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Publisher: John Wiley and Sons   (Total: 1589 journals)

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Showing 1 - 200 of 1589 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: 47, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 52, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 165, 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: 6, 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: 7, 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: 14, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 27, 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: 51, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 14, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 268, 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: 7, 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: 21)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 13)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 10)
African Development Review     Hybrid Journal   (Followers: 33, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 16, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 11, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 3, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 16, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 45, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 32, 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: 51, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 148, 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: 92, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 29, 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: 276, 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: 137, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 9, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 18)
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: 225)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 222, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 41, 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: 8, 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: 89, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 49, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 8, 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: 70, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 207, 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: 5)
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: 245, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 52, 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: 15)
Asia & the Pacific Policy Studies     Open Access   (Followers: 16)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 319, 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: 6, 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: 15, 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: 6, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 14, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 3, 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: 47, 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: 5, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 31, 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: 72, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 12, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 21, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 36, 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: 11, 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: 10, 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: 4, 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: 37, 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: 142, 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: 38, 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: 6, 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: 243, 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  [1589 journals]
  • Campath, calcineurin inhibitor reduction and chronic allograft nephropathy
           (the 3C Study) – results of a randomized controlled clinical trial
    • Authors: Richard Haynes; Lisa Blackwell, Natalie Staplin, William G Herrington, Jonathan Emberson, Parminder K Judge, Benjamin C Storey, Martin J Landray, Paul N Harden, Colin Baigent, Peter Friend
      Abstract: Calcineurin inhibitors (CNI e.g. tacrolimus) reduce short-term kidney transplant failure, but chronic nephrotoxicity may contribute to late transplant loss. Elective conversion to inhibitors of the mammalian target of rapamycin pathway (mTOR e.g. sirolimus) might avoid long-term CNI renal damage and improve outcomes. The 3C Study was a pragmatic randomized controlled trial comprising sequential randomizations between alemtuzumab and basiliximab induction therapy (at the time of surgery) and between tacrolimus and sirolimus maintenance therapy at 6-months post-transplant. The primary outcome of this analysis was estimated glomerular filtration rate (eGFR) at 18 months after maintenance therapy randomization. 197 patients were assigned sirolimus-based and 197 to tacrolimus-based therapy. Allocation to sirolimus had no significant effect on eGFR at 18 months: baseline-adjusted mean (SE) eGFR 53.7 (0.9) mL/min/1.73m2 in the sirolimus group versus 54.6 (0.9) mL/min/1.73m2 in the tacrolimus group (p=0.50). Biopsy-proven acute rejection (29 [14.7%]) vs 6 [3.0%]; p
      PubDate: 2017-12-11T02:55:25.223351-05:
      DOI: 10.1111/ajt.14619
  • Comparative evaluation of simple indices using a single fasting blood
           sample to estimate beta cell function after islet transplantation
    • Authors: Justyna E. Gołębiewska; Julia Solomina, Celeste Thomas, Mark Kijek, Piotr Bachul, Lindsay Basto, Karolina Golab, Ling-jia Wang, Natalie Fillman, Martin Tibudan, Kamil Cieply, Luis Philipson, Alicja Dębska-Ślizień, J.Michael Millis, John Fung, Piotr Witkowski
      Abstract: Six single fasting blood sample based indices: Secretory Unit of Islet Transplant Objects (SUITO), Transplant Estimated Function (TEF), Homeostasis Model Assessment (HOMA)2-B%, C-peptide/glucose ratio (CP/G), C-peptide/glucose creatinine ratio (CP/GCr) and BETA-2 score, were compared against commonly used 90-min mixed meal tolerance test (MMTT) serum glucose and beta-score to assess which of them best recognizes the state of acceptable blood glucose control without insulin supplementation after islet allotransplantation (ITx). We also tested if the indices could identify the success of ITx based on the Igls classification of beta-cell graft function. We analyzed values from 47 MMTT tests in 4 patients with up to 140 months follow-up and from 54 MMTT tests in 13 patients with up to 42 months follow-up.SUITO, CP/G, HOMA2-B% and BETA-2 correlated well with the 90-min glucose of the MMTT and beta-score (r 0.54-0.76), whereas CP/GCr showed a modest performance (r 0.41-0.52) while TEF showed little correlation. BETA-2 and SUITO were the best identifiers and predictors of the need for insulin support, glucose intolerance and ITx success (p
      PubDate: 2017-12-08T03:20:30.815672-05:
      DOI: 10.1111/ajt.14620
  • Islet Damage during Isolation as Assessed by miRNAs and the Correlation of
           miRNA Levels with Posttransplant Outcome in Islet Autotransplantation
    • Authors: Prathab Balaji Saravanan; Mazhar A. Kanak, Charles A Chang, Carly Darden, Gumpei Yoshimatsu, Michael C. Lawrence, Bashoo Naziruddin
      Abstract: High-quality pancreatic islets are essential for better posttransplant endocrine function in total pancreatectomy with islet autotransplantation (TPIAT), yet stress during the isolation process affects quality and yield. We analyzed islet-enriched miRNAs -375 and -200c released during isolation to assess damage and correlated the data with posttransplant endocrine function. The absolute concentration of miR-375, miR-200c, and C-peptide was measured in various islet isolation steps, including digestion, dilution, recombination, purification, and bagging, in 12 cases of TPIAT. Posttransplant glycemic control was monitored through C-peptide, hemoglobin A1cs, insulin requirement, and SUITO index. The amount of miR-375 released was significantly higher during enzymatic digestion following by the islet bagging (P < 0.001). MiR-200c mirrored these changes, albeit at lower concentrations. In contrast, the C-peptide amount was significantly higher in the purification and bagging steps (P < 0.001). Lower amounts of miR-375 were associated with a lower 6-month insulin requirement (P = 0.03) and lower hemoglobin A1c (P = 0.04). Measurement of the absolute quantity of miRNAs 375 and 200c released during islet isolation is a useful tool to assess islet damage. The quantity of released miRNA is indicative of posttransplant endocrine function in TPIAT patients.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-06T02:15:23.335533-05:
      DOI: 10.1111/ajt.14615
  • Mood, Body Image, Fear of Kidney Failure, Life Satisfaction, and
           Decisional Stability Following Living Kidney Donation: Findings from the
           KDOC Study
    • Authors: J R Rodrigue; J D Schold, P Morrissey, J Whiting, J Vella, L K Kayler, D Katz, J Jones, B Kaplan, A Fleishman, M Pavlakis, D A Mandelbrot,
      Abstract: Prior studies demonstrate that most living kidney donors (LKDs) report no adverse psychosocial outcomes; however, changes in psychosocial functioning at the individual donor level have not been routinely captured. We studied psychosocial outcomes pre-donation and at 1, 6, 12, and 24 months post-donation in 193 LKDs and 20 healthy controls (HCs). There was minimal to no mood disturbance, body image concerns, fear of kidney failure, or life dissatisfaction, indicating no incremental changes in these outcomes over time and no significant differences between LKDs and HCs. The incidence of any new-onset adverse outcomes post-donation was as follows: mood disturbance (16%), fear of kidney failure (21%), body image concerns (13%), and life dissatisfaction (10%). Multivariable analyses demonstrated LKDs with more mood disturbance symptoms, higher anxiety about future kidney health, low body image, and low life satisfaction prior to surgery were at highest risk of these same outcomes post-donation. Importantly, some LKDs showed improvement in psychosocial functioning from pre- to post-donation. Findings support the balanced presentation of psychosocial risks to potential donors as well as the development of a donor registry to capture psychosocial outcomes beyond the mandatory two-year follow-up period in the USA.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-05T10:50:21.603494-05:
      DOI: 10.1111/ajt.14618
  • Isolated v-lesion in kidney transplant recipients: Characteristics,
           association with DSA and histological follow-up
    • Authors: Marion Rabant; Fanny Boullenger, Viviane Gnemmi, Gaëlle Pellé, François Glowacki, Alexandre Hertig, Isabelle Brocheriou, Caroline Suberbielle, Jean-Luc Taupin, Dany Anglicheau, Christophe Legendre, Jean-Paul Duong Van Huyen, David Buob
      Abstract: Isolated v-lesion (IvL) represents a rare and challenging situation in renal allograft biopsies because it is unknown whether IvL truly represents rejection, antibody- or T cell-mediated, or not.This multicentric retrospective study describes the clinicopathological features of IvL with an emphasis on the Donor Specific Antibodies (DSA) status, histological follow-up, and graft survival. Inclusion criteria were the presence of v-lesion with minimal interstitial (i≤1) and microvascular inflammation (g+ptc≤1). C4d positive biopsies were excluded.We retrospectively found 33 IvL biopsies in 33 patients, mainly performed in the early post-transplant period (median time 27 days) and clinically indicated in 66.7%. A minority of recipients (5/33, 15.2%) had DSA at the time of biopsy. IvL was treated by anti-rejection therapy in 21 cases (63.6%), whereas 12 (36.4%) were untreated. 70% of untreated patients and 66% of treated patients showed favorable histological evolution on subsequent biopsy. Kidney graft survival in IvL was significantly higher than in a matched cohort of antibody-mediated rejection with arteritis.In conclusion, IvL is not primarily antibody-mediated and may show a favorable evolution. The heterogeneity of IvL pathophysiology on early biopsies should prompt DSA testing as well as close clinical and histological follow-up in all patients with IvL.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-05T10:45:40.429972-05:
      DOI: 10.1111/ajt.14617
  • Novel Approaches to Antifungal Therapy
    • Authors: George R. Thompson; Thomas F. Patterson
