donors (transplant period: 2006-2013 at three Italian Centers). Over a median (IQR) of 25 (13-42) months, two Recipients (5.4%) and 10 Reference-Recipients (5.1%) required dialysis [crude and donor age- and sex-adjusted HRs (95% CI): 1.55 (0.34-7.12), p=0.576 and 1.41 (0.10-19.54), p=0.798, respectively]. Shared frailty analyses confirmed similar outcomes in a 1:2 propensity score study comparing Recipients with 74 Reference-Recipients matched by center, year, donor and recipient sex and age. Serum creatinine was similar across groups over 84-month follow-up. Recipients had remarkably shorter waiting times than Reference-Recipients and Matched-Reference-Recipients [7.5 (4.0-19.5) vs 36 (19-56) and 40 (24-56) months, respectively, p
      PubDate: 2017-08-09T07:50:43.156396-05:
      DOI: 10.1111/ajt.14459
  • Exercise capacity in young adults after hematopoietic cell transplantation
           in childhood
    • Authors: Anders Öberg; Margareta Genberg, Andrei Malinovschi, Hans Hedenström, Per Frisk
      Abstract: A symptom-limited incremental cycle ergometer test was performed in 17 young adults treated with hematopoietic cell transplantation and total body irradiation for hematological malignancies during childhood. They were compared with 17 sex- and age-matched healthy controls. Assessments of pulmonary function, cardiac function, body composition and levels of growth hormone were also included. The median follow-up was 17.7 years. Patients achieved 63.2% of the predicted peak workload, whereas controls achieved 96.1% (p80% (p
      PubDate: 2017-08-08T18:01:27.480558-05:
      DOI: 10.1111/ajt.14456
  • The Kidney Allocation System Claims Equity;It Is Time to Review Utility
           and Fairness
    • Authors: G. B. Klintmalm; B. Kaplan
      Abstract: The current kidney allocation system (KAS) implemented by the United Network for Organ Sharing in December 2014 was intended to balance inequities in kidney allocation while increasing utility by transplanting kidneys expected to last the longest in patients expected to live the longest. In its first iteration, termed Life Years from Transplant (LYFT), a fairly simple system of allocation was proposed to allocate kidneys based on this principle. LYFT, as opposed to our current process, also addressed the need to have a codified system to allocate kidneys unsuitable for younger patients to older recipients, such that utility could be maximized across the spectrum of potential recipients. Due to political pressures, LYFT was not instituted and our current KAS was implemented as a compromise solution (1).
      PubDate: 2017-08-08T18:01:21.530438-05:
      DOI: 10.1111/ajt.14457
  • Pure Laparoscopic Living Donor Hepatectomy: Focus on 55 Donors Undergoing
           Right Hepatectomy
    • Authors: K. S. Suh; S. K. Hong, K. W. Lee, N. J. Yi, H. S. Kim, S. W. Ahn, K. C. Yoon, J. Y. Choi, D. Oh, H. Kim
      Abstract: Although laparoscopic donor hepatectomy is increasingly common, few centers with substantial experience have reported the results of pure laparoscopic donor right hepatectomy (PLDRH). Here, we report the experiences of 60 consecutive liver donors undergoing pure laparoscopic donor hepatectomy (PLDH), with most undergoing right hepatectomy. None of the 60 donors who underwent PLDH had intraoperative complications and none required transfusions, reoperation, or conversion to open hepatectomy. Forty-five donors who underwent PLDRH between November 2015 and December 2016 were compared with 42 who underwent conventional donor right hepatectomy (CDRH) between May 2013 and February 2014. The total operation time was longer (330.7 vs. 280.0 minutes; P
      PubDate: 2017-08-08T18:01:14.416063-05:
      DOI: 10.1111/ajt.14455
  • Heparin-binding protein, lysozyme and inflammatory cytokines in
           bronchoalveolar lavage fluid as diagnostic tools for pulmonary infection
           in lung transplanted patients
    • Authors: Anna Stjärne Aspelund; Helena Hammarström, Malin Inghammar, Hillevi Larsson, Lennart Hansson, Bertil Christensson, Lisa I. Påhlman
      Abstract: Pulmonary infection is a common complication after lung transplantation and early detection is crucial for outcome. However, the condition can be clinically difficult to diagnose and to distinguish from rejection. The aim of this prospective study was to evaluate Heparin-binding protein (HBP), lysozyme and the cytokines Interleukin (IL)-1β, IL-6, IL-8, IL-10 and Tumour Necrosis Factor (TNF) in bronchoalveolar lavage fluid (BALF) as potential biomarkers for pulmonary infection in lung transplanted (Lntx) patients.One hundred and thirteen BALF samples from 29 Lntx recipients were collected at routine scheduled bronchoscopies at 3 and 6 months, or on clinical indication. Samples were classified into no, possible, probable or definite infection at the time of sampling. Rejection was defined by biopsy results. HBP, lysozyme and cytokines were analysed in BALF and correlated to likelihood of infection and rejection. All biomarkers were significantly increased in BALF during infection, while patients with rejection presented low levels that were comparable to non-infection samples. HBP, IL-1β and IL-8 were the best diagnostic markers of infection with area under the receiver operating characteristic curve values of 0,88, 0.91 and 0.90 respectively. In conclusion, HBP, IL-1β and IL-8 could be useful diagnostic markers of pulmonary infection in Lntx patients.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-08T18:01:06.496289-05:
      DOI: 10.1111/ajt.14458
  • iNKT cell activation plus T-cell transfer establishes complete chimerism
           in a murine sublethal bone marrow transplant model
    • Authors: Rumi Ishii; Toshihito Hirai, Satoshi Miyairi, Kazuya Omoto, Masayoshi Okumi, Yasuyuki Ishii, Kazunari Tanabe
      Abstract: Transplant tolerance induction makes it possible to preserve functional grafts for a lifetime without immunosuppressants. One powerful method is to generate mixed hematopoietic chimeras in recipients by adoptive transfer of donor-derived bone marrow cells (BMCs). In our murine transplantation model, we established a novel method for mixed chimera generation using sublethal irradiation, CD40-CD40L blockade, and invariant natural killer T-cell activation. However, numerous BMCs that are required to achieve stable chimerism makes it difficult to apply this model for human transplantation. Here, we show that donor-derived splenic T cells could contribute to not only the reduction of BMC usage but also the establishment of complete chimerism in model mice. By cotransfer of T cells together even with one-fourth of the BMCs used in our original method, the recipient mice yielded complete chimerism and could acquire donor-specific skin-allograft tolerance. The complete chimeric mice did not show any remarks of graft versus host reaction in vivo and in vitro. Inhibition of the apoptotic signal resulted in increase in host-derived CD8+ T cells and chimerism brake. These results suggest that donor-derived splenic T cells having veto activity play a role in the depletion of host-derived CD8+ T cells and the facilitation of complete chimerism.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-02T02:06:00.160804-05:
      DOI: 10.1111/ajt.14453
  • Dual-Graft Adult Living Donor Liver Transplantation with ABO-Incompatible
           Graft: Short-term and Long-term Outcomes
    • Authors: J.H. Kwon; G.W. Song, S. Hwang, K. H. Kim, C.S. Ahn, D.B. Moon, T.Y. Ha, D.H. Jung, G.C. Park, S.H. Kim, W.H. Kang, H.D. Cho, E.K. Jwa, E.Y. Tak, V.A. Kirchner, S.G. Lee
      Abstract: ABO-incompatible (ABOi) dual-graft (DG) adult living donor liver transplantation (ALDLT) is not commonly performed due to its inherently intricate surgical technique and immunological complexity. Therefore, data is lacking on the short- and long-term clinical outcomes of ABOi DG ALDLT. We performed a retrospective study by reviewing the medical records of patients who underwent ABOi DG ALDLT between 2008 and 2014. Additionally, computed tomography (CT) volumetric analysis was conducted to assess the graft regeneration rate. The mean age of a total of 28 recipients was 50.2 ± 8.5 years, and the mean model for end-stage liver disease (MELD) score was 12.2 ± 4.6. The 1-, 3- and 5-year patient survival rate was 96.4% during the mean follow-up period of 57.0 ± 22.4 months. The 1-, 3- and 5-year graft survival rate was 96.4%, 94.2%, and 92.0%, respectively, and no significant differences were observed between ABO-compatible (ABOc) and ABOi grafts (p=0.145). The biliary complication rate showed no significant difference (p=0.195) between ABOc and ABOi grafts. Regeneration rates of ABOi grafts were not significantly different from those of ABOc grafts. DG ALDLT with ABOi and ABOc graft combination seems to be a feasible option for expanding the donor pool without additional donor risks.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-31T03:15:34.382811-05:
      DOI: 10.1111/ajt.14448
  • Kidney allograft offers: Predictors of turndown and the impact of late
           organ acceptance on allograft survival
    • Authors: J.B Cohen; J Shults, D.S Goldberg, P. L Abt, D. L Sawinski, P.P Reese
      Abstract: There is growing interest in understanding patterns of organ acceptance and reducing discard. Little is known about how donor factors, timing of procurement, and geographic location affect organ offer decisions. We performed a retrospective cohort study of 47,563 deceased donor kidney match-runs from 2007-2013. Several characteristics unrelated to allograft quality were independently associated with later acceptance in the match-run: Public Health Service increased-risk donor status (adjusted odds ratio [aOR] 2.49, 95% confidence interval [CI] 2.29-2.69), holiday or weekend procurement (aOR 1.11, 95% CI 1.07-1.16), shorter donor stature (aOR 1.53 for 180 cm, 95% CI 1.28-1.94), and procurement in an area with higher intensity of market competition (aOR 1.71, 95% CI 1.62-1.78) and with the longest waiting times (aOR 1.41, 95% CI 1.34-1.49). Later acceptance in the match-run was associated with delayed graft function but not all-cause allograft failure (adjusted hazard ratio 1.01, 95% CI 0.96-1.07). Study limitations include a lack of match-run data for discarded organs and the possibility of sequence inaccuracies for some non-local matches. Interventions are needed to reduce turndowns of viable organs, especially when decisions are driven by infectious risk, weekend or holiday procurement, geography, or other donor characteristics unrelated to allograft quality.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-31T03:15:32.726169-05:
      DOI: 10.1111/ajt.14449
  • Global Kidney Exchange: Financially Incompatible Pairs Are Not
           Transplantable Compatible Pairs
    • Authors: M. A. Rees; S. Paloyo, A. E. Roth, K. D. Krawiec, O. Ekwenna, C. L. Marsh, A. J. Wenig, T. B. Dunn
      Abstract: Honest debate makes ideas better; we appreciate our colleagues’ engagement. We agree with Wiseman and Gill that Global Kidney Exchange (GKE) must be conducted in an ethical manner that is sensitive to the possibilities of commodification and exploitation and, that it is important to be both careful with and transparent about how patient-donor pairs are selected from developing countries.1,2 We further agree that GKE should continue to be run in a way that enhances rather than competes with local medical services.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-31T03:15:26.664613-05:
      DOI: 10.1111/ajt.14451
  • Ten-Year Outcomes in a Randomized Phase II Study of Kidney Transplant
           Recipients Administered Belatacept 4-Weekly or 8-Weekly
    • Authors: F. Vincenti; G. Blancho, A. Durrbach, G. Grannas, J. Grinyó, H.–U. Meier-Kriesche, M. Polinsky, L. Yang, C. P. Larsen
      Abstract: In the phase II IM103-100 study, kidney transplant recipients were first randomized to belatacept more-intensive–based (n=74), belatacept less-intensive–based (n=71), or cyclosporine-based (n=73) immunosuppression. At 3−6 months posttransplant, belatacept-treated patients were re-randomized to receive belatacept every 4 weeks (4-weekly, n=62) or every 8 weeks (8-weekly, n=60). Patients initially randomized to cyclosporine continued to receive cyclosporine-based immunosuppression. Cumulative rates of biopsy-proven acute rejection (BPAR) from first randomization to year 10 were 22.8%, 37.0%, and 25.8% for belatacept more-intensive, belatacept less-intensive, and cyclosporine, respectively (belatacept more-intensive versus cyclosporine: HR=0.95; 95% CI 0.47−1.92; p=0.89; belatacept less-intensive versus cyclosporine: HR=1.61; 95% CI 0.85−3.05; p=0.15). Cumulative BPAR rates from second randomization to year 10 for belatacept 4-weekly, belatacept 8-weekly, and cyclosporine were 11.1%, 21.9%, and 13.9%, respectively (belatacept 4-weekly versus cyclosporine: HR=1.06, 95% CI 0.35−3.17, p=0.92; belatacept 8-weekly versus cyclosporine: HR=2.00, 95% CI 0.75−5.35, p=0.17). Renal function trends were estimated using a repeated-measures model. Estimated mean GFR values at year 10 for belatacept 4-weekly, belatacept 8-weekly, and CsA were 67.0, 68.7, and 42.7 mL/min per 1.73 m2, respectively (p
      PubDate: 2017-07-31T03:15:25.682527-05:
      DOI: 10.1111/ajt.14452
  • The Outstanding Questions in Transplantation: It's About Time
    • Authors: Jamil Azzi; Giorgio Raimondi, Valeria Mas, Leonardo V. Riella, Nissreen Elfadawy, Kassem Safa, David Wojciechowski, Mazhar Kanak, Rajat Nog, Jonathan Maltzman, Mandy L. Ford, Jordan S. Pober, Xung-Rong Luo, David Rothstein, Michelle L. Miller, David Matthews, William Burlingham, Megan Levings, Peter Heeger, Lauren Higdon, John Gill, Ron Gill, Maria-Luisa Alegre
      Abstract: Organ transplantation represents one of the most daring efforts of science and medicine to challenge end-stage organ diseases and ultimately death. This extraordinary gift of life would not have been possible without the early work of pioneers such as Jaboulay and Carrel in perfecting vascular anastomosis, and the scientific breakthroughs of Medawar and colleagues in understanding immune rejection. Outstanding courage and generosity of organ donors and recipients continue to inspire all of us to do more everyday.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-31T03:15:21.131672-05:
      DOI: 10.1111/ajt.14450
  • Living Donor Follow-up: Unfunded Mandates and the Hippocratic Oath Where
           Perfect may be the Enemy of Good'
    • Authors: D. Sudan
      Abstract: Kidney transplantation in patients with endstage renal disease (ESRD) provides far superior patient survival compared to chronic dialysis. The USRDS report from 2016 demonstrated that the average 3-year survival for patients with ESRD on hemo- or peritoneal dialysis was 56% and 67%, respectively compared to 84% and 91% 3-year survival after deceased donor (DD) and living donor (LD) kidney transplantation (KT), respectively.1 Despite superior patient survival, rates of living donation have decreased since 2005. This is somewhat surprising, given the high mortality for patients on dialysisa, the large kidney transplant waiting list b, the number of DDKT each year (which are far less than number of waitlisted candidates)c, and the high waitlist mortalityd.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-26T14:50:24.819537-05:
      DOI: 10.1111/ajt.14442
  • Microbial metabolites and graft versus host disease
    • Authors: Mary Riwes; Pavan Reddy
      Abstract: The health of mammals is a reflection of the diversity and composition of the intestinal microbiota. Alterations in the composition and functions of the intestinal microbiota have been implicated in multiple disease processes. The impact of the microbiota in health and disease is in part a function of the nutrient processing and release of metabolites. Recent studies have uncovered a major role for microbial metabolites in the function of the host immune system by which they influence disease processes such as acute graft versus host disease (GVHD), which is the main complication of allogeneic hematopoietic cell transplantation (allo-HCT). The mechanisms of acute GVHD regulation by the complex microbial community and the metabolites released by them are unclear. In this review we summarize major findings of how microbial metabolites interact with the immune system and discuss how these interactions could impact acute GVHD.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-25T15:50:24.984483-05:
      DOI: 10.1111/ajt.14443
  • PROviding Better ACcess To ORgans: A Comprehensive Overview of
           Organ-Access Initiatives from the ASTS PROACTOR Task Force
    • Authors: M. J. Hobeika; C. M. Miller, T. L. Pruett, K. A. Gifford, J. E. Locke, A. M. Cameron, M. J. Englesbe, C. S. Kuhr, J. F. Magliocca, K. R. McCune, K. L. Mekeel, S. J. Pelletier, A. L. Singer, D. L. Segev
      Abstract: The American Society of Transplant Surgeons (ASTS) PROviding better Access To Organs (PROACTOR) Task Force was created to inform ongoing ASTS organ access efforts. Task force members were charged with comprehensively cataloguing current organ access activities and organizing them according to stakeholder type. This White Paper summarizes the task force findings and makes recommendations for future ASTS organ access initiatives.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-25T15:50:19.924833-05:
      DOI: 10.1111/ajt.14441
  • Benefits and Limitations of Belatacept in 4 Hand Transplanted Patients
    • Authors: J Grahammer; A Weissenbacher, B G Zelger, B Zelger, C Boesmueller, M Ninkovic, A Mühlbacher, I Peschel, G Brandacher, D Öfner, S Schneeberger
      Abstract: Belatacept (CTLA4Ig) is an emerging treatment in kidney transplantation. Lack of nephrotoxicity and possibly an inhibitory effect on the development of donor specific antibodies (DSA) make it an interesting agent in hand transplantation.In order to reduce CNI immunosuppression and preserve kidney function, we have added belatacept to the therapeutic regimen of 4 hand transplanted patients at month 4, at 6, 9, and 13 years after hand/forearm transplantation. Patients received 5mg/kg belatacept every 2 weeks, the dosing interval was extended to 4 weeks after 5 applications.Belatacept was initially well tolerated in all cases. Two patients were weaned to a low-dose tacrolimus monotherapy together with monthly belatacept applications. One patient is on belatacept with lowered tacrolimus and sirolimus through levels. A fourth patient had significant levels of DSAs at time of conversion and progressed to a severe necrotizing rejection early despite an unaltered baseline immunosuppression. Finger skin necrosis and histological signs of severe chronic allograft vasculopathy eventually led to amputation of the graft.Implementation of belatacept can be beneficial in hand transplantation. However, our findings indicated both potential but also caution and reflection of the immunological state at the time of conversion.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-25T15:45:19.316344-05:
      DOI: 10.1111/ajt.14440
  • Lack of adjustment for confounding could lead to misleading conclusions
    • Authors: S. Christakoudi; M. P. Hernandez-Fuentes
      Abstract: In a recent issue Asare et al. (1) assess the utility of a previously identified signature of tolerance, based on the expression of two B-cell receptor genes (IGKV1D-13 and IGKV4-1). The authors set to determine the prevalence of “tolerance” predictions in treated stable kidney transplant recipients (KTRs) and “tolerance” frequency in patients with different immunosuppressant (IS) regimens. They illustrate (Figure 6), very successfully, that changes in the signature are compatible with known alterations of the B-cell compartment elicited by IS drugs.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-20T10:25:18.22765-05:0
      DOI: 10.1111/ajt.14439
  • Innate Allorecognition by Monocytic Cells and its Role in Graft Rejection
    • Authors: Fadi G. Lakkis; Xian C. Li
      Abstract: Innate recognition of microbial products and danger molecules by monocytes and macrophages has been well established; this is mediated primarily by pattern recognition receptors and is central to activation of innate and adaptive immune cells required for productive immunity. Whether monocytes and macrophages are equipped with an allorecognition system that allows them to directly respond to allogeneic grafts is a topic of much debate. Recent studies provide compelling evidence that these cells are capable of recognizing allogeneic entities and mediate graft rejection via direct cytotoxicity and priming of alloreactive T cells. These studies have also uncovered a mechanism of innate allorecognition based on detection of the polymorphic molecule SIRPα on donor cells. Further understanding of innate allorecognition and its consequences would provide essential insights into allograft rejection and lead to better therapies for transplant patients.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-19T05:55:58.837591-05:
      DOI: 10.1111/ajt.14436
  • The Immunoproteasome: An Old Player with a Novel and Emerging Role in
    • Authors: S. K Eskandari; M. A. J Seelen, G Lin, J. R Azzi
      Abstract: Modern treatment strategies for the maintenance of allograft acceptance frequently target ubiquitously-expressed pathways, leading to significant side-effects and poor long-term allograft outcomes. Constitutive proteasome inhibitors, which have recently been introduced for the treatment of antibody-mediated rejection, target the ubiquitously-expressed proteasome. To limit off-target effects and serious mechanism-based toxicity, however, these inhibitors are administered intermittently and suboptimally. Immunoproteasomes, which are an inducible subset of proteasomes enriched in immune cells, replace constitutive proteasomes after cell exposure to proinflammatory cytokines such as interferon-γ. While immunoproteasomes were first described as processors of antigen for presentation by MHC molecules, recent findings point to its broader biological roles. These vary from activating different subsets of the immune system, by controlling transcriptional activators and downstream cytokines, to affecting their differentiation and survival. These emerging roles of the immunoproteasome in activated immune cells have made it a rational candidate for the targeted treatment of immune-mediated diseases. Preclinical studies have established its role in maintaining allograft acceptance without significant short- or long-term toxicity. This review provides a brief background of the immunoproteasome and outlines its role in immunological pathways and its potential in alloimmunity.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-18T10:29:38.17577-05:0
      DOI: 10.1111/ajt.14435
  • Human immunology studies using organ donors: impact of clinical variations
           on immune parameters in tissues and circulation
    • Authors: D. J. Carpenter; T. Granot, N. Matsuoka, T. Senda, B. V. Kumar, J. J. C. Thome, C. L. Gordon, M. Miron, J. Weiner, T. Connors, H. Lerner, A. Friedman, T. Kato, A. D. Griesemer, D. L. Farber
      Abstract: Organ donors are sources of physiologically healthy organs and tissues for life-saving transplantation, and have been recently used for human immunology studies which are typically confined to the sampling of peripheral blood. Donors comprise a diverse population with different causes of death and clinical outcomes during hospitalization, and the effects of such variations on immune parameters in blood and tissues are not known. We present here coordinate analyses of innate and adaptive immune components in blood, lymphoid (bone marrow, spleen, lymph nodes), and mucosal (lungs, intestines) sites from a population of brain-dead organ donors (3-months-93-years; n=291) across eight clinical parameters. Overall, the blood of donors exhibited similar monocyte and lymphocyte content and low serum levels of pro-inflammatory cytokines as healthy controls; however, donor blood had increased neutrophils and serum levels of IL-8, IL-6 and MCP-1 which varied with cause of death. In tissues, the frequency and composition of monocytes, neutrophils, B lymphocytes and T cell subsets in lymphoid or mucosal sites did not vary with clinical state, and was similar in donors independent of the extent of clinical complications. Our results reveal that organ donor maintain tissue homeostasis, and are a valuable resource for fundamental studies in human immunology.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-18T10:29:12.924466-05:
      DOI: 10.1111/ajt.14434
  • Pancreatic Allograft Thrombosis: Suggestion for a CT grading system and
           management algorithm
    • Authors: Abdul Hakeem; John Chen, Satheesh Iype, Menna Clatworthy, Christopher Watson, Edmund M Godfrey, Sara Upponi, Kourosh Saeb-Parsy
      Abstract: Pancreatic allograft thrombosis (PAT) remains the leading cause of non-immunological graft failure. Herein we propose a new CT grading system of PAT to identify risk factors for allograft loss and outline a management algorithm by retrospective review of consecutive pancreatic transplants between 2009-2014. Triple-phase CT scans were graded independently by two radiologists as; Grade 0 – no thrombosis, Grade 1 – peripheral thrombosis, Grade 2 – intermediate non-occlusive thrombosis and Grade 3 – central occlusive thrombosis. Twenty-four of 103 (23.3%) recipients were diagnosed with PAT (including grade 1). Three grafts (2.9%) were lost due to portal vein thrombosis. On multivariate analysis, pancreas after SPK/PAK transplant, acute rejection and CT finding peri-pancreatic oedema and/or inflammatory change were significant risk factors of PAT. Retrospective review of CT images revealed more grade 1 and 2 thromboses than were initially reported. There was no significant difference in graft or patient survival, post-operative stay or morbidity of recipients with grade 1 or 2 thrombosis who were or were not anticoagulated. Our data suggest that therapeutic anticoagulation is not necessary for grade 1 and 2 arterial and grade 1 venous thrombosis. The proposed grading system can assist clinicians in decision making and provide standardised reporting for future studies.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-18T10:28:04.950358-05:
      DOI: 10.1111/ajt.14433
  • Pre-Kidney Transplant Lower Extremity Impairment and Post-Transplant
    • Authors: Anthony J. Nastasi; Mara A. McAdams-DeMarco, Jennifer Schrack, Hao Ying, Israel Olorundare, Fatima Warsame, Alexandra Mountford, Christine E. Haugen, Marlís González Fernández, Silas P. Norman, Dorry L. Segev
      Abstract: Prediction models for post-kidney transplant (KT) mortality have had limited success (C-statistics≤0.70). Adding objective measures of potentially modifiable factors may improve prediction and, consequently, KT survival through intervention. The short physical performance battery (SPPB) is an easily administered objective test of lower extremity function consisting of three parts (balance, walking speed, chair stands), each with scores of 0-4, for a composite score of 0-12, with higher scores indicating better function. SPPB performance and frailty (Fried frailty phenotype) were assessed at admission for KT in a prospective cohort of 719 KT recipients at Johns Hopkins Hospital (8/2009-6/2016) and University of Michigan (2/2013-12/2016). The independent associations between SPPB impairment (SPPB composite score≤10) and composite score with post-KT mortality were tested using adjusted competing risks models treating graft failure as a competing risk. The 5-year post-KT mortality for impaired recipients was 20.6% compared to 4.5% for unimpaired recipients (P
      PubDate: 2017-07-15T12:10:29.42438-05:0
      DOI: 10.1111/ajt.14430
  • Belatacept rescue therapy in kidney transplant recipients with vascular
           lesions: a case control study
    • Authors: D. Bertrand; L. Cheddani, I. Etienne, A. François, M. Hanoy, C. Laurent, L. Lebourg, F. Le Roy, L. Lelandais, M C Loron, M. Godin, D. Guerrot
      Abstract: Immunosuppression in kidney transplant recipients with decreased graft function and severe histological vascular changes can be particularly challenging. Belatacept could be a valuable option, as a rescue therapy in this context.We report a retrospective case control study comparing a CNI to belatacept switch in 17 patients with vascular damage and low eGFR to a control group of 18 matched patients with CNI continuation. Belatacept switch was performed on average 51.5 months after kidney transplantation (6.2-198 months). There was no difference between the two groups regarding eGFR at inclusion, and 3 months before inclusion. In the “CNI to belatacept switch group”, mean eGFR increased significantly from 23.5±6.7 mL/min/1.73m2 on day 0, to 30.4±9.1 ml/min/1.73m2 on month 6 (p