      Abstract: Invasive fungal infections remain a major cause of morbidity and mortality in the solid organ transplant population. Non-Aspergillus infections are of particular concern due to the reduced antifungal susceptibility of many of these fungi (Scedopsorium, Lomentospora, Fusarium etc), the difficulty in distinguishing these organisms from Aspergillus spp based on histopathology alone, and the higher associated mortality observed with these organisms. Current treatment options for these fungi are limited, and voriconazole is the most commonly recommended primary agent1, 2 with combination therapy (terbinafine or an echinocandin) also recommended by some experts.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-05T10:45:38.336819-05:
      DOI: 10.1111/ajt.14616
  • Multi-level factors are associated with immunosuppressant nonadherence in
           heart transplant recipients: the international bright study
    • Authors: Kris Denhaerynck; Lut Berben, Fabienne Dobbels, Cynthia L. Russell, Marisa G Crespo-Leiro, Alain Jean Poncelet, Sabina De Geest,
      Abstract: Factors at the level of family/healthcare worker-, organization- and system are neglected in medication nonadherence research in heart transplantation (HTx). The four-continent, eleven-country cross-sectional BRIGHT study used multi-staged sampling to examine 36 HTx centers, including 36 HTx directors, 100 clinicians, and 1397 patients. Nonadherence to immunosuppressants–defined as any deviation in taking or timing adherence and/or dose reduction–was assessed using the BAASIS® interview. Guided by the Integrative Model of Behavioral Prediction and Bronfenbrenner's ecological model, we analyzed factors at these multiple levels using sequential logistic regression analysis (6 blocks). The nonadherence prevalence was 34.1%. Six multi-level factors were associated independently (either positively or negatively) with nonadherence: patient level: barriers to taking immunosuppressants (OR: 11.48); smoking (OR:2.19); family/healthcare provider level: frequency of having someone to help patients read health-related materials (OR:0.85); organization level: clinicians reporting non-adherent patients were targeted with adherence interventions (OR: 0.66); pick-up of medications at physician's office (OR: 2.31); and policy level: monthly out-of-pocket costs for medication (OR: 1.16). Factors associated with nonadherence are evident at multiple levels. Improving medication nonadherence requires addressing not only the patient, but also family/healthcare provider, organization, and policy levels.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-05T02:00:57.519023-05:
      DOI: 10.1111/ajt.14611
  • Duodenal graft complications requiring duodenectomy after pancreas and
           pancreas-kidney transplantation
    • Authors: Erica Pieroni; Niccolò Napoli, Carlo Lombardo, Piero Marchetti, Margherita Occhipinti, Carla Cappelli, Davide Caramella, Giovanni Consani, Gabriella Amorese, Maurizio De Maria, Fabio Vistoli, Ugo Boggi
      Abstract: Duodenal graft complications are poorly reported complications of pancreas transplantation that can result in graft loss. Excluding patients with early graft failure, after a median follow-up period of 126 months (range 23-198) duodenectomy was required in 14 of 312 pancreas transplants (4.5%). All patients were insulin-independent at the time of diagnosis. Reasons for duodenectomy included delayed duodenal graft perforation (n=10, 71.5%) and refractory duodenal graft bleeding (n=4, 28.5%).In patients with duodenal graft bleeding, a total duodenectomy was performed. In patients with duodenal graft perforation, preservation of a duodenal segment was possible in 5 patients but completion duodenectomy was necessary in one patient. After total duodenectomy, immediate enteric duct drainage was feasible in seven patients. In two patients, a pancreaticocutaneous fistula was created that was subsequently converted to enteric drainage in one patient. In the other patient, enteric fistulization occurred as a consequence of silent pressure perforation of the draining catheter on the ascending colon.After a mean follow-up period of 52 months (21-125), all patients were alive, well, and insulin-independent.An aggressive and timely surgical approach may permit graft rescue in patients with severe duodenal graft complications occurring after pancreas transplantation. Generalization of these results remains to be established.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-04T09:27:18.141876-05:
      DOI: 10.1111/ajt.14613
  • Response to: Renal Allograft Histology at 10 Years After Transplantation
           in the Tacrolimus Era: Evidence of Pervasive Chronic Injury
    • Authors: Renaud Snanoudj; Christophe Legendre
      Abstract: We read with great interest the study by Stegall (1) and colleagues regarding histological lesions observed on 10-year protocol biopsies in 145 kidney transplant recipients who had received standard-of-care immunosuppression (tacrolimus and mycophenolic acid). Of interest, these biopsies displayed severe arteriolar hyalinosis in 66% of cases.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-01T07:35:22.82334-05:0
      DOI: 10.1111/ajt.14612
  • Personal Viewpoint: The Bridge Between Transplantation and Regenerative
           Medicine. Beginning a New Banff Classification of Tissue Engineering
    • Authors: K. Solez; K. C. Fung, K. A. Saliba, V. L. C. Sheldon, A. Petrosyan, L. Perin, J. F. Burdick, W. H. Fissell, A. J. Demetris, L. D. Cornell
      Abstract: The science of regenerative medicine is arguably older than transplantation - the first major textbook was published in 1901 - and a major regenerative medicine meeting took place in 1988, three years before the first Banff transplant pathology meeting. However, the subject of regenerative medicine/tissue engineering pathology has never received focused attention. Defining and classifying tissue engineering pathology is long overdue. In the next decades, the field of transplantation will enlarge at least tenfold, through a hybrid of tissue engineering combined with existing approaches to lessening the organ shortage. Gradually transplantation pathologists will become tissue-(re-) engineering pathologists with enhanced skill sets to address concerns involving the use of bioengineered organs. We outline ways of categorizing abnormalities in tissue-engineered organs through traditional light microscopy or other modalities including biomarkers. We propose creating a new Banff Classification of tissue engineering pathology to standardize and assess de novo bioengineered solid organs transplantable success in vivo. We recommend constructing a framework for a classification of tissue engineering pathology now with interdisciplinary consensus discussions to further develop and finalize the classification at future Banff Transplant Pathology meetings, in collaboration with the human cell atlas project. A possible nosology of pathologic abnormalities in tissue-engineered organs is suggested.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-01T02:55:52.478568-05:
      DOI: 10.1111/ajt.14610
  • The causes, significance and consequences of inflammatory fibrosis in
           kidney transplantation: The Banff i-IFTA lesion
    • Authors: Brian J. Nankivell; Meena Shingde, Karen L. Keung, Caroline L-S. Fung, Richard J. Borrows, Philip J. O'Connell, Jeremy R. Chapman
      Abstract: Inflammation within areas of interstitial fibrosis and tubular atrophy (i-IFTA) is associated with adverse outcomes in kidney transplantation.We evaluated i-IFTA in 429 indication- and 2052 protocol-biopsies from a longitudinal cohort of 362 kidney-pancreas recipients to determine its prevalence, time-course, and relationships with T cell mediated rejection (TCMR), immunosuppression, and outcome.Sequential histology demonstrated that i-IFTA was preceded by cellular interstitial inflammation, and followed by IF/TA. The prevalence and intensity of i-IFTA increased with developing chronic fibrosis, and correlated with inflammation, tubulitis and immunosuppression era (P
      PubDate: 2017-12-01T02:55:37.402393-05:
      DOI: 10.1111/ajt.14609
  • Sex-Based Disparities in Delisting for Being “Too Sick” for
           Liver Transplantation
    • Authors: Giuseppe Cullaro; Monika Sarkar, Jennifer C. Lai
      Abstract: Women with cirrhosis awaiting liver transplantation (LT) experience higher rates of waitlist mortality than men – it is unknown if practices surrounding delisting for being “too sick” for LT contribute to this disparity beyond death alone. We conducted an analysis of patients listed for LT in the UNOS/OPTN network not receiving exception points from 5/1/07 to 7/1/14 with a primary outcome of delisting with removal codes of “too sick” or “medically unsuitable.” A total of 44,388 patients were included, 4,458 were delisted for being “too sick” for LT. Delisting was more frequent in women (11v.9%, p
      PubDate: 2017-12-01T02:00:26.956259-05:
      DOI: 10.1111/ajt.14608
  • Triptolide Inhibits Donor Specific Antibody Production and Attenuates
           Mixed Antibody-Mediated Renal Allograft Injury
    • Authors: Daqiang Zhao; Siwen Li, Tao Liao, Yuan Wei, Mingyu Liu, Fei Han, Zihuan Luo, Xiaonan Liu, Qiquan Sun
      Abstract: Donor specific antibodies (DSAs) are major mediators of renal allograft injury, and strategies to inhibit DSA are important in promoting long term graft survival. Triptolide exhibits a wide spectrum of anti-inflammatory and immuno- suppressive activities, and in autoimmune diseases it inhibits autoantibody levels. In this study, we investigated the suppressive role of triptolide in the generation of donor specific antibodies in transplant recipients. We found that triptolide treatment of skin allograft recipients in the mouse significantly suppressed the development of circulating anti-donor specific IgG and effectively alleviated DSAs-mediated renal allograft injury, which led to prolonged allograft survival. In vitro studies revealed that triptolide inhibited the differentiation of B cells into CD138+CD27++ plasma cells, reduced the levels of IgA, IgG and IgM secreted by plasma cells, and repressed somatic hypermutation and class switch recombination of B cells. Moreover, triptolide treated recipients showed reduced number of B cells, plasma cells and memory B cells in spleens and decreased number of T, B, NK cells and macrophages infiltrating in grafts. These findings highlight the importance of triptolide in suppressing DSAs and establish triptolide as a novel therapeutic agent for antibody-mediated allograft rejection.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-27T02:30:21.344378-05:
      DOI: 10.1111/ajt.14602
  • Review: The transcripts associated with organ allograft rejection
    • Authors: Philip F Halloran; Jeffery M. Venner, Katelynn Madill-Thomsen, Gunilla Einecke, Michael Parkes, Luis G. Hidalgo, Konrad S. Famulski
      Abstract: The molecular mechanisms operating in human organ transplant rejection are best inferred from the mRNAs expressed in biopsies because the corresponding proteins often have low expression and short half-lives, while small non-coding RNAs lack specificity. Associations should be characterized in a population that rigorously identifies T cell-mediated (TCMR) and antibody-mediated rejection (ABMR). This is best achieved in kidney transplant biopsies, but the results are generalizable to heart, lung, or liver transplants. Associations can be universal (all rejection), TCMR-selective, or ABMR-selective, with universal being strongest and ABMR-selective weakest. Top universal transcripts are IFNG-inducible (e.g. CXCL11; IDO1, WARS) or shared by effector T cells (ETCs) and NK cells (e.g. KLRD1, CCL4). TCMR-selective transcripts are expressed in activated ETCs (e.g. CTLA4, IFNG); activated (e.g. ADAMDEC1) or IFNG-induced macrophages (e.g. ANKRD22). ABMR-selective transcripts are expressed in NK cells (e.g. FGFBP2, GNLY) and endothelial cells (e.g. ROBO4, DARC). Transcript associations are highly reproducible between biopsy sets when the same rejection definitions, case mix, algorithm, and technology are applied, but exact ranks will vary. Previously published rejection-associated transcripts resemble universal and TCMR-selective transcripts due to incomplete representation of ABMR. Rejection-associated transcripts are never completely rejection-specific because they are shared with the stereotyped response-to-injury and innate immunity.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-25T11:15:28.865361-05:
      DOI: 10.1111/ajt.14600
  • Comprehensive Review of Post-Organ Transplant Hematologic Cancers
    • Authors: Vikas R. Dharnidharka