      PubDate: 2017-07-14T04:25:37.816382-05:
      DOI: 10.1111/ajt.14427
  • Impact of Protease Inhibitor based Anti-Retroviral Therapy on Outcomes for
           HIV+ Kidney Transplant Recipients
    • Authors: Deirdre Sawinski; Brittany A. Shelton, Shikha Mehta, Rhiannon D. Reed, Paul A. MacLennan, Sally Gustafson, Dorry L. Segev, Jayme E. Locke
      Abstract: Excellent outcomes have been demonstrated among select HIV-positive kidney transplant (KT) recipients with well-controlled infection, but to date no national study has explored outcomes among HIV+ KT recipients by antiretroviral therapy (ART) regimen. IMS pharmacy fills (1/1/01 - 10/1/12) were linked with SRTR data. 332 recipients with pre- and post-transplant fills were characterized by ART at time of transplant as protease inhibitor (PI) or non-PI based ART (88 PI vs. 244 non-PI). Cox proportional hazards models were adjusted for recipient and donor characteristics. Comparing recipients by ART regimen, there were no significant differences in age, race, or HCV status. Recipients on PI-based regimens were significantly more likely to have an estimated post-transplant score (EPTS)> 20% (70.9% vs. 56.3%, p=0.02) than those on non-PI regimens. On adjusted analyses, PI-based regimens were associated with 1.8-fold increased risk of allograft loss (aHR: 1.84, 95%CI: 1.22-2.77, p=0.003), with the greatest risk observed in the first post-transplant year (aHR: 4.48, 95%CI: 1.75-11.48, p=0.002), and 1.9-fold increased risk of death as compared to non-PI regimens (aHR: 1.91, 95%CI: 1.02-3.59, p=0.05). These results suggest whenever possible recipients should be converted to a non-PI regimen prior to KT.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-11T04:45:22.969216-05:
      DOI: 10.1111/ajt.14419
  • Mechanical Ventilation and Extracorporeal Membrane Oxygenation as a
           Bridging Strategy to Lung Transplantation: Significant Gains in Survival
    • Authors: Awori J. Hayanga; Angela L. Du, Kyla Joubert, Tuft Marie, Rachel Baird, Joseph Pilewski, Mathew Morrell, Jonathan D'Cunha, Norihisa Shigemura
      Abstract: Mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO) are increasingly used to bridge patients to lung transplantation. We investigated the impact of using MV, with or without ECMO, prior to lung transplantation on survival after transplantation by performing a retrospective analysis of 826 patients who underwent transplantation at our high-volume center. Recipient characteristics and posttransplant outcomes were analyzed. Most lung transplant recipients (729 patients) did not require bridging; 194 of these patients were propensity matched with patients who were bridged using MV alone (48 patients) or MV and ECMO (49 patients). There was no difference in overall survival between the MV and MV+ECMO groups (p=0.07). The MV+ECMO group had significantly higher survival conditioned on surviving to one year (median 1811 days (MV) vs. not reached (MV+ECMO), p=0.01). Recipients in the MV+ECMO group, however, were more likely to require ECMO after lung transplantation (16.7% MV vs. 57.1% MV+ECMO, p
      PubDate: 2017-07-11T03:05:30.005696-05:
      DOI: 10.1111/ajt.14422
  • Skin Cancers in Organ Transplant Recipients
    • Authors: Amit Mittal; Oscar R. Colegio
      Abstract: Long-term utilization of immunosuppression in organ transplant recipients (OTRs) leads to decreased immune-mediated tumor surveillance and development of malignant tumors. A delicate balance needs to be maintained in the intensity of immunosuppression to keep the risk of malignancy low without jeopardizing life-saving graft function. OTRs are prone to developing skin cancers which exhibit unique epidemiologic, pathophysiologic and prognostic characteristics. In this review, we discuss the most commonly reported skin cancers in OTRs: squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Kaposi's sarcoma, Merkel cell carcinoma and malignant melanoma (MM). Tumors in this high-risk population are aggressive and may respond poorly to standard therapies. However, new targeted therapies are promising. Checkpoint inhibitor antibodies have been used for treatment of cutaneous SCC, Merkel cell carcinoma, and MM; epidermal growth factor receptor inhibitors for cutaneous SCC; hedgehog pathway inhibitors for BCC; and BRAF and MEK inhibitors are being used increasingly in the management of MM. Guidelines for dermatologic screening is variable and primarily based on expert opinion. Prospective evidence-based trials by multidisciplinary groups are needed to better define surveillance schedules for pre-transplant and post-transplant cutaneous malignancies.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-29T01:25:31.690654-05:
      DOI: 10.1111/ajt.14382
  • Comprehensive Review on Colorectal Cancer and Transplant
    • Authors: S. Prenner; J. Levitsky
      Abstract: Colon cancer (CRC) is a common malignancy worldwide. Some studies suggest that organ recipients are at a higher risk for CRC than the general population. The underlying transplant indications and their inherent risk factors for CRC may drive the variation in incidence rates that are seen in patients receiving different allografts. Recipients with cystic fibrosis are now recognized as a population at high risk for CRC at a young age. Transplant recipients have high mortality following a CRC diagnosis, even if it is detected at an early stage. Certain types of immunosuppression have been shown to accelerate cancer transformation and may contribute to the more aggressive phenotype seen in organ recipients. Given the high incidence and progressive nature of post-transplant CRC, shorter screening intervals with a modality that can detect early stage polyps may be essential to prevent mortality. Future research is needed to better elucidate the role of immunosuppression in carcinogenesis. This comprehensive review examines CRC risk, screening, and management specific to organ transplant candidates and recipients.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-04T09:41:39.740429-05:
      DOI: 10.1111/ajt.14340
  • Global Kidney Exchange: Overcoming the Barrier of Poverty
    • Authors: Lara C. Pullen
      Pages: 2499 - 2500
      Abstract: This month's installment of “The AJT Report” debates the benefits, ethics and sustainability of Global Kidney Exchange. We also look at efforts to shore kidney paired donation implementation in the United States.
      PubDate: 2017-09-28T09:36:38.02383-05:0
      DOI: 10.1111/ajt.14469
  • Predicting TCR specificity'
    • Authors: Maria-Luisa Alegre
      Pages: 2501 - 2501
      Abstract: Sequence similarity between short stretches of DNA within rearranged TCR CDR3 gene segments predicts T cells that recognize the same antigen.
      PubDate: 2017-09-28T09:36:36.491473-05:
      DOI: 10.1111/ajt.14470
  • Unlocking the Potential of Organ Donation
    • Authors: J. M. Smits
      Pages: 2503 - 2504
      Abstract: This editorial further discusses standardization of the donor selection process in the United States and identification of the factors behind donor nonuse as reported by Kobashigawa et al on page 2559.
      PubDate: 2017-07-27T08:15:22.343664-05:
      DOI: 10.1111/ajt.14412
  • Life After Death: Breathing Life Into Lung Transplantation From Donation
           After Circulatory Death Donors
    • Authors: S. J. Bozso; J. Nagendran
      Pages: 2507 - 2508
      Abstract: A proposed standardized algorithm from van Suylen et al (page 2679) may safely increase rates of transplantation of donation after circulatory death donors in lung transplantation by objectively defining criteria for transplant suitability of acceptable and nonacceptable donor lungs.
      PubDate: 2017-07-25T09:25:21.732068-05:
      DOI: 10.1111/ajt.14413
  • The Resurgence of Xenotransplantation
    • Authors: P. J. Cowan; A. J. Tector
      Pages: 2531 - 2536
      Abstract: There has been an upsurge of interest in xenotransplantation in recent years. This resurgence can attributed to a combination of factors. First, there has been a dramatic improvement in efficacy in several preclinical models, with maximum xenograft survival times increasing to 950 days for islets, 945 days for hearts, and 310 days for kidneys. Second, the rapid development of genome editing technology (particularly the advent of clustered regularly interspaced short palindromic repeats/Cas9) has revolutionized the capacity to generate new donor pigs with multiple protective genetic modifications; what once took many years to achieve can now be performed in months, with much greater precision and scope. Third, the specter of porcine endogenous retrovirus (PERV) has receded significantly. There has been no evidence of PERV transmission in clinical trials and preclinical models, and improved screening methods and new options for the treatment or even elimination of PERV are now available. Balancing these positive developments are several remaining challenges, notably the heavy and often clinically inapplicable immunosuppression required to prevent xenograft rejection. Nonetheless, the potential for xenotransplantation as a solution to the shortage of human organs and tissues for transplantation continues to grow.