      Abstract: A higher risk for a variety of cancers is among the major complications of post-transplant immunosuppression. In this part of a continuing series on cancers post-transplant, this review focuses on the hematologic cancers after solid organ transplant. Post-transplant lymphoproliferative disorders (PTLDs), which comprise the great majority of hematologic cancers, represent a spectrum of conditions that include, but are not limited to, the Hodgkin and non-Hodgkin lymphomas. The oncogenic Epstein-Barr virus is a key pathogenic driver in many PTLD cases, through known and unknown mechanisms. The other hematologic cancers include leukemias and plasma cell neoplasms (multiple myeloma and plasmacytoma). Clinical features vary across malignancies and location. Preventive screening strategies have been attempted mainly for PTLDs. Treatments include the chemotherapy regimens for the specific cancers, but also include reduction of immunosuppression, rituximab and other therapies.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-25T11:15:26.965672-05:
      DOI: 10.1111/ajt.14603
  • Early Barriers to Neonatal Porcine Islet Engraftment in a Dual Transplant
    • Authors: K P Samy; R P Davis, Q Gao, B M Martin, M Song, J Cano, A B Farris, A McDonald, E K Gall, C R Dove, F V Leopardi, T How, K D Williams, G R Devi, B H Collins, A D Kirk
      Abstract: Porcine islet xenografts have the potential to provide an inexhaustible source of islets for β cell replacement. Proof-of-concept has been established in nonhuman primates. However, significant barriers to xenoislet transplantation remain, including, the poorly understood instant blood mediated inflammatory reaction (IBMIR), and a thorough understanding of early xeno-specific immune responses. A paucity of data exist comparing xeno-specific immune responses to allo-islet responses in primates. We recently developed a dual islet transplant model, which enables direct histological comparison of early engraftment immunobiology. In this study, we investigate early immune responses to neonatal porcine islet (NPI) xenografts compared to rhesus islet allografts at 1 hour, 24 hours, and 7 days. Within the first 24 hours after intraportal infusion, we identified greater apoptosis (caspase 3 activity and TUNEL positive cells) of NPIs when compared to alloislets (AIs). Macrophage infiltration was significantly greater at 24 hours compared with 1 hour in both NPI (WT) and AIs. At 7 days, IgM and macrophages were highly specific for NPIs (GTKO) compared to AIs. These findings demonstrate an augmented macrophage and antibody response towards xenografts compared to allografts. These data may inform future immune or genetic manipulations required to improve xenoislet engraftment.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-25T11:15:24.808902-05:
      DOI: 10.1111/ajt.14601
  • Improvement in Pancreas Transplant Evaluation and Surgical Volume Using a
           Multidisciplinary Approach
    • Authors: Joseph R. Scalea; Samuel Sultan, Elizabeth Lamos, Stephen T. Bartlett, Rolf N. Barth
      Abstract: Pancreas numbers are down: Pancreas transplantation is the only long-term treatment for diabetes which restores glucose homeostasis, without the risks of hypoglycemia.1-3 Further, receiving a simultaneous pancreas kidney (SPK) transplant improves life expectancy over kidney transplantation alone.4,5 Despite this, the total number of pancreas transplants in the United States has decreased since 2006. Experts in the field recently reported that, while this drop in volume is multifactorial, the lack of a steady referral source is partly to blame.1This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-22T12:51:19.510128-05:
      DOI: 10.1111/ajt.14598
  • Shipping Living Donor Kidneys and Transplant Recipient Outcomes
    • Authors: Eric Treat; Eric K H Chow, John D Peipert, Amy Waterman, Lorna Kwan, Allan B Massie, Alvin G. Thomas, Mary Grace Bowring, David Leeser, Stuart Flechner, Marc L Melcher, Sandip Kapur, Dorry L Segev, Jeffrey Veale
      Abstract: Kidney paired donation (KPD) is an important tool to facilitate living donor kidney transplantation (LDKT). Concerns remain over prolonged cold ischemia times (CIT) associated with shipping kidneys long distances through KPD. We examined the association between CIT and delayed graft function (DGF), allograft survival, and patient survival for 1,267 shipped and 205 non-shipped/internal KPD LDKTs facilitated by the National Kidney Registry in the United States from 2008-2015, compared to 4,800 unrelated, non-shipped, non-KPD LDKTs. Shipped KPD recipients had a median CIT of 9.3 hours (range = 0.25 to 23.9 hours), compared to 1.0 hour for internal KPD transplants and 0.93 hours for non-KPD LDKTs. Each hour of CIT was associated with a 5% increased odds of DGF (adjusted odds ratio: 1.05, 95% CI: 1.02-1.09, p0.9). This study of KPD-facilitated LDKTs found no evidence that long CIT is a concern for reduced graft or patient survival. Studies with longer follow-up are needed to refine our understanding of the safety of shipping donor kidneys through KPD.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-22T10:05:23.048278-05:
      DOI: 10.1111/ajt.14597
  • Thymic function is a major determinant of antibody-mediated rejection
           onset in heart transplantation
    • Authors: A. Sannier; N. Stroumza, G. Caligiuri, M. Le Borgne-Moynier, F. Andreata, J. Senemaud, L. Louedec, G. Even, A. T. Gaston, C. Deschildre, A. Couvelard, P. Ou, R. Cheynier, P. Nataf, R. Dorent, A. Nicoletti
      Abstract: Thymic function progressively decreases with age but may be boosted in certain circumstances. We questioned whether heart transplantation was such a situation and whether the thymic function was related to the onset of rejection. Twenty-eight antithymocyte globulin-treated heart transplant recipients were included. Patients diagnosed for an antibody-mediated rejection on endomyocardial biopsy had higher proportion of circulating recent thymic emigrant CD4+ T cells and T cell receptor excision circle levels than other transplanted subjects. Thymus volume and density, assessed by computed tomography in a subset of patients, was also higher in patient experiencing antibody-mediated rejection. We demonstrate that thymic function is a major determinant of antibody-mediated rejection onset and question whether thymectomy could be a prophylactic strategy to prevent alloimmune humoral responses.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-21T11:45:33.251899-05:
      DOI: 10.1111/ajt.14595
  • Islet allo-autotransplantation: allogeneic pancreas transplantation
           followed by transplant pancreatectomy and islet transplantation
    • Authors: M.F. Nijhoff; J. Dubbeld, A.R. van Erkel, P.J.M van der Boog, T.J. Rabelink, M.A. Engelse, E.J.P de Koning
      Abstract: Simultaneous pancreas/kidney (SPK) transplantation is an important treatment option for patients with type 1 diabetes (T1D) and end stage renal disease (ESRD). Due to complications, in up to 10% of cases allograft pancreatectomy is necessary shortly after transplantation. Usually the donor pancreas is discarded. Here we report on a novel procedure to rescue endocrine tissue after allograft pancreatectomy. A 39-year-old woman with T1D and ESRD who had received an SPK transplantation required emergency allograft pancreatectomy due to bleeding at the vascular anastomosis. Islets were isolated from the removed pancreas allograft and almost 480,000 islet equivalents were infused into the portal vein. The patient recovered fully. After three months near-normal mixed meal test (fasting glucose 7.0 mmol/L, 2-hour glucose 7.5 mmol/L, maximal stimulated C-peptide 3.25 nmol/L, without insulin use in the preceding 36 hours) was achieved. HbA1c while taking a low dose of long-acting insulin was 32.7 mmol/mol Hb (5.3%). When a donor pancreas is lost after transplantation, rescue beta cell therapy by islet allo-autotransplantation enables optimal use of scarce donor pancreata to optimize glycemic control without additional HLA allo-antigen exposure.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-21T11:45:19.621809-05:
      DOI: 10.1111/ajt.14593
  • Invited response to Recurrence of oxalate nephropathy after isolated
           kidney transplantation for primary hyperoxaluria type 2
    • Authors: Tsering Dhondup; Elizabeth C. Lorenz, Dawn S. Milliner, John C. Lieske
      Abstract: We read with interest the letter from Dr. Del Bello and colleagues regarding our recent case report of successful combined liver/kidney transplantation in a patient with primary hyperoxaluria type 2 (PH2) that resulted in normalization of urine and plasma oxalate levels. They describe a patient with PH2 who, unfortunately, developed renal allograft failure 6 months after a kidney alone transplant (1). The reasons for renal allograft failure in their patient are not entirely clear.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-21T09:20:19.93494-05:0
      DOI: 10.1111/ajt.14596
  • American Journal of Transplantation: Volume 17, Number 12, December 2017
    • Abstract: On the cover this month: A central tenet of live donor organ transplantation is to preserve donor health. However, the practice of organ donation continues to change with advances in medical care and a general aging of the population. This has sparked a move to better capture donor outcomes and facilitate evidence-based donation decisions. This month, AJT presents three articles relevant to this movement. Kasiske et al (page 3040) present a view from the Scientific Registry of Transplant Recipients, detailing a new registry to document organ donor outcomes. Henderson et al (page 3131) examine the generally incomplete compliance with new mandates to document early donor outcomes, and Debra Sudan places these efforts in context in a thoughtful editorial, distinguishing mandated short-term reporting as perhaps separate from actionable assessment of long-term donor outcomes. Also this month, we provide three timely and wide-reaching reviews on palliative care (Wentlandt et al, page 3008), mechanical circulatory support (Cai et al, page 3020) and the proteasome (Eskandari et al, page 3033). Cover image by Megan Llewellyn, Duke University Department of Surgery.
      PubDate: 2017-11-16T12:55:39.39432-05:0
      DOI: 10.1111/ajt.14552
  • Paneth and Intestinal Stem Cells Preserve their Functional Integrity
           during Worsening of Acute Cellular Rejection in Small Bowel
    • Authors: M. Pucci Molineris; V. Gonzalez Polo, Federico Perez, D. Ramisch, M. Rumbo, G. E. Gondolesi, D. Meier
      Abstract: Graft survival after small bowel transplantation remains impaired due to acute cellular rejection (ACR), the leading cause of graft loss. Although it was shown that the number of enteroendocrine progenitor cells in intestinal crypts was reduced during mild ACR, no results of Paneth and intestinal stem cells localized at the crypt bottom have been shown so far. Therefore, we wanted to elucidate integrity and functionality of the Paneth and stem cells during different degrees of ACR, and to assess whether these cells are the primary targets of the rejection process. We compared biopsies from ITx patients with no, mild or moderate ACR by immunohistochemistry and quantitative PCR. Our results show that numbers of Paneth and stem cells remain constant in all study groups, whereas the transit-amplifying zone is the most impaired zone during ACR. We detected an unchanged level of antimicrobial peptides in Paneth cells and similar numbers of Ki-67+ IL-22R+ stem cells revealing cell functionality in moderate ACR samples. We conclude that Paneth and stem cells are not primary target cells during ACR. IL-22R+ Ki-67+ stem cells might be an interesting target cell population for protection and regeneration of the epithelial monolayer during/after a severe ACR in ITx patients.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-15T05:56:31.455894-05:
      DOI: 10.1111/ajt.14592
  • Late graft failure after kidney transplantation as the consequence of late
           versus early events
    • Authors: Robert S. Gaston; Ann Fieberg, Lawrence Hunsicker, Bertram L. Kasiske, Robert Leduc, Fernando G. Cosio, Sita Gourishankar, Joseph Grande, Roslyn B. Mannon, David Rush, Michael J. Cecka, John Connett, Arthur J. Matas
      Abstract: Beyond the first posttransplant year, 3% of kidney transplants fail annually. In a prospective, multicenter cohort study, we tested the relative impact of early versus late events on risk of long-term death-censored graft failure (DCGF). In grafts surviving at least 90 days, early events (acute rejection [AR] and delayed graft function [DGF] before day 90) were recorded; serum creatinine (Cr) at day 90 was defined as baseline. Thereafter, a 25% rise in serum Cr or new onset proteinuria triggered graft biopsy (index biopsy, IBx), allowing comparison of risk of DCGF associated with early events (AR, DGF, baseline serum Cr>2.0 mg/dL) to that associated with later events (IBx). Among 3678 patients followed 4.7±1.9 years, 753(20%) had IBx at a median of 15.3 months posttransplant. Early AR (HR=1.77, p