      PubDate: 2017-05-08T09:15:43.523835-05:
      DOI: 10.1111/ajt.14311
  • Prevention of the Osmotic Demyelination Syndrome After Liver
           Transplantation: A Multidisciplinary Perspective
    • Authors: J. F. Crismale; K. A. Meliambro, S. DeMaria, D. B. Bronster, S. Florman, T. D. Schiano
      Pages: 2537 - 2545
      Abstract: The osmotic demyelination syndrome (ODS) is a serious neurologic condition that occurs in the setting of rapid correction of hyponatremia. It presents with protean manifestations, from encephalopathy to the “locked-in” syndrome. ODS can complicate liver transplantation (LT), and its incidence may increase with the inclusion of serum sodium as a factor in the Mayo End-Stage Liver Disease score. A comprehensive understanding of risk factors for the development of ODS in the setting of LT, along with recommendations to mitigate the risk of ODS, are necessary. The literature to date on ODS in the setting of LT was reviewed. Major risk factors for the development of ODS include severe pretransplant hyponatremia (serum sodium [SNa] < 125 mEq/L), the magnitude of change in SNa pre- versus posttransplant, higher positive intraoperative fluid balance, and the presence of postoperative hemorrhagic complications. Strategies to reduce the risk of ODS include correcting hyponatremia pretransplant via fluid restriction and/or ensuring an appropriate rate of increase from the preoperative SNa via close attention to fluid and electrolyte management both during and after surgery. Multidisciplinary management involving transplant hepatology, nephrology, neurology, surgery, and anesthesiology/critical care is key to performing LT safely in patients with hyponatremia.
      PubDate: 2017-05-26T08:56:18.597105-05:
      DOI: 10.1111/ajt.14317
  • Report From the American Society of Transplantation Conference on Donor
           Heart Selection in Adult Cardiac Transplantation in the United States
    • Authors: J. Kobashigawa; K. Khush, M. Colvin, M. Acker, A. Van Bakel, H. Eisen, Y. Naka, J. Patel, D. A. Baran, T. Daun, M. Luu, M. Olymbios, J. Rogers, V. Jeevanandam, F. Esmailian, F. D. Pagani, B. Lima, J. Stehlik
      Pages: 2559 - 2566
      Abstract: Cardiac transplantation remains the only definitive treatment for end-stage heart failure. Transplantation rates are limited by a shortage of donor hearts. This shortage is magnified because many hearts are discarded because of strict selection criteria and concern for regulatory reprimand for less-than-optimal posttransplant outcomes. There is no standardized approach to donor selection despite proposals to liberalize acceptance criteria. A donor heart selection conference was organized to facilitate discussion and generate ideas for future research. The event was attended by 66 participants from 41 centers with considerable experience in cardiac donor selection. There were state-of-the-art presentations on donor selection, with subsequent breakout sessions on standardizing the process and increasing utilization of donor hearts. Participants debated misconceptions and established agreement on donor and recipient risk factors for donor selection and identified the components necessary for a future donor risk score. Ideas for future initiatives include modification of regulatory practices to consider extended criteria donors when evaluating outcomes and prospective studies aimed at identifying the factors leading to nonacceptance of available donor hearts. With agreement on the most important donor and recipient risk factors, it is anticipated that a consistent approach to donor selection will improve rates of heart transplantation.
      PubDate: 2017-06-13T08:50:56.509442-05:
      DOI: 10.1111/ajt.14354
  • Considering Tangible Benefit for Interdependent Donors: Extending a
           Risk–Benefit Framework in Donor Selection
    • Authors: S. E. Van Pilsum Rasmussen; M. L. Henderson, J. Kahn, D. Segev
      Pages: 2567 - 2571
      Abstract: From its infancy, live donor transplantation has operated within a framework of acceptable risk to donors. Such a framework presumes that risks of living donation are experienced by the donor while all benefits are realized by the recipient, creating an inequitable distribution that demands minimization of donor risk. We suggest that this risk-tolerance framework ignores tangible benefits to the donor. A previously proposed framework more fully considers potential benefits to the donor and argues that risks and benefits must be balanced. We expand on this approach, and posit that donors sharing a household with and/or caring for a potential transplant patient may realize tangible benefits that are absent in a more distantly related donation (e.g. cousin, nondirected). We term these donors, whose well-being is closely tied to their recipient, “interdependent donors.” A flexible risk–benefit model that combines risk assessment with benefits to interdependent donors will contribute to donor evaluation and selection that more accurately reflects what is at stake for donors. In so doing, a risk–benefit framework may allow some donors to accept greater risk in donation decisions.
      PubDate: 2017-05-17T10:15:25.289283-05:
      DOI: 10.1111/ajt.14319
  • Prolonged Cold Ischemia Time Results in Local and Remote Organ Dysfunction
           in a Murine Model of Vascularized Composite Transplantation
    • Authors: N. Datta; S. G. Devaney, R. W. Busuttil, K. Azari, J. W. Kupiec-Weglinski
      Pages: 2572 - 2579
      Abstract: Vascularized composite allotransplantation (VCA) is a viable reconstructive option for complex tissue defects. Although grafts with a large muscular component may be uniquely susceptible to ischemia–reperfusion (I/R) syndrome, the safe cold ischemia time in VCA has not been established. We investigated the effects of cold ischemia on innate immune response and recipient survival in a murine orthotopic hindlimb transplantation model. Surprisingly, mice receiving grafts exposed to 6 h or longer of cold storage demonstrated reduced survival and massive elevations in serum creatinine, blood urea nitrogen, and creatine kinase, compared with 1 h of cold storage recipients. This was accompanied by progressive increase in macrophage and neutrophil cell infiltration in muscle biopsy specimens, altered platelet endothelial cell adhesion molecule-1 expression, and ultimate renal injury. Multiplex immunoassay analysis identified 21 cytokines in serum and 18 cytokines in muscle biopsy specimens that are likely essential in the complex response to I/R-triggered injury in VCA. In conclusion, this study, in a mouse model of orthotopic hindlimb transplantation, is the first to document that prolonged cold ischemia triggers progressive I/R injury with vascular endothelial damage and may lead to irrecoverable local and remote organ damage. These experimental findings are important in guiding future therapies for human VCA recipients.
      PubDate: 2017-05-09T09:45:31.138255-05:
      DOI: 10.1111/ajt.14290
  • Normothermic Ex Vivo Kidney Perfusion Following Static Cold
           Storage—Brief, Intermediate, or Prolonged Perfusion for Optimal Renal
           Graft Reconditioning'
    • Authors: J. M. Kaths; J. Echeverri, I. Linares, J. Y. Cen, S. Ganesh, M. Hamar, P. Urbanellis, P. Yip, R. John, D. Bagli, I. Mucsi, A. Ghanekar, D. Grant, L. A. Robinson, M. Selzner
      Pages: 2580 - 2590
      Abstract: Normothermic ex vivo kidney perfusion (NEVKP) demonstrated superior results compared to hypothermic storage in donation after circulatory death (DCD) kidney transplantation. It is unknown whether an optimal perfusion time exists following hypothermic storage to allow for the recovery of renal grafts from cold ischemic injury. In a porcine model of DCD kidney autotransplantation, the impact of initial static cold storage (SCS) (8 h) followed by various periods of NEVKP recovery was investigated: group A, 8 hSCS only (control); group B, 8 hSCS + 1 hNEVKP (brief NEVKP); group C, 8 hSCS + 8 hNEVKP (intermediate NEVKP); and group D, 8 hSCS + 16 hNEVKP (prolonged NEVKP). All grafts were preserved and transplanted successfully. One animal in group D was sacrificed and excluded by postoperative day 3 due to hind limb paralysis, but demonstrated good renal function. Postoperative graft assessment during 8 days’ follow-up demonstrated lowest levels of peak serum creatinine for intermediate (C) and prolonged (D) NEVKP (p = 0.027). Histological assessment on day 8 demonstrated a significant difference in tubular injury (p = 0.001), with highest values for group B. These results suggest that longer periods of NEVKP following SCS are feasible and safe for postponing surgical transplant procedure and superior to brief NEVKP, reducing the damage caused during cold ischemic storage of renal grafts.