      PubDate: 2017-11-15T05:50:23.835037-05:
      DOI: 10.1111/ajt.14590
  • Comments on “Impact of spontaneous donor hypothermia on graft outcomes
           after kidney transplantation”
    • Authors: Claus Niemann; Kristine Broglio, Darren Malinoski
      Abstract: Using a retrospective cohort that was part of a donor intervention trial published in 2009 1, Schnuelle et al report in this issue that spontaneous hypothermia in deceased organ donors resulted in decreased recipient renal delayed graft function2. Allograft survival was not statistically significantly different during long-term follow up. While spontaneous hypothermia is likely a distinct physiologic process compared to targeted mild hypothermia, as in our previously reported randomized controlled trial3, the findings of the current retrospective study further confirm our impression that therapeutic mild hypothermia and deceased organ donor intervention research, in general, hold tremendous potential for addressing the ongoing shortage of organs available for transplantation.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-15T05:50:21.850221-05:
      DOI: 10.1111/ajt.14591
  • Primary Graft Dysfunction after Heart Transplantation: Incidence, Trends
           and Associated Risk Factors
    • Authors: Alina Nicoara; David Ruffin, Mary Cooter, Chetan B. Patel, Annemarie Thompson, Jacob Schroeder, Mani A. Daneshmand, Adrian F. Hernandez, Joseph G. Rogers, Mihai V. Podgoreanu, Madhav Swaminathan, Adam Kretzer, Mark Stafford-Smith, Carmelo A. Milano, Raquel R. Bartz
      Abstract: Changes in heart transplant (HT) donor and recipient demographics may influence the incidence of primary graft dysfunction (PGD). We conducted a retrospective study to evaluate PGD incidence, trends, and associated risk factors by analyzing consecutive adult patients who underwent HT between January 2009 and December 2014 at our institution. Patients were categorized as having PGD using the International Society of Heart and Lung Transplantation defined criteria. Variables, including clinical and demographic characteristics of donors and recipients, were selected to assess their independent association with PGD. A time-trend analysis was performed over the study period. Three-hundred seventeen patients met inclusion criteria. Left ventricular PGD, right ventricular PGD or both were observed in 99 (31%) patients. Risk factors independently associated with PGD included ischemic time, recipient African-American race, and recipient amiodarone treatment. Over the study period, there was no change in the PGD incidence, however there was an increase in the recipient pre-transplant use of amiodarone. The rate of 30-day mortality was significantly elevated in those with PGD vs those without PGD (6.06% vs 0.92%, P=0.01). Despite recent advancements, incidence of PGD remains high. Understanding associated risk factors may allow for implementation of targeted therapeutic interventions.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-14T11:35:27.229389-05:
      DOI: 10.1111/ajt.14588
  • Heme Oxygenase-1 Regulates Sirtuin-1 – Autophagy Pathway in Liver
           Transplantation: From Mouse-to-Human
    • Authors: Kojiro Nakamura; Shoichi Kageyama, Shi Yue, Jing Huang, Takehiro Fujii, Bibo Ke, Rebecca A. Sosa, Elaine F. Reed, Nakul Datta, Ali Zarrinpar, Ronald W. Busuttil, Jerzy W. Kupiec-Weglinski
      Abstract: Liver ischemia-reperfusion injury (IRI) represents a major risk factor of early graft dysfunction and a key obstacle to expanding the donor pool in orthotopic liver transplantation (OLT). Although graft autophagy is essential for resistance against hepatic IRI, its significance in clinical OLT remains unknown. Despite recent data identifying heme oxygenase-1 (HO-1) as a putative autophagy inducer, its role in OLT and interactions with Sirtuin-1 (SIRT1), a key autophagy regulator, have not been studied. We aimed to examine HO-1 mediated autophagy induction in human OLT and in a murine OLT model with extended (20h) cold storage, as well as to analyze the requirement for SIRT1 in autophagy regulation by HO-1. Fifty-one hepatic biopsies from OLT patients were collected under an IRB protocol two hours after portal reperfusion, followed by Western blot analyses. High HO-1 levels correlated with well-preserved hepatocellular function and enhanced SIRT1/LC3B expression. In mice, HO-1 overexpression by genetically-modified HO-1 macrophage therapy, was accompanied by decreased OLT damage, increased SIRT1/LC3B expression, whereas adjunctive inhibition of SIRT1 signaling diminished HO-1 mediated hepatoprotection and autophagy induction. Our translational study confirms the clinical relevance of HO-1 cytoprotection and identifies SIRT1-mediated autophagy pathway as a new essential regulator of HO-1 function in IR-stressed OLT.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-14T10:17:02.172312-05:
      DOI: 10.1111/ajt.14586
  • IL-7 Receptor Heterogeneity as a Mechanism for Repertoire Change during
           Post-Depletional Homeostatic Proliferation and its Relation to
           Costimulation Blockade–Resistant Rejection
    • Authors: He Xu; Victoria A. Bendersky, Todd V. Brennan, Jaclyn R. Espinosa, Allan D. Kirk
      Abstract: Kidney transplant patients treated with belatacept without depletional induction experience higher rates of acute rejection compared to patients treated with conventional immunosuppression. Costimulation blockade-resistant rejection (CoBRR) is associated with terminally differentiated T cells. Alemtuzumab induction and belatacept/sirolimus immunotherapy effectively prevents CoBRR. We hypothesized that cells in late phases of differentiation would be selectively less capable of repopulating post-depletion than more naïve phenotypes, providing a potential mechanism by which lymphocyte depletion and repopulation could reduce the risk of CoBRR. Lymphocytes from 20 recipients undergoing alemtuzumab-induced depletion and belatacept/sirolimus immunosuppression were studied longitudinally for markers of maturation (CCR7, CD45RA, CD57, PD1), recent thymic emigration (CD31), and the interleukin-7 receptor-α (IL-7Rα). Serum was analyzed for IL-7. Alemtuzumab induction produced profound lymphopenia followed by repopulation, during which naïve IL-7Rα+CD57-PD1- cells progressively became the predominant subset. This did not occur in a comparator group of 10 patients treated with conventional immunosuppression. Serum from depleted patients showed markedly elevated IL-7 levels posttransplantation. Sorted CD57-PD1- cells demonstrated robust proliferation in response to IL-7, while more differentiated cells proliferated poorly. These data suggest that differences in IL-7-dependent proliferation is one exploitable mechanism distinguishing CoB-sensitive and CoB-resistant T cell populations to reduce the risk of CoBRR. ClinicalTrials. gov - NCT00565773This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-14T10:15:48.013744-05:
      DOI: 10.1111/ajt.14589
  • Outcomes of Donation after Circulatory Death kidneys undergoing
           Hypothermic Machine Perfusion following Static Cold Storage: A UK
           population-based cohort study
    • Authors: Kamlesh Patel; Jay Nath, James Hodson, Nick Inston, Andrew Ready
      Abstract: Evidence is currently lacking regarding the outcomes of kidneys undergoing Hypothermic Machine Perfusion (HMP) in the UK. Using the National Health Service Blood and Transplant database, the authors compared outcomes for recipients of single organ Donation after Circulatory Death (DCD) kidneys preserved with HMP to those using only static cold storage (SCS).Between 2007 and 2015, HMP was used in 19.1% (864/4,529) of kidneys. Rates of delayed graft function (DGF) were significantly lower in organs preserved with HMP than for SCS (34.2% vs. 42.0%, p
      PubDate: 2017-11-14T10:05:35.107369-05:
      DOI: 10.1111/ajt.14587
  • The First Case of Ischemia-free Organ Transplantation in Humans: A Proof
           of Concept
    • Authors: Xiaoshun He; Zhiyong Guo, Qiang Zhao, Weiqiang Ju, Dongping Wang, Linwei Wu, Lu Yang, Fei Ji, Yunhua Tang, Zhiheng Zhang, Shanzhou Huang, Linhe Wang, Zebin Zhu, Kunpeng Liu, Yanling Zhu, Yifang Gao, Wei Xiong, Ming Han, Bing Liao, Maogen Chen, Yi Ma, Xiaofeng Zhu, Wenqi Huang, Changjie Cai, Xiangdong Guan, Xian Chang Li, Jiefu Huang
      Abstract: Ischemia and reperfusion injury (IRI) is an inevitable event in conventional organ transplant procedure and is associated with significant mortality and morbidity post-transplantation. We hypothesize that IRI is avoidable if the blood supply for the organ is not stopped, thus resulting in optimal transplant outcomes. Here we described the first case of a novel procedure called ischemia-free organ transplantation (IFOT) for patients with end-stage liver disease. The liver graft with severe macrovesicular steatosis was donated from a 25-year-old man. The recipient was a 51-year-old man with decompensated liver cirrhosis and hepatocellular carcinoma. The graft was procured, preserved and implanted under continuous normothermic machine perfusion. The recipient did not suffer post-reperfusion syndrome or vasoplegia after revascularization of the allograft. The liver function test and histological study revealed minimal hepatocyte, biliary epithelium and vascular endothelium injury during preservation and post-transplantation. The inflammatory cytokine levels were much lower in IFOT than those in conventional procedure. Key pathways involved in IRI were not activated after allograft revascularization. No rejection, vascular or biliary complications occurred. The patient was discharged on day 18 post-transplantation. This marks the first case of IFOT in humans, offering opportunities to optimize transplant outcomes and maximize donor organ utilization.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-10T21:25:42.354801-05:
      DOI: 10.1111/ajt.14583
  • Erratum
    • PubDate: 2017-11-09T14:20:20.730199-05:
      DOI: 10.1111/ajt.14575
  • Erythropoietic protoporphyria in an adult with sequential liver and
           hematopoietic stem cell transplantation: A case report
    • Authors: Annika L. Windon; Rashmi Tondon, Nathan Singh, Samir Abu-Gazala, David L. Porter, J. Eric Russell, Colleen Cook, Elaine Lander, Georgeine Smith, Kim M. Olthoff, Abraham Shaked, Maarouf Hoteit, Emma E. Furth, Marina Serper
      Abstract: Erythropoieitic protoporphyria (EPP) is a rare inherited disorder of the heme biosynthesis pathway resulting in the accumulation of protoporphyrins in the blood, erythrocytes, and other tissues. Because of a gene mutation in the FECH gene, ferrochelatase, the enzyme involved in the final step of heme synthesis, is deficient in these patients. While the major symptom of this disorder is photosensitivity, rarely, it can cause progressive liver disease requiring liver transplantation (LT). However, LT is not curative and only bone marrow transplantation (BMT) can correct the underlying enzymatic defect. Since liver disease results from accumulation of protoporphyrin in the liver, LT without hematopoietic stem cell transplant leaves the new liver at risk for similar EPP-related damage. A handful of pediatric cases undergoing sequential LT and stem cell transplantation have been described in the literature, however, to date none have been described in detail in adults. We report a case of an adult male with EPP and liver failure who successfully underwent a sequential liver and hematopoietic stem cell transplant (HSCT).This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-08T08:41:05.104058-05:
      DOI: 10.1111/ajt.14581
  • Screening for Zika Virus in Deceased Organ Donors in Florida
    • Authors: J Simkins; S Anjan, J A Morillas-Rodriguez, S R Greissman, L M Abbo, J F Camargo, P Ruiz, R Vianna, G Guerra, S Salama, M I Morris
      Abstract: Zika virus (ZIKV) cases have been detected across the United States (US) and locally acquired cases have been reported in Florida. Currently, there are no ZIKV screening guidelines and no data on the incidence among organ donors in the US. This retrospective study was conducted at Jackson Memorial-Miami Transplant Institute. Positive ZIKV tests in local deceased organ donors were investigated from 6/2016 to 1/2017. We evaluated demographics and risk factors for ZIKV infection among organ donors and transplant outcomes among recipients of donors with positive ZIKV testing. 142 donors were analyzed. 10% had traveled to ZIKV-endemic countries and 19% had outdoor occupations. Only 3% had positive ZIKV IGG. None had a positive ZIKV IGM or PCR. ZIKV-positive donors were more likely to have traveled to ZIKV-endemic countries (50% vs. 9%, P=0.05). The kidneys from a ZIKV-positive donor were transplanted in our hospital with no 6-month rejection, graft failure or death in the recipients. Our study demonstrated a low prevalence of ZIKV among deceased donors in our community. Despite local ZIKV transmission, ZIKV was more common in donors who traveled to ZIKV-endemic countries. This cohort demonstrated excellent outcomes in recipients of ZIKV IGG-positive donors. However, larger studies are needed.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-08T08:40:47.196536-05:
      DOI: 10.1111/ajt.14582
  • Salvage therapy with topical posaconazole in lung transplant recipients
           with invasive scedosporium infection
    • Authors: Amparo Solé; Ana A. García-Robles, Carlos Jordá, Enrique Cases Viedma, Nuria Mancheño, José Luis Poveda-Andrés, Juan Pablo Reig Mezquida, Javier Pemán
      Abstract: Scedosporium is an important pathogen in cystic fibrosis (CF) and post-transplant, but it rarely causes invasive infection. Treatment remains challenging, particularly due to the inherent resistance to multiple antifungal agents. We present three complicated invasive tracheobronchial and lung Scedosporium apiospermum infections following lung transplant. In two of three cases, the infection was clinically and radiologically cured with frequent cleansing bronchoscopies, combining triazole with terbinafine therapy and nebulized posaconazole. These cases highlight the importance of adjunctive nebulized therapy in addition to prolonged triazole treatment to manage complex invasive Scedosporium infections in immunosuppressed patients. Posaconazole (PSZ) was delivered during the bronchoscopy procedure through intrabronchial administration, whereas an eFlow rapid® device was used for nebulized therapy. Topical posaconazole was well tolerated in two patients, with only a slight cough during administrations; the third patient suffered local irritation with poor tolerance, which led to its withdrawal. This is the first report on compassionate use of topical posaconazole as salvage therapy for resistant mold infections in lung transplantation recipients. These three cases represent the entire experience using this approach; no additional patients have received this therapy due to not having received any additional cases of Scedosporium tracheobronchitis.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-08T08:40:41.749785-05:
      DOI: 10.1111/ajt.14580
  • Emergency Department Utilization among Kidney Transplant Recipients in the
           United States
    • Authors: Brendan P. Lovasik; Rebecca Zhang, Jason M. Hockenberry, Justin D. Schrager, Stephen O. Pastan, Andrew B. Adams, Sumit Mohan, Christian P. Larsen, Rachel E. Patzer
      Abstract: Patients with End Stage Renal Disease (ESRD) use the emergency department (ED) at a 6-fold higher rate than U.S. adults. No national studies have described ED utilization rates among kidney transplant (KTx) recipients, and the factors associated with higher ED utilization. We examined a cohort of 132,725 adult KTx recipients in the United States Renal Data System (2005-2013). ED visits, hospitalization, and outpatient nephrology visits were obtained from Medicare claims databases. Nearly half (46.1%) of KTx recipients had at least one ED visit (1.61 ED visits/patient year) and 39.7% of ED visits resulted in hospitalization in the first year post-transplant. ED visit rate was high in the first 30 days (5.26 visits/person year (PY)), but declined substantially thereafter (1.81 visits/ PY in months 1-3; 1.13 visits/PY in months 3-12 post-transplant). ED visit rates were higher in the first 30 days vs. dialysis patients, but less than half the rate thereafter. Female sex, public insurance, medical comorbidities, longer pre-transplant dialysis vintage, and delayed graft function were associated with higher ED utilization in the first year post-KTx. Policies and strategies addressing potentially preventable ED visits should be promoted to help improve patient care and increase efficient utilization of ED resources.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-08T08:40:39.540979-05:
      DOI: 10.1111/ajt.14578
  • Turn Down for What' Patient Outcomes Associated with Declining
           Increased Infectious Risk Kidneys
    • Authors: Mary G. Bowring; Courtenay M. Holscher, Sheng Zhou, Allan B. Massie, Jacqueline Garonzik-Wang, Lauren M. Kucirka, Sommer E. Gentry, Dorry L. Segev
      Abstract: Transplant candidates who accept a kidney labeled increased risk for disease transmission (IRD) accept a low risk of window period infection, yet those who decline must wait for another offer that might harbor other risks or never even come. To characterize survival benefit of accepting IRD kidneys, we used 2010-2014 SRTR data to identify 104,998 adult transplant candidates who were offered IRD kidneys that were eventually accepted by someone; the median (IQR) KDPI of these kidneys was 30 (16-49). We followed patients from the offer decision until death or end-of-study. After 5 years, only 31.0% of candidates who declined IRDs later received non-IRD DDKTs; the median KDPI of these non-IRD kidneys was 52, compared to 21 of the IRDs they had declined. After a brief risk period in the first 30 days following IRD acceptance [aHR accept vs decline:, p=0.008] (absolute mortality 0.8% vs. 0.4%), those who accepted IRDs were at 33% lower risk of death 1-6 months post-decision [aHR 0.500.670.90, p=0.006], and at 48% lower risk of death beyond 6 months post-decision [aHR 0.460.520.58, p
      PubDate: 2017-11-08T08:40:37.209966-05:
      DOI: 10.1111/ajt.14577
  • The Utilisation of Boari Flap Vesicocalycostomy (BFV) for Salvage Repair
           of Kidney Transplant Ureteric Injury after Robotic Radical Prostatectomy
    • Authors: Ziting Wang; Wy Keat Tay, Lincoln Guan Lin Tan, Ho Yee Tiong
      Abstract: The prevalence of prostate carcinoma in kidney transplant male recipients approach 1.1% (1). Despite increasing reports of RRP performed for ageing kidney transplant recipients, there are no publications addressing post-operative complications including transplant ureteric injuries(2-3). These complications are potentially devastating and difficult to salvage, as illustrated by the following report of an opportunistic utilisation of BFV to manage complete ureteric obstruction of the transplant kidney after a RRP.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-08T08:40:34.629603-05:
      DOI: 10.1111/ajt.14579
  • Functional status, healthcare utilization, and the costs of liver
    • Authors: Marina Serper; Therese Bittermann, Michael Rossi, David S. Goldberg, Arwin M. Thomasson, Kim M. Olthoff, Abraham Shaked
      Abstract: The Model for End-stage Liver Disease (MELD) score predicts higher transplant healthcare utilization and costs; however, the independent contribution of functional status towards costs is understudied. The study objective was to evaluate the association between functional status, as measured by Karnofsky Performance Status (KPS), and liver transplant (LT) costs in the first post-transplant year. In a cohort of 598 LT recipients from 7/1/2009-11/30/2014, multivariable models assessed associations between KPS and outcomes. LT recipients needing full assistance (KPS 10-40%) versus being independent (KPS 80-100%) were more likely to be discharged to a rehabilitation facility after LT (22% vs 3%) and be re-hospitalized within the first post-transplant year (78% vs 57%), all p
      PubDate: 2017-11-08T08:40:33.554798-05:
      DOI: 10.1111/ajt.14576
  • Erratum
    • PubDate: 2017-11-01T12:35:20.468232-05:
      DOI: 10.1111/ajt.14502
  • Postoperative Cognitive Dysfunction and Mortality following Lung
    • Authors: P J Smith; J A Blumenthal, B M Hoffman, R.Duane Davis, S M Palmer
      Abstract: Preliminary evidence suggests that postoperative cognitive dysfunction (POCD) is common following lung transplantation. The impact of POCD on clinical outcomes has yet to be studied. The association between POCD and longer term survival was therefore examined in a pilot study of post-transplant survivors.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-31T06:35:18.438724-05:
      DOI: 10.1111/ajt.14570
  • NAT Testing in Recipients of Hepatitis C Aviremic Donor Organs
    • Authors: Lena Sibulesky; Ajit P Limaye
      Abstract: As outcomes of transplantation have improved, the number of transplant candidates listed for deceased donor transplantation has increased significantly over the years. Organ shortage is one of the greatest challenges facing the field of organ transplantation. Until recently, organs from donors who tested for hepatitis C virus (HCV) have been used exclusively in recipients with chronic HCV infection or were discarded at a high rate.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-31T06:30:31.145796-05:
      DOI: 10.1111/ajt.14568
  • Reply to Christakoudi and Hernandez-Fuentes: We agree—Let's move on
    • Authors: Adam Asare; Sai Kanaparthi, Noha Lim, Kenneth A. Newell, Laurence A. Turka
      Abstract: In regard to the Letter to the Editor by Christakoudi and Hernandez-Fuentes (1), we can only say that we generally agree with all the points the authors make, and are at a loss as to how the cautionary statements included in our manuscript (2) are at odds with the concerns they raise. Obviously we agree with their title “Lack of adjustment for confounding [sic] could lead to misleading conclusions.” The authors write as if we are advocating clinical usage of a signature based solely on the data presented in our paper.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-31T06:30:19.6454-05:00
      DOI: 10.1111/ajt.14569
  • Anti-CD47 Monoclonal Antibody Therapy Reduces Ischemia-Reperfusion Injury
           of Renal Allografts in a Porcine Model of Donation after Cardiac Death
    • Authors: Min Xu; Xuanchuan Wang, Babak Banan, Danielle L. Chirumbole, Sandra Garcia-Aroz, Aparna Balakrishnan, Deepak K. Nayak, Zhengyan Zhang, Jianluo Jia, Gundumi A. Upadhya, Joseph P. Gaut, Ronald Hiebsch, Pamela T. Manning, Ningying Wu, Yiing Lin, William C. Chapman
      Abstract: We investigated whether blockade of the CD47 signaling pathway could reduce ischemia-reperfusion injury (IRI) of renal allografts donated after cardiac death (DCD) in a porcine animal model of transplantation. Renal allografts were subjected to 30 min of warm ischemia, 3.5 hours of cold ischemia and then perfused with a humanized anti-CD47 monoclonal antibody (CD47mAb) in the treatment group or HTK solution in the control group (n=4/group). The animals were euthanized 5 days after transplantation. At the time of reperfusion, indocyanine green-based in vivo imaging showed that CD47mAb-treated organs had greater and more uniform reperfusion. On post-transplant days 3-5, the treatment group had lower values compared to the control for creatinine and blood urea nitrogen. Histological examination of allograft tissues showed a significant decrease of acute tubular injury in the CD47mAb-treated group compared to control. Compared to the control group, CD47mAb treatment significantly decreased genes expression related to oxidative stress (sod-1, gpx-1, and txn), the inflammatory response (il-2, il-6, inf-g and tgf-b), as well as reduced protein levels of BAX, Caspase-3, MMP2, and MMP9. These data demonstrate that CD47mAb blockade decreases IRI and subsequent tissue injury in DCD renal allografts in a large animal transplant model.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-31T06:25:23.135039-05:
      DOI: 10.1111/ajt.14567
  • The effect of match-run frequencies on the number of transplants and
           waiting times in kidney exchange
    • Authors: Itai Ashlagi; Adam Bingaman, Maximilien Burq, Vahideh Manshadi, David Gamarnik, Cathi Murphey, Alvin E. Roth, Marc L. Melcher, Michael A. Rees
      Abstract: Numerous kidney exchange (kidney paired donor (KPD)) registries in the U.S have gradually shifted to high frequency match-runs, raising the question of whether this harms the number of transplants. We conduct simulations using clinical data from two KPD registries—the Alliance for Paired Donation, which runs multi-hospital exchanges, and Methodist San Antonio, which runs single center exchanges–to study how the frequency of match-runs impacts the number of transplants and the average waiting times. We simulate the options facing each of the two registries by repeated resampling from their historical pools of patient-donor pairs and non-directed donors, with arrival and departure rates corresponding to the historical data. We find that longer intervals between match-runs do not increase the total number of transplants, and that prioritizing highly sensitized patients is more effective than waiting longer between match-runs for transplanting highly sensitized patients. While we do not find that frequent match-runs result in fewer transplanted pairs we do find that increasing arrival rates of new pairs improves both the fraction of transplanted pairs and waiting times.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-31T06:20:20.812839-05:
      DOI: 10.1111/ajt.14566
  • T cell-mediated rejection is a major determinant of inflammation in
           scarred areas in kidney allografts
    • Authors: Carmen Lefaucheur; Clément Gosset, Marion Rabant, Denis Viglietti, Jérôme Verine, Olivier Aubert, Kevin Louis, Denis Glotz, Christophe Legendre, Jean-Paul Duong Van Huyen, Alexandre Loupy
      Abstract: Inflammation in fibrosis areas (i-IF/TA) of kidney allografts is associated with allograft loss; however, its diagnostic significance remains to be determined. We investigated the clinico-histologic phenotype and determinants of i-IF/TA in a prospective cohort of 1,539 kidney recipients undergoing evaluation of i-IF/TA and tubulitis in atrophic tubules (t-IF/TA) on protocol allograft biopsies performed at one year post-transplantation. We considered donor, recipient and transplant characteristics, immunosuppression and histological diagnoses in 2,260 indication biopsies performed within the first year post-transplantation. 946 (61.5%) patients presented interstitial fibrosis (IF/TA Banff grade>0) at one year post-transplant, among whom 394 (41.6%) showed i-IF/TA. i-IF/TA correlated with concurrent t-IF/TA (P
      PubDate: 2017-10-31T01:45:23.611624-05:
      DOI: 10.1111/ajt.14565
  • Brief Report: Factors Associated with Perceived Donation-Related Financial
           Burden among Living Kidney Donors
    • Authors: Jessica M. Ruck; Courtenay M. Holscher, Tanjala S. Purnell, Allan B. Massie, Macey L. Henderson, Dorry L. Segev
      Abstract: The perception of living kidney donation-related financial burden affects willingness to donate and the experience of donation, yet no existing tools identify donors at higher risk of perceived financial burden. We sought to identify characteristics that predicted higher risk of perceived financial burden. We surveyed 51 LKDs who donated 01/2015-3/2016 about socioeconomic characteristics, pre-donation cost concerns, and perceived financial burden. We tested associations between both self-reported and ZIP code-level characteristics and perceived burden using Fisher's exact test and bivariate modified Poisson regression. Donors who perceived donation-related financial burden were less likely to have an income above their ZIP code median (14% vs. 72%, p=0.006); however, they were more likely than donors who did not perceive burden to rent their home (57% vs. 16%, p=0.03), have an income
      PubDate: 2017-10-25T06:55:53.540231-05:
      DOI: 10.1111/ajt.14548
  • Immunoisolation of Murine Islet Allografts in Vascularized Sites Through
           Conformal Coating with Polyethylene Glycol
    • Authors: Vita Manzoli; Chiara Villa, Allison L Bayer, Laura Morales, R Damaris Molano, Yvan Torrente, Camillo Ricordi, Jeffrey A Hubbell, Alice A Tomei
      Abstract: Islet encapsulation may allow transplantation without immunosuppression but thus far islets in large microcapsules transplanted in the peritoneal cavity failed to reverse diabetes in humans. We showed that islet transplantation in confined well-vascularized sites like the epididymal fat pad (EFP) improved graft outcomes, but only conformal coated (CC) islets can be implanted in these sites in curative doses. Here, we showed that CC using polyethylene glycol (PEG) and alginate (ALG) was not immunoisolating because of its high permselectivity and strong allogeneic T cell responses. We refined the CC composition and explored PEG and islet-like extracellular matrix (MG) islet encapsulation (PEG MG) to improve capsule immunoisolation by decreasing its permselectivity and immunogenicity while allowing physiological islet function. Though diabetes reversal efficiency of allogeneic but not syngeneic CC islets was lower than naked islets, we showed that CC (PEG MG) islets from fully MHC-mismatched Balb/c mice supported long-term (> 100 days) survival after transplantation into diabetic C57BL/6 recipients in the EFP site (750-1000 IEQ / mouse) in absence of immunosuppression. Lack of immune cell penetration and T cell allogeneic priming was observed. These studies support the use of CC (PEG MG) for islet encapsulation and transplantation in clinically-relevant sites without chronic immunosuppression.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-25T06:50:33.027671-05:
      DOI: 10.1111/ajt.14547
  • Recurrence of oxalate nephropathy after isolated kidney transplantation
           for primary hyperoxaluria type 2
    • Authors: Arnaud Del Bello; Olivier Cointault, Audrey Delas, Nassim Kamar
      Abstract: We read with interest the case report by Dhondup et al., who suggest that combined liver–kidney transplantation should be considered for patients with end-stage chronic kidney disease (CKD) caused by primary hyperoxaluria type 2 (PH2). This is in contrast to isolated kidney transplantation that is usually proposed (1).This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-25T06:50:18.59646-05:0
      DOI: 10.1111/ajt.14550
  • Longitudinal Assessment of T Cell Inhibitory Receptors in Liver Transplant
           Recipients and their association with Post-transplant Infections
    • Authors: Krupa R. Mysore; Rafik M. Ghobrial, Sunil Kannanganat, Laurie J. Minze, Edward A. Graviss, Duc T. Nguyen, Katherine K. Perez, Xian C. Li
      Abstract: Current immunosuppression regimens in organ transplantation primarily inhibit T cells. However, T cells are also critical in protective immunity, especially in immune compromised patients. In this study, we examined the association of T cell dysfunction, as marked by expression of T cell exhaustion molecules, and post-transplant infections in a cohort of liver transplant patients. We focused on Programmed Death 1(PD-1) and T-cell Ig-and mucin-domain molecule3 (Tim-3) which are potent co-inhibitory receptors, and their persistent expression often leads to T cell dysfunction and compromised protective immunity. We found that patients with the highest expression of PD-1+Tim-3+ T cells in the memory compartment before transplantation had increased incidence of infections after liver transplantation, especially within the first 90 days. Longitudinal analysis in the first year showed a strong association between variability of PD-1 and Tim-3 expression by T cells and infectious episodes in transplant patients. Furthermore, T cells that expressed PD-1 and Tim-3 had a significantly reduced capacity in producing IFN-γ in vitro, and this reduced IFN-γ production could be partially reversed by blocking PD-1 and Tim-3. Interestingly, the percentage of Foxp3+ Tregs in liver transplant patients was stable in the study period. We concluded that the functional status of T cells before and after liver transplantation, as shown by PD-1 and Tim-3 expression, may be valuable in prognosis and management of post-transplant infections.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-25T06:45:26.965678-05:
      DOI: 10.1111/ajt.14546
  • Validation of the Prognostic Power of the RETREAT Score for Hepatocellular
           Carcinoma Recurrence Using the UNOS Database
    • Authors: Neil Mehta; Jennifer L. Dodge, John P. Roberts, Francis Y. Yao
      Abstract: A recent multi-center study developed and validated a novel prognostic index “Risk Estimation of Tumor Recurrence After Transplant (RETREAT)”, which incorporates alpha-fetoprotein (AFP) at liver transplant (LT), microvascular invasion, and the sum of the largest viable tumor and number of tumors on explant. We now aim to evaluate RETREAT in the United Network for Organ Sharing (UNOS) database in hepatocellular carcinoma (HCC) patients meeting Milan criteria by imaging who underwent LT from 2012-2014. On explant (n=3276), 13% had microvascular invasion, 30% had no viable tumor, and 15% exceeded Milan criteria. Post-LT survival at 3 years decreased with increasing RETREAT score: 91% for a score of 0, 80% for a score of 3, and 58% for a score>5 (p5 (p
      PubDate: 2017-10-25T06:45:19.15015-05:0
      DOI: 10.1111/ajt.14549
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Xenotransplantation: Time to Get Excited'
    • Authors: Lara C. Pullen
      Pages: 2995 - 2996
      Abstract: This month, “The AJT Report” focuses on new efforts and investments warranting a resurgence of interest in xenotransplantation as a way to solve the organ shortage. We also present key results from the National Academies of Sciences, Engineering, and Medicine's new donor intervention report.
      PubDate: 2017-11-16T12:55:36.026215-05:
      DOI: 10.1111/ajt.14553
  • Stealing Tregs’ Identity (by Deleting NF-κB)
    • Authors: Maria-Luisa Alegre
      Pages: 2997 - 2997
      Abstract: The same transcription factor NF-κB enables the opposing effects of Tconv activation and Treg maintenance/suppression by accessing different areas of open chromatin in each cell type.
      PubDate: 2017-11-16T12:55:42.352883-05:
      DOI: 10.1111/ajt.14554
  • Living donor follow-up: Unfunded mandates and the Hippocratic oath where
           perfect may be the enemy of good'
    • Authors: D. Sudan
      Pages: 3006 - 3007
      Abstract: The author advances a concern that the currently mandated living donor follow-up at 6 months, 1 year, and 2 years postdonation adds unnecessary burden on transplant centers and organ donors, without improving outcome or better identifying donor health issues, and that this leads to the lower compliance Henderson et al discuss (page 3131).
      PubDate: 2017-09-07T08:05:26.045901-05:
      DOI: 10.1111/ajt.14442
  • Mechanical Circulatory Support in the Treatment of Advanced Heart Failure
    • Authors: A. W. Cai; S. Islam, S. R. Hankins, W. Fischer, H. J. Eisen
      Pages: 3020 - 3032
      Abstract: According to the Centers for Disease Control, heart failure (HF) remains a pervasive condition with high morbidity and mortality, affecting 5.8 million people in the United States and 23 million worldwide. For patients with refractory end-stage HF, heart transplantation is the “gold standard” for definitive treatment. However, the demand for heart transplantation has consistently exceeded the availability of donor hearts, with approximately 2331 orthotopic heart transplantations performed in the United States in 2015 despite an estimated 100 000 to 250 000 patients with New York Heart Association class IIIB or IV symptoms that are refractory to medical treatment, making such patients potential transplant candidates. As such, the need for mechanical circulatory support (MCS) to treat patients with end-stage HF has become paramount. In this review, we focus on the history, advancements, and current use of durable MCS device therapy in the treatment of advanced heart failure.
      PubDate: 2017-07-24T14:35:22.319315-05:
      DOI: 10.1111/ajt.14403
  • 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
      Pages: 3033 - 3039
      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 major histocompatibility complex 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.
      PubDate: 2017-08-30T10:35:35.644879-05:
      DOI: 10.1111/ajt.14435
  • The Living Donor Collective: A Scientific Registry for Living Donors
    • Authors: B. L. Kasiske; S. K. Asrani, M. A. Dew, M. L. Henderson, C. Henrich, A. Humar, A. K. Israni, K. L. Lentine, A. J. Matas, K. A. Newell, D. LaPointe Rudow, A. B. Massie, J. J. Snyder, S. J. Taler, J. F. Trotter, A. D. Waterman,
      Pages: 3040 - 3048
      Abstract: In the setting of an overall decline in living organ donation and new questions about long-term safety, a better understanding of outcomes after living donation has become imperative. Adequate information on outcomes important to donors may take many years to ascertain and may be evident only by comparing large numbers of donors with suitable controls. Previous studies have been unable to fully answer critical questions, primarily due to lack of appropriate controls, inadequate sample size, and/or follow-up duration that is too short to allow detection of important risks attributable to donation. The Organ Procurement and Transplantation Network does not follow donors long term and has no prospective control group with which to compare postdonation outcomes. There is a need to establish a national living donor registry and to prospectively follow donors over their lifetimes. In addition, there is a need to better understand the reasons many potential donors who volunteer to donate do not donate and whether the reasons are justified. Therefore, the US Health Resources and Services Administration asked the Scientific Registry of Transplant Recipients to establish a national registry to address these important questions. Here, we discuss the efforts, challenges, and opportunities inherent in establishing the Living Donor Collective.
      PubDate: 2017-06-22T13:05:23.555522-05:
      DOI: 10.1111/ajt.14365
  • Regulatory T Cells Promote Natural Killer Cell Education in Mixed Chimeras
    • Authors: B. Mahr; N. Pilat, S. Maschke, N. Granofszky, C. Schwarz, L. Unger, K. Hock, A. M. Farkas, C. Klaus, H. Regele, T. Wekerle
      Pages: 3049 - 3059
      Abstract: Therapeutic administration of regulatory T cells (Tregs) leads to engraftment of conventional doses of allogeneic bone marrow (BM) in nonirradiated recipient mice conditioned with costimulation blockade and mammalian target of rapamycin inhibition. The mode of action responsible for this Treg effect is poorly understood but may encompass the control of costimulation blockade–resistant natural killer (NK) cells. We show that transient NK cell depletion at the time of BM transplantation led to BM engraftment and persistent chimerism without Treg transfer but failed to induce skin graft tolerance. In contrast, the permanent absence of anti–donor NK reactivity in mice grafted with F1 BM was associated with both chimerism and tolerance comparable to Treg therapy, implying that NK cell tolerization is a critical mechanism of Treg therapy. Indeed, NK cells of Treg-treated BM recipients reshaped their receptor repertoire in the presence of donor MHC in a manner suggesting attenuated donor reactivity. These results indicate that adoptively transferred Tregs prevent BM rejection, at least in part, by suppressing NK cells and promote tolerance by regulating the appearance of NK cells expressing activating receptors to donor class I MHC.
      PubDate: 2017-06-06T10:15:28.593978-05:
      DOI: 10.1111/ajt.14342
  • Effects of DNA Methylation on Progression to Interstitial Fibrosis and
           Tubular Atrophy in Renal Allograft Biopsies: A Multi-Omics Approach
    • Authors: S. V. Bontha; D. G. Maluf, K. J. Archer, C. I. Dumur, M. G. Dozmorov, A. L. King, E. Akalin, T. F. Mueller, L. Gallon, V. R. Mas
      Pages: 3060 - 3075
      Abstract: Progressive fibrosis of the interstitium is the dominant final pathway in renal destruction in native and transplanted kidneys. Over time, the continuum of molecular events following immunological and nonimmunological insults lead to interstitial fibrosis and tubular atrophy and culminate in kidney failure. We hypothesize that these insults trigger changes in DNA methylation (DNAm) patterns, which in turn could exacerbate injury and slow down the regeneration processes, leading to fibrosis development and graft dysfunction. Herein, we analyzed biopsy samples from kidney allografts collected 24 months posttransplantation and used an integrative multi-omics approach to understand the underlying molecular mechanisms. The role of DNAm and microRNAs on the graft gene expression was evaluated. Enrichment analyses of differentially methylated CpG sites were performed using GenomeRunner. CpGs were strongly enriched in regions that were variably methylated among tissues, implying high tissue specificity in their regulatory impact. Corresponding to this methylation pattern, gene expression data were related to immune response (activated state) and nephrogenesis (inhibited state). Preimplantation biopsies showed similar DNAm patterns to normal allograft biopsies at 2 years posttransplantation. Our findings demonstrate for the first time a relationship among epigenetic modifications and development of interstitial fibrosis, graft function, and inter-individual variation on long-term outcomes.
      PubDate: 2017-07-08T10:30:41.792505-05:
      DOI: 10.1111/ajt.14372
  • Donor–Recipient Matching Based on Predicted Indirectly Recognizable HLA
           Epitopes Independently Predicts the Incidence of De Novo Donor-Specific
           HLA Antibodies Following Renal Transplantation
    • Authors: N. Lachmann; M. Niemann, P. Reinke, K. Budde, D. Schmidt, F. Halleck, A. Pruß, C. Schönemann, E. Spierings, O. Staeck
      Pages: 3076 - 3086
      Abstract: De novo donor-specific HLA antibodies (dnDSA) are recognized as a risk factor for premature allograft failure. Determinants of DSA specificity are generated via the indirect allorecognition pathway. Here, we present supportive data for the relevance of predicted indirectly recognizable HLA epitopes (PIRCHE) to predict dnDSA following kidney transplantation. A total of 2787 consecutive kidney transplants performed between 1995 and 2015 without preformed DSA have been analyzed. De novo DSA were detected by single antigen bead assay. HLA epitope mismatches were determined by the HLAMatchmaker and PIRCHE approach and correlated in uni- and multivariate analyses with 10-year allograft survival and incidence of dnDSA. The PIRCHE-II score moderately predicted allograft survival. However, the predictive value of elevated PIRCHE-II scores>9 for the incidence of dnDSA was statistically significant (p < 0.001). In a multivariate Cox regression analysis adjusted for antigen mismatch and HLAMatchmaker epitopes, the PIRCHE-II score could be identified as an independent risk factor for dnDSA. The PIRCHE-II score independently from the antigen mismatch and HLAMatchmaker epitopes could be revealed as being a strong predictor for dnDSA. PIRCHE may help to identify acceptable mismatches with decreased risk of dnDSA and thus improve long-term renal allograft survival.
      PubDate: 2017-07-28T08:30:29.168673-05:
      DOI: 10.1111/ajt.14393
  • Ultrasound Imaging Based on Molecular Targeting for Quantitative
           Evaluation of Hepatic Ischemia–Reperfusion Injury
    • Authors: C. Qiu; T. Yin, Y. Zhang, Y. Lian, Y. You, K. Wang, R. Zheng, X. Shuai
      Pages: 3087 - 3097
      Abstract: The aim of the present study was to quantitatively diagnose and monitor the therapy response of hepatic ischemia–reperfusion injury (IRI) with the use of targeted ultrasound (US) imaging. Targeted microbubbles (MBs) were fabricated, and the binding of intracellular adhesion molecule 1 (ICAM-1) antibodies to MBs was observed. To establish a quantitative method based on targeted US imaging, contrast-enhanced US was applied for IRI rats. After andrographolide treatment, the IRI rats were subjected to the quantitative targeted US imaging for a therapeutic effect. Effective binding of ICAM-1 antibodies to MBs was observed. According to the quantitative targeted US imaging, the ICAM-1 normalized intensity difference (NID) in the IRI rats (38.74 ± 15.08%) was significantly higher than that in the control rats (10.08 ± 2.52%, p = 0.048). Further, different degrees of IRI (mild IRI, moderate to severe IRI) were distinguished by the use of the NID (37.14 ± 2.14%, 22.34 ± 1.08%, p = 0.002). Analysis of mRNA expression demonstrated the accuracy of analyzing the NID by using quantitative targeted US imaging (R2 = 0.7434, p 
      PubDate: 2017-06-08T09:43:12.56149-05:0
      DOI: 10.1111/ajt.14345
  • In Vitro Induction of Human Regulatory T Cells Using Conditions of Low
           Tryptophan Plus Kynurenines
    • Authors: K. L. Hippen; R. S. O'Connor, A. M. Lemire, A. Saha, E. A. Hanse, N. C. Tennis, S. C. Merkel, A. Kelekar, J. L. Riley, B. L. Levine, C. H. June, L. A. Turka, L. S. Kean, M. L. MacMillan, J. S. Miller, J. E. Wagner, D. H. Munn, B. R. Blazar
      Pages: 3098 - 3113
      Abstract: Thymic regulatory T cells (tTregs) and induced regulatory T cells (iTregs) suppress murine acute graft-versus-host disease (GVHD). Previously, we demonstrated that the plasmacytoid dendritic cell indoleamine 2,3-dioxygenase (IDO) fosters the in vitro development of human iTregs via tryptophan depletion and kynurenine (Kyn) metabolites. We now show that stimulation of naïve CD4+ T cells in low tryptophan (low Trp) plus Kyn supports human iTreg generation. In vitro, low Trp + Kyn iTregs and tTregs potently suppress T effector cell proliferation equivalently but are phenotypically distinct. Compared with tTregs or T effector cells, bioenergetics profiling reveals that low Trp + Kyn iTregs have increased basal glycolysis and oxidative phosphorylation and use glutaminolysis as an energy source. Low Trp + Kyn iTreg viability was reliant on interleukin (IL)-2 in vitro. Although in vivo IL-2 administration increased low Trp + Kyn iTreg persistence on adoptive transfer into immunodeficient mice given peripheral blood mononuclear cells to induce GVHD, IL-2–supported iTregs did not improve recipient survival. We conclude that low Trp + Kyn create suppressive iTregs that have high metabolic needs that will need to be addressed before clinical translation.
      PubDate: 2017-06-14T07:55:25.922552-05:
      DOI: 10.1111/ajt.14338
  • Impact of Protease Inhibitor–Based Anti-Retroviral Therapy on Outcomes
           for HIV+ Kidney Transplant Recipients
    • Authors: D. Sawinski; B. A. Shelton, S. Mehta, R. D. Reed, P. A. MacLennan, S. Gustafson, D. L. Segev, J. E. Locke
      Pages: 3114 - 3122
      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. Intercontinental Marketing Services (IMS) pharmacy fills (1/1/01–10/1/12) were linked with Scientific Registry of Transplant Recipients (SRTR) data. A total of 332 recipients with pre- and posttransplantation fills were characterized by ART at the time of transplantation 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 Survival (EPTS) score of>20% (70.9% vs. 56.3%, p = 0.02) than those on non-PI regimens. On adjusted analyses, PI-based regimens were associated with a 1.8-fold increased risk of allograft loss (adjusted hazard ratio [aHR] 1.84, 95% confidence interval [CI] 1.22–2.77, p = 0.003), with the greatest risk observed in the first posttransplantation year (aHR 4.48, 95% CI 1.75–11.48, p = 0.002), and a 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 that whenever possible, recipients should be converted to a non-PI regimen prior to kidney transplantation.