      PubDate: 2017-05-08T09:05:48.691475-05:
      DOI: 10.1111/ajt.14294
  • BK Polyomavirus-Specific 9mer CD8 T Cell Responses Correlate With
           Clearance of BK Viremia in Kidney Transplant Recipients: First Report From
           the Swiss Transplant Cohort Study
    • Authors: C. Leboeuf; S. Wilk, R. Achermann, I. Binet, D. Golshayan, K. Hadaya, C. Hirzel, M. Hoffmann, U. Huynh-Do, M. T. Koller, O. Manuel, N. J. Mueller, T. F. Mueller, S. Schaub, C. Delden, F. H. Weissbach, H. H. Hirsch,
      Pages: 2591 - 2600
      Abstract: BK polyomavirus (BKPyV) causes premature kidney transplant (KT) failure in 1–15% of patients. Because antivirals are lacking, most programs screen for BKPyV-viremia and, if positive, reduce immunosuppression. To evaluate the relationship of viremia and BKPyV-specific immunity, we examined prospectively cryopreserved plasma and peripheral blood mononuclear cells at the time of transplantation (T0) and at 6 mo (T6) and 12 mo (T12) after transplant from 28 viremic KT patients and 68 nonviremic controls matched for the transplantation period. BKPyV IgG seroprevalence was comparable between cases (89.3%) and controls (91.2%; p = 0.8635), but cases had lower antibody levels (p = 0.022) at T0. Antibody levels increased at T6 and T12 but were not correlated with viremia clearance. BKPyV-specific T cell responses to pools of overlapping 15mers (15mer peptide pool [15mP]) or immunodominant CD8 9mers (9mer peptide pool [9mP]) from the early viral gene region were not different between cases and controls at T0; however, clearance of viremia was associated with stronger 9mP responses at T6 (p = 0.042) and T12 (p = 0.048), whereas 15mP responses were not informative (T6 p = 0.359; T12 p = 0.856). BKPyV-specific T cells could be expanded in vitro from all patients after transplant, permitting identification of 78 immunodominant 9mer epitopes including 50 new ones across different HLA class I. Thus, 9mP-responses may be a novel marker of reconstituting CD8 T cell function that warrants further study as a complement of plasma BKPyV loads for guiding immunosuppression reduction.
      PubDate: 2017-04-25T09:36:37.158-05:00
      DOI: 10.1111/ajt.14282
  • Effect of Empagliflozin on Tacrolimus-Induced Pancreas Islet Dysfunction
           and Renal Injury
    • Authors: J. Jin; L. Jin, K. Luo, S. W. Lim, B. H. Chung, C. W. Yang
      Pages: 2601 - 2616
      Abstract: An inhibitor of sodium glucose co-transporter type 2 (SGLT-2) is recommended in type 2 diabetes mellitus (DM) but its use is still undetermined in tacrolimus (TAC)-induced DM. We evaluated the effect of empagliflozin (Em) on TAC-induced pancreatic islet dysfunction and renal injury in an experimental model of TAC-induced DM and in vitro. TAC induced a twofold increase in SGLT-2 expression, while Em decreased SGLT-2 expression and further increased urinary glucose excretion compared to the TAC group. Em reduced hyperglycemia and increased plasma insulin level, pancreatic islet size, and glucose-stimulated insulin secretion compared to the TAC group. In kidney, Em alleviated TAC-induced renal dysfunction and decreased albumin excretion and histological injury compared with the TAC group. Increased oxidative stress and apoptotic cell death by TAC was remarkably decreased with Em in serum and pancreatic and renal tissues. In in vitro study, TAC decreased cell viability and increased reactive oxygen species (ROS) production in both insulin-secreting beta-cell derived (INS-1) and human kidney-2 (HK-2) cell lines. Addition of Em increased cell viability and decreased ROS production in HK-2 but not in INS-1 cell lines. This suggests that Em is effective in controlling TAC-induced hyperglycemia and has direct protective effect on TAC-induced renal injury.
      PubDate: 2017-05-20T10:40:37.943565-05:
      DOI: 10.1111/ajt.14316
  • A Memory B Cell Crossmatch Assay for Quantification of Donor-Specific
           Memory B Cells in the Peripheral Blood of HLA-Immunized Individuals
    • Authors: G. E. Karahan; Y. J. H. Vaal, J. Krop, C. Wehmeier, D. L. Roelen, F. H. J. Claas, S. Heidt
      Pages: 2617 - 2626
      Abstract: Humoral responses against mismatched donor HLA are routinely measured as serum HLA antibodies, which are mainly produced by bone marrow–residing plasma cells. Individuals with a history of alloimmunization but lacking serum antibodies may harbor circulating dormant memory B cells, which may rapidly become plasma cells on antigen reencounter. Currently available methods to detect HLA-specific memory B cells are scarce and insufficient in quantifying the complete donor-specific memory B cell response due to their dependence on synthetic HLA molecules. We present a highly sensitive and specific tool for quantifying donor-specific memory B cells in peripheral blood of individuals using cell lysates covering the complete HLA class I and class II repertoire of an individual. Using this enzyme-linked immunospot (ELISpot) assay, we found a median frequency of 31 HLA class I and 89 HLA class II–specific memory B cells per million IgG-producing cells directed at paternal HLA in peripheral blood samples from women (n = 22) with a history of pregnancy, using cell lysates from spouses. The donor-specific memory B cell ELISpot can be used in HLA diagnostic laboratories as a cross-match assay to quantify donor-specific memory B cells in patients with a history of sensitizing events.
      PubDate: 2017-05-03T08:16:17.216854-05:
      DOI: 10.1111/ajt.14293
  • B Cell Receptor Genes Associated With Tolerance Identify a Cohort of
           Immunosuppressed Patients With Improved Renal Allograft Graft Function
    • Authors: A. Asare; S. Kanaparthi, N. Lim, D. Phippard, F. Vincenti, J. Friedewald, M. Pavlakis, E. Poggio, P. Heeger, R. Mannon, B. E. Burrell, Y. Morrison, N. Bridges, I. Sanz, A. Chandraker, K. A. Newell, L. A. Turka
      Pages: 2627 - 2639
      Abstract: We previously reported that two B cell receptor genes, IGKV1D-13 and IGKV4-1, were associated with tolerance following kidney transplantation. To assess the potential utility of this “signature,” we conducted a prospective, multicenter study to determine the frequency of patients predicted tolerant within a cohort of patients deemed to be candidates for immunosuppressive minimization. At any single time point, 25–30% of patients were predicted to be tolerant, while 13.7% consistently displayed the tolerance “signature” over the 2-year study. We also examined the relationship of the presence of the tolerance “signature” on drug use and graft function. Contrary to expectations, the frequency of predicted tolerance was increased in patients receiving tacrolimus and reduced in those receiving corticosteroids, mycophenolate mofetil, or Thymoglobulin as induction. Surprisingly, patients consistently predicted to be tolerant displayed a statistically and clinically significant improvement in estimated glomerular filtration rate that increased over time following transplantation. These findings indicate that the frequency of patients consistently predicted to be tolerant is sufficiently high to be clinically relevant and confirm recent findings by others that immunosuppressive agents impact putative biomarkers of tolerance. The association of a B cell–based “signature” with graft function suggests that B cells may contribute to the function/survival of transplanted kidneys.
      PubDate: 2017-05-02T11:05:15.49861-05:0
      DOI: 10.1111/ajt.14283
  • Urinary Markers of Fibrosis and Risk of Cardiovascular Events and Death in
           Kidney Transplant Recipients: The FAVORIT Trial
    • Authors: M. Park; R. Katz, M. G. Shlipak, D. Weiner, R. Tracy, V. Jotwani, J. Hughes-Austin, F. Gabbai, C. Y. Hsu, M. Pfeffer, N. Bansal, A. Bostom, O. Gutierrez, M. Sarnak, A. Levey, J. H. Ix
      Pages: 2640 - 2649
      Abstract: Cardiovascular risk remains high in kidney transplant recipients (KTRs) despite improved kidney function after transplant. Urinary markers of kidney fibrosis and injury may help to reveal mechanisms of this risk. In a case–cohort study among stable KTRs who participated in the FAVORIT trial, we measured four urinary proteins known to correlate with kidney tubulointerstitial fibrosis on biopsy (urine alpha 1 microglobulin [α1m], monocyte chemoattractant protein-1 [MCP-1], procollagen type I [PINP] and type III [PIIINP] N-terminal amino peptide) and evaluated associations with cardiovascular disease (CVD) events (n = 300) and death (n = 371). In adjusted models, higher urine α1m (hazard ratio [HR] per doubling of biomarker 1.40 [95% confidence interval [CI] 1.21, 1.62]), MCP-1 (HR 1.18 [1.03, 1.36]), and PINP (HR 1.13 [95% CI 1.03, 1.23]) were associated with CVD events. These three markers were also associated with death (HR per doubling α1m 1.51 [95% CI 1.32, 1.72]; MCP-1 1.31 [95% CI 1.13, 1.51]; PINP 1.11 [95% CI 1.03, 1.20]). Higher concentrations of urine α1m, MCP-1, and PINP may identify KTRs at higher risk for CVD events and death. These markers may identify a systemic process of fibrosis involving both the kidney and cardiovascular system, and give new insights into mechanisms linking the kidney with CVD.
      PubDate: 2017-04-26T09:07:44.852796-05:
      DOI: 10.1111/ajt.14284
  • Incidence and Predictors of Cancer Following Kidney Transplantation in
    • Authors: A. Francis; D. W. Johnson, J. C. Craig, G. Wong
      Pages: 2650 - 2658
      Abstract: Cancer risk is increased substantially in adult kidney transplant recipients, but the long-term risk of cancer in childhood recipients is unclear. Using the Australian and New Zealand Dialysis and Transplant Registry, the authors compared overall and site-specific incidences of cancer after transplantation in childhood recipients with population-based data by using standardized incidence ratios (SIRs). Among 1734 childhood recipients (median age 14 years, 57% male, 85% white), 289 (16.7%) developed cancer (196 nonmelanoma skin cancers, 143 nonskin cancers) over a median follow-up of 13.4 years. The 25-year cumulative incidences of any cancer were 27% (95% confidence intervals 24–30%), 20% (17–23%) for nonmelanoma skin cancer, and 14% (12–17%) for nonskin cancer (including melanoma). The SIR for nonskin cancer was 8.23 (95% CI 6.92–9.73), with the highest risk for posttransplant lymphoproliferative disease (SIR 45.80, 95% CI 32.71–62.44) and cervical cancer (29.4, 95% CI 17.5–46.5). Increasing age at transplantation (adjusted hazard ratio [aHR] per year 1.10, 95% CI 1.06–1.14), white race (aHR 3.36, 95% CI 1.61–6.79), and having a functioning transplant (aHR 2.27, 95% CI 1.47–3.71) were risk factors for cancer. Cancer risk, particularly for virus-related cancers, is increased substantially after kidney transplantation during childhood.
      PubDate: 2017-05-08T09:00:27.938734-05:
      DOI: 10.1111/ajt.14289
  • Pretransplant Numbers of CD16+ Monocytes as a Novel Biomarker to Predict
           Acute Rejection After Kidney Transplantation: A Pilot Study
    • Authors: T. P. P. Bosch; L. B. Hilbrands, R. Kraaijeveld, N. H. R. Litjens, F. Rezaee, D. Nieboer, E. W. Steyerberg, J. A. Gestel, D. L. Roelen, M. C. Clahsen-van Groningen, C. C. Baan, A. T. Rowshani
      Pages: 2659 - 2667
      Abstract: Acute rejection is one of the major immunological determinants of kidney graft function and survival. Early biomarkers to predict rejection are lacking. Emerging evidence reveals a crucial role for the monocyte/macrophage lineage cells in the pathogenesis of rejection. We hypothesized that higher pretransplant numbers of proinflammatory CD16+ monocytes can predict rejection. The study cohort consisted of 104 kidney transplant recipients (58 with no rejection and 46 with biopsy-proven rejection) and 33 healthy persons. Posttransplant median follow-up time was 14.7 mo (interquartile range 0.3–34 mo). Pretransplantation blood samples were analyzed by flow cytometry for monocyte immunophenotypes. Groups were compared by Cox regression models for the occurrence of acute rejection. We documented a significantly increased absolute number of pretransplant CD16+ monocytes in patients who developed biopsy-proven rejection after transplantation compared with those with no rejection (hazard ratio [HR] 1.60, 95% CI 1.28–2.00, p < 0.001) and healthy persons (HR 1.47, 95% CI 1.18–1.82, p < 0.001). In parallel, significantly fewer absolute numbers of CD16− monocytes were observed at pretransplant time points in rejectors versus nonrejectors (HR 0.74, 95% CI 0.58–0.94, p < 0,014). A higher pretransplant number of CD16+ monocytes is significantly associated with a higher risk of acute rejection after kidney transplantation.
      PubDate: 2017-04-22T10:45:45.738728-05:
      DOI: 10.1111/ajt.14280
  • The Medication Level Variability Index (MLVI) Predicts Poor Liver
           Transplant Outcomes: A Prospective Multi-Site Study
    • Authors: E. Shemesh; J. C. Bucuvalas, R. Anand, G. V. Mazariegos, E. M. Alonso, R. S. Venick, M. Reyes-Mugica, R. A. Annunziato, B. L. Shneider
      Pages: 2668 - 2678
      Abstract: Nonadherence to immunosuppressant medications is a leading cause of poor long-term outcomes in transplant recipients. The Medication Level Variability Index (MLVI) provides a vehicle for transplant outcome risk-stratification through continuous assessment of adherence. The MALT (Medication Adherence in children who had a Liver Transplant) prospective multi-site study evaluated whether MLVI predicts late acute rejection (LAR). Four hundred pediatric (1–17-year-old) liver transplant recipients were enrolled and followed for 2 years. The a-priori hypothesis was that a higher MLVI predicts LAR. Predefined secondary analyses evaluated other outcomes such as liver enzyme levels, and sensitivity analyses compared adolescents to pre-adolescents. In the primary analysis sample of 379 participants, a higher prerejection MLVI predicted LAR (mean prerejection MLVI with LAR: 2.4 [3.6 standard deviation] versus without LAR, 1.6 [1.1]; p = 0.026). Fifty-three percent of the adolescents with MLVI>2 in year 1 had LAR by the end of year 2, as compared with 6% of those with year 1 MLVI≤2. A higher MLVI was significantly associated with all secondary outcomes. MLVI, a marker of medication adherence that uses clinically derived information, predicts LAR in pediatric liver transplant recipients.
      PubDate: 2017-04-22T10:40:57.427521-05:
      DOI: 10.1111/ajt.14276
  • A Multicenter Study on Long-Term Outcomes After Lung Transplantation
    • Authors: V. Suylen; B. Luijk, R. A. S. Hoek, E. A. Graaf, E. A. Verschuuren, C. Van De Wauwer, J. A. Bekkers, R. C. A. Meijer, W. Bij, M. E. Erasmus
      Pages: 2679 - 2686
      Abstract: The implementation of donation after circulatory death category 3 (DCD3) was one of the attempts to reduce the gap between supply and demand of donor lungs. In the Netherlands, the total number of potential lung donors was greatly increased by the availability of DCD3 lungs in addition to the initial standard use of donation after brain death (DBD) lungs. From the three lung transplant centers in the Netherlands, 130 DCD3 recipients were one-to-one nearest neighbor propensity score matched with 130 DBD recipients. The primary end points were primary graft dysfunction (PGD), posttransplant lung function, freedom from chronic lung allograft dysfunction (CLAD), and overall survival. PGD did not differ between the groups. Posttransplant lung function was comparable after bilateral lung transplantation, but seemed worse after DCD3 single lung transplantation. The incidence of CLAD (p = 0.17) nor the freedom from CLAD (p = 0.36) nor the overall survival (p = 0.40) were significantly different between both groups. The presented multicenter results are derived from a national context where one third of the lung transplantations are performed with DCD3 lungs. We conclude that the long-term outcome after lung transplantation with DCD3 donors is similar to that of DBD donors and that DCD3 donation can substantially enlarge the donor pool.
      PubDate: 2017-05-30T10:01:24.624707-05:
      DOI: 10.1111/ajt.14339
  • Vascularized Composite Allograft Donation and Transplantation: A Survey of
           Public Attitudes in the United States
    • Authors: J. R. Rodrigue; D. Tomich, A. Fleishman, A. K. Glazier
      Pages: 2687 - 2695
      Abstract: Vascularized composite allograft (VCA) transplantation has emerged as a groundbreaking surgical intervention to return identity and function following traumatic injury, congenital deformity, or disfigurement. While public attitudes toward traditional organ/tissue donation are favorable, little is known about attitudes toward VCA donation and transplantation. A survey was conducted of 1485 U.S. residents in August 2016 to assess VCA donation attitudes. Participants also completed the Revised Health Care System Distrust Scale. Most respondents were willing to donate hands/forearms (67.4%) and legs (66.8%), and almost half (48.0%) were willing to donate the face. Three-quarters (74.4%) of women were willing to donate the uterus; 54.4% of men were willing to donate the penis. VCA donation willingness was more likely among whites and Hispanics (p < 0.001), registered organ/tissue donors (p < 0.001), and those with less health care system distrust (p < 0.001) and media exposure to VCA transplantation (p = 0.003). Many who opposed VCA donation expressed concerns about psychological discomfort, mutilation, identity loss, and the reaction of others to seeing familiar body parts on a stranger. Attitudes toward VCA donation are favorable overall, despite limited exposure to VCA messaging and confusion about how VCA donation occurs. These findings may help guide the development and implementation of VCA public education campaigns.
      PubDate: 2017-05-15T08:25:39.936885-05:
      DOI: 10.1111/ajt.14302
  • New Insights Into the Alleged Kidney Donor Profile Index Labeling Effect
           on Kidney Utilization
    • Authors: D. E. Stewart; V. C. Garcia, M. I. Aeder, D. K. Klassen
      Pages: 2696 - 2704
      Abstract: The Kidney Donor Profile Index (KDPI) became a driving factor in deceased donor kidney allocation on December 4, 2014, with the implementation of the kidney allocation system (KAS). On April 20, 2016, the annual recalibration of the Kidney Donor Risk Index into KDPI was incorrectly programmed in DonorNet, resulting in erroneously high KDPI values, by between 1 and 21 percentage points (e.g. actual KDPI of 70% was displayed as 86%). The error was corrected on May 19, 2016,
      PubDate: 2017-07-17T08:20:32.490846-05:
      DOI: 10.1111/ajt.14379
  • Impact of Left Ventricular Diastolic Dysfunction on Lung Transplantation
           Outcome in Patients With Pulmonary Arterial Hypertension
    • Authors: A. Avriel; A. H. Klement, S. R. Johnson, M. Perrot, J. Granton
      Pages: 2705 - 2711
      Abstract: Diastolic dysfunction may influence perioperative outcome, early graft function, and long-term survival. We compared the outcomes of double lung transplantation (DLTx) for patients with pulmonary arterial hypertension (PAH) with preoperative left ventricular (LV) diastolic dysfunction with the outcomes of patients without diastolic dysfunction. Of 116 consecutive patients with PAH (who underwent transplantation between January 1995 and December 2013), 44 met our inclusion and exclusion criteria. Fourteen (31.8%) patients with diastolic dysfunction pretransplantation had a higher body mass index (29 [IQR 21.5–32.6] vs 22.4 [IQR 19.9–25.3] kg/m2) and mean pulmonary arterial pressure (54.6 ± 10 mmHg vs 47 ± 11.3 mmHg) and right atrial pressure (16.5 ± 5.2 mmHg vs 10.6 ± 5.2 mmHg). The patients received extracorporeal life support more frequently (33% vs 7% [p = 0.02]), had worse APACHE II scores (21.7 ± 7.4 vs 15.3 ± 5.3 [p = 0.02]), and a trend toward worse ventilator-free days (2.5 [IQR 6.5–32.5] vs 17 [IQR 3–23] [p = 0.08]). There was no effect on development of primary graft dysfunction or intensive care unit/hospital survival. One-year survival was worse (hazard ratio [HR] 4.45, 95% confidence interval [CI] 1.3–22, p = 0.02). Diastolic dysfunction was the only variable that correlated with overall survival (HR 5.4, 95% CI 1.3–22, p = 0.02). Diastolic dysfunction leads to early postoperative morbidity and worse survival in patients with PAH after DLTx.
      PubDate: 2017-07-03T14:30:21.731804-05:
      DOI: 10.1111/ajt.14352
  • Lessons Learned: Early Termination of a Randomized Trial of Calcineurin
           Inhibitor and Corticosteroid Avoidance Using Belatacept
    • Authors: K. A. Newell; A. K. Mehta, C. P. Larsen, P. G. Stock, A. B. Farris, S. G. Mehta, D. Ikle, B. Armstrong, Y. Morrison, N. Bridges, M. Robien, R. B. Mannon
      Pages: 2712 - 2719
      Abstract: The intent of this National Institutes of Health–sponsored study was to compare a belatacept-based immunosuppressive regimen with a maintenance regimen of tacrolimus and mycophenolate. Nineteen primary, Epstein–Barr virus–immune renal transplant recipients with a negative cross-match were randomized to one of three groups. All patient groups received perioperative steroids and maintenance mycophenolate mofetil. Patients in groups 1 and 2 were induced with alemtuzumab and maintained on tacrolimus or belatacept, respectively. Patients in group 3 were induced with basiliximab, received 3 mo of tacrolimus, and maintained on belatacept. There was one death with a functioning allograft due to endocarditis (group 1). There were three graft losses due to vascular thrombosis (all group 2) and one graft loss due to glomerular disease (group 1). Biopsy-proven acute cellular rejection was more frequent in the belatacept-treated groups, with 10 treated episodes in seven participants compared with one episode in group 1; however, estimated GFR was similar between groups at week 52. There were no episodes of posttransplant lymphoproliferative disorder or opportunistic infections in any group. Protocol enrollment was halted prematurely because of a high rate of serious adverse events. Such negative outcomes pose challenges to clinical investigators, who ultimately must weigh the risks and benefits in randomized trials.
      PubDate: 2017-07-03T09:30:24.656398-05:
      DOI: 10.1111/ajt.14377
  • Modeling the Iatrogenic Pancreatic Cancer Risk After Islet
           Autotransplantation in Mouse
    • Authors: E. Dugnani; V. Pasquale, D. Liberati, A. Citro, E. Cantarelli, S. Pellegrini, P. Marra, T. Canu, G. Balzano, M. Scavini, A. Esposito, C. Doglioni, L. Piemonti
      Pages: 2720 - 2727
      Abstract: Iatrogenic pancreatic cancer metastasis after islet infusion is a potential risk of islet autotransplantation performed after pancreatectomy. To model this risk, islets and/or pancreatic exocrine clusters obtained from a genetically engineered mouse model for pancreatic ductal adenocarcinoma (the LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre, termed KPC mouse) were transplanted via the portal vein in syngeneic wild type (WT) severely diabetic recipients in the following treatment groups: group A (n = 11) received KPC exocrine clusters in volume equal to 250 islet equivalents (IEQs); group B (n = 12) received 250 WT IEQs mixed with KPC exocrine clusters (1:1 volume ratio); group C (n = 5) received 250 KPC IEQs, and group D (n = 7) received 250 WT IEQs. The incidence of hepatic metastasis was assessed by magnetic resonance imaging and histology over the 13 months of follow-up. Overall survival was not different in the four groups. No mice developed liver metastases during the follow-up. Two mice developed spontaneous tumors: a liver hepatocellular tumor in group A and a malignant lymphoma in group D. Islets and/or exocrine clusters obtained by KPC mouse, a model that develops pancreatic cancer with 100% penetrance, do not retain the same risk of tumor development when transplanted via the portal vein in a syngeneic diabetic recipient.
      PubDate: 2017-06-12T13:25:38.218776-05:
      DOI: 10.1111/ajt.14360
  • Blood Chimerism in Dizygotic Monochorionic Twins During 5 Years
    • Authors: M. H. Dziegiel; M. H. Hansen, S. Haedersdal, A. N. Barrett, K. Rieneck, K. M. Main, A. T. Hansen, F. B. Clausen
      Pages: 2728 - 2732
      Abstract: Dizygotic monochorionic twin pregnancies can result in blood chimerism due to in utero twin-to-twin exchange of stem cells. In this case, we examined the proportion of allogeneic red blood cells by flow cytometry and the proportion of allogeneic nucleated cells by digital polymerase chain reaction at 7 months and again at 5 years. We found an increase in the proportion of allogeneic cells from 63% to 89% in one twin, and a similar increase in autologous cells in the other twin from 57% to 84%. A paradigm for stem cell therapy could be modeled on this case: induction of tolerance and chimerism by antenatal transfusion of donor stem cells. The procedure would hold the promise of transplantation and tolerance induction without myeloablative conditioning for inheritable benign hematological diseases such as sickle cell disease and thalassemia.
      PubDate: 2017-05-11T09:10:53.769253-05:
      DOI: 10.1111/ajt.14318
  • Solid Organ Transplant–Transmitted Tuberculosis Linked to a Community
           Outbreak — California, 2015
    • Authors: A. Kay; P. M. Barry, P. Annambhotla, C. Greene, M. Cilnis, P. Chin-Hong, N. Arger, L. McNitt, N. Neidlinger, N. Shah, S. V. Basavaraju, M. Kuehnert, T. Shaw
      Pages: 2733 - 2736
      Abstract: This report highlights the association of donor-derived tuberculosis with a community outbreak of tuberculosis.
      PubDate: 2017-09-28T09:36:39.958322-05:
      DOI: 10.1111/ajt.14471
  • Acute allograft dysfunction with abnormal ultrasound findings in a renal
           transplant recipient
    • Authors: Carrie A. Carson; Aisling E. Courtney, Jennifer A. McCaughan
      Pages: 2737 - 2739
      PubDate: 2017-09-28T09:36:37.887879-05:
      DOI: 10.1111/ajt.14438
  • Kidney Paired-Donation Program Versus Global Kidney Exchange in India
    • Authors: V. Kute; R. M. Jindal, N. Prasad
      Pages: 2740 - 2741
      PubDate: 2017-05-22T10:40:23.860183-05:
      DOI: 10.1111/ajt.14324
  • Comment: Kidney Exchange to Overcome Financial Barriers to Kidney
    • Authors: L. S. Baines; R. M. Jindal
      Pages: 2742 - 2742
      PubDate: 2017-05-15T10:00:54.974864-05:
      DOI: 10.1111/ajt.14325
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