      PubDate: 2017-08-24T09:44:59.650994-05:
      DOI: 10.1111/ajt.14419
  • The Incremental Cost of Incompatible Living Donor Kidney Transplantation:
           A National Cohort Analysis
    • Authors: D. Axelrod; K. L. Lentine, M. A. Schnitzler, X. Luo, H. Xiao, B. J. Orandi, A. Massie, J. Garonzik-Wang, M. D. Stegall, S. C. Jordan, J. Oberholzer, T. B. Dunn, L. E. Ratner, S. Kapur, R. P. Pelletier, J. P. Roberts, M. L. Melcher, P. Singh, D. L. Sudan, M. P. Posner, J. M. El-Amm, R. Shapiro, M. Cooper, G. S. Lipkowitz, M. A. Rees, C. L. Marsh, B. R. Sankari, D. A. Gerber, P. W. Nelson, J. Wellen, A. Bozorgzadeh, A. Osama Gaber, R. A. Montgomery, D. L. Segev
      Pages: 3123 - 3130
      Abstract: Incompatible living donor kidney transplantation (ILDKT) has been established as an effective option for end-stage renal disease patients with willing but HLA-incompatible living donors, reducing mortality and improving quality of life. Depending on antibody titer, ILDKT can require highly resource-intensive procedures, including intravenous immunoglobulin, plasma exchange, and/or cell-depleting antibody treatment, as well as protocol biopsies and donor-specific antibody testing. This study sought to compare the cost and Medicare reimbursement, exclusive of organ acquisition payment, for ILDKT (n = 926) with varying antibody titers to matched compatible transplants (n = 2762) performed between 2002 and 2011. Data were assembled from a national cohort study of ILDKT and a unique data set linking hospital cost accounting data and Medicare claims. ILDKT was more expensive than matched compatible transplantation, ranging from 20% higher adjusted costs for positive on Luminex assay but negative flow cytometric crossmatch, 26% higher for positive flow cytometric crossmatch but negative cytotoxic crossmatch, and 39% higher for positive cytotoxic crossmatch (p 
      PubDate: 2017-07-21T08:40:31.733825-05:
      DOI: 10.1111/ajt.14392
  • The National Landscape of Living Kidney Donor Follow-Up in the United
    • Authors: M. L. Henderson; A. G. Thomas, A. Shaffer, A. B. Massie, X. Luo, C. M. Holscher, T. S. Purnell, K. L. Lentine, D. L. Segev
      Pages: 3131 - 3140
      Abstract: In 2013, the Organ Procurement and Transplantation Network (OPTN)/ United Network for Organ Sharing (UNOS) mandated that transplant centers collect data on living kidney donors (LKDs) at 6 months, 1 year, and 2 years postdonation, with policy-defined thresholds for the proportion of complete living donor follow-up (LDF) data submitted in a timely manner (60 days before or after the expected visit date). While mandated, it was unclear how centers across the country would perform in meeting thresholds, given potential donor and center-level challenges of LDF. To better understand the impact of this policy, we studied Scientific Registry of Transplant Recipients data for 31,615 LKDs between January 2010 and June 2015, comparing proportions of complete and timely LDF form submissions before and after policy implementation. We also used multilevel logistic regression to assess donor- and center-level characteristics associated with complete and timely LDF submissions. Complete and timely 2-year LDF increased from 33% prepolicy (January 2010 through January 2013) to 54% postpolicy (February 2013 through June 2015) (p 
      PubDate: 2017-06-30T08:55:23.978375-05:
      DOI: 10.1111/ajt.14356
  • Renal Consequences of Diabetes After Kidney Donation
    • Authors: H. N. Ibrahim; D. M. Berglund, S. Jackson, D. M. Vock, R. N. Foley, A. J. Matas
      Pages: 3141 - 3148
      Abstract: Whether diabetes after kidney donation is associated with an accelerated GFR decay in the remaining kidney has not been studied. We determined the incidence of diabetes in kidney donors, and compared GFR change over time in diabetic to nondiabetic donors, in addition to the effect of diabetes mellitus (DM) on the development of proteinuria, hypertension, and end-stage renal disease (ESRD). Of the 4014 donors, 309 (7.7%) developed diabetes at a median age of 56.0 years and after a median of 18 years after donation. The difference in annual estimated GFR (eGFR) change between diabetic and nondiabetic donors in the 7 years before the development of DM was −0.08 mL/min/year; p = 0.51. After DM development, the difference was −1.10 mL/min/year for diabetic donors with hypertension and proteinuria, p < 0.001; −0.19 for diabetic donors with hypertension but no proteinuria, p = 0.29; −0.75 mL/min/year for diabetic donors with proteinuria but no hypertension, p = 0.19; and −0.09 mL/min/year for diabetic donors without proteinuria or hypertension, p = 0.63. When DM was considered as a time-dependent covariate, it was associated with the development of proteinuria (hazard ratio [HR] 2.65, 95% confidence interval [CI] 1.89–3.70; p < 0.001) and hypertension (HR 2.19, 95% CI 1.74–2.75; p < 0.001). It was not, however, associated with ESRD. eGFR decline after DM development exceeds that of nondiabetic donors only in diabetic donors with concomitant proteinuria and hypertension.
      PubDate: 2017-08-14T13:22:33.695908-05:
      DOI: 10.1111/ajt.14416
  • Harnessing Scientific and Technological Advances to Improve Equity in
           Kidney Allocation Policies
    • Authors: A. R. Tambur; B. Audry, C. Antoine, C. Suberbielle, D. Glotz, C. Jacquelinet
      Pages: 3149 - 3158
      Abstract: We reported that current assignment of HLA-DQ is a barrier to organ allocation. Here we simulated the impact of incorporating HLA-DQ antigens and antibodies as A/B and αβ allelic variants, respectively, on calculated panel reactive antibody (cPRA) and probability of finding potential compatible donors (PCD). A cohort of 1224 donors and 2075 sensitized candidates was analyzed using HLA-DQαβ allelic (study) versus serologic (current practice) nomenclature. A significant (p 
      PubDate: 2017-07-17T08:25:56.164267-05:
      DOI: 10.1111/ajt.14389
  • Impact of a National Controlled Donation After Circulatory Death (DCD)
           Program on Organ Donation in the United Kingdom: A 10-Year Study
    • Authors: R. Hodgson; A. L. Young, M. A. Attia, J. P. A. Lodge
      Pages: 3172 - 3182
      Abstract: Organ transplantation is the most successful treatment for some forms of organ failure, yet a lack of organs means many die on the waiting list. In the United Kingdom, the Organ Donation Taskforce was set up to identify barriers to organ donation and in 2008 released its first report (Organ Donation Taskforce Report; ODTR). This study assesses the success since the ODTR and examines the impact of the United Kingdom's controlled donation after circulatory death (DCD) program and the controversies surrounding it. There were 12 864 intended donation after brain death (DBD) or DCD donors from April 2004 to March 2014. When the 5 years preceding the ODTR was compared to the 5 years following, intended DCD donors increased 292% (1187 to 4652), and intended DBD donors increased 11% (3327 to 3698). Organs retrieved per intended DBD donor remained static (3.30 to 3.26), whereas there was a decrease in DCD (1.54 to 0.99) due to a large rise in donors who did not proceed to donation (325 to 2464). The majority of DCD donors who proceeded did so within 30 min from time of withdrawal. Our study suggests further work on converting eligible referrals to organ donation and exploring methods of converting DCD to DBD donors.
      PubDate: 2017-06-30T09:05:34.358679-05:
      DOI: 10.1111/ajt.14374
  • Changing Metrics of Organ Procurement Organization Performance in Order to
           Increase Organ Donation Rates in the United States
    • Authors: D. Goldberg; M. J. Kallan, L. Fu, M. Ciccarone, J. Ramirez, P. Rosenberg, J. Arnold, G. Segal, K. P. Moritsugu, H. Nathan, R. Hasz, P. L. Abt
      Pages: 3183 - 3192
      Abstract: The shortage of deceased-donor organs is compounded by donation metrics that fail to account for the total pool of possible donors, leading to ambiguous donor statistics. We sought to assess potential metrics of organ procurement organizations (OPOs) utilizing data from the Nationwide Inpatient Sample (NIS) from 2009–2012 and State Inpatient Databases (SIDs) from 2008–2014. A possible donor was defined as a ventilated inpatient death ≤75 years of age, without multi-organ system failure, sepsis, or cancer, whose cause of death was consistent with organ donation. These estimates were compared to patient-level data from chart review from two large OPOs. Among 2,907,658 inpatient deaths from 2009–2012, 96,028 (3.3%) were a “possible deceased-organ donor.” The two proposed metrics of OPO performance were: (1) donation percentage (percentage of possible deceased-donors who become actual donors; range: 20.0–57.0%); and (2) organs transplanted per possible donor (range: 0.52–1.74). These metrics allow for comparisons of OPO performance and geographic-level donation rates, and identify areas in greatest need of interventions to improve donation rates. We demonstrate that administrative data can be used to identify possible deceased donors in the US and could be a data source for CMS to implement new OPO performance metrics in a standardized fashion.
      PubDate: 2017-07-20T01:01:02.854694-05:
      DOI: 10.1111/ajt.14391
  • 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
      Pages: 3199 - 3209
      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 8 days for both recipient groups, we detected already at day 5 posttransplantation 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 setups, grafts derived from Klrk1−/− recipients were characterized by significantly higher levels of interferon-γ mRNA, and both CD4+ and CD8+ T cells displayed a greater capacity for degranulation and interferon-γ 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.
      PubDate: 2017-09-09T10:41:01.857629-05:
      DOI: 10.1111/ajt.14467
  • 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
      Pages: 3219 - 3227
      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 vs cyclosporine: hazard ratio [HR] = 0.95; 95% confidence interval [CI] 0.47-1.92; P = .89; belatacept less-intensive vs cyclosporine: HR = 1.61; 95% CI 0.85-3.05; P = .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 vs cyclosporine: HR = 1.06, 95% CI 0.35-3.17, P = .92; belatacept 8-weekly vs cyclosporine: HR = 2.00, 95% CI 0.75-5.35, P = .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 cyclosporine were 67.0, 68.7, and 42.7 mL/min per 1.73 m2, respectively (P
      PubDate: 2017-09-05T08:25:52.350503-05:
      DOI: 10.1111/ajt.14452
  • Cytomegalovirus-Induced Polyarteritis Nodosa in a Liver Transplant
    • Authors: K. Abadeer; N. Aslam, C. Cortese, H. M. Wadei
      Pages: 3236 - 3240
      Abstract: Polyarteritis nodosa (PAN) is a necrotizing vasculitis that has been associated with viral infections, especially hepatitis B virus. We hereby report a case of tissue-invasive cytomegalovirus (CMV)-induced PAN in a liver transplant recipient presenting with acute kidney injury and active urinary sediment. Treatment directed against both PAN and CMV resulted in improvement in kidney function, normalization of urinary indices and resolution of the CMV infection. There was no recurrence of either PAN or CMV after a 3-year follow-up period.
      PubDate: 2017-06-30T09:10:53.158295-05:
      DOI: 10.1111/ajt.14376
  • Illicit Drug Use, Illicit Drug Use Disorders, and Drug Overdose Deaths in
           Metropolitan and Nonmetropolitan Areas—United States
    • Authors: Karin A. Mack; Christopher M. Jones, Michael F. Ballesteros
      Pages: 3241 - 3252
      Abstract: Problem/ConditionDrug overdoses are a leading cause of injury death in the United States, resulting in approximately 52,000 deaths in 2015. Understanding differences in illicit drug use, illicit drug use disorders, and overall drug overdose deaths in metropolitan and nonmetropolitan areas is important for informing public health programs, interventions, and policies.Reporting PeriodIllicit drug use and drug use disorders during 2003–2014, and drug overdose deaths during 1999–2015.Description of DataThe National Survey of Drug Use and Health (NSDUH) collects information through face-to-face household interviews about the use of illicit drugs, alcohol, and tobacco among the U.S. noninstitutionalized civilian population aged ≥12 years. Respondents include residents of households and noninstitutional group quarters (e.g., shelters, rooming houses, dormitories, migratory workers’ camps, and halfway houses) and civilians living on military bases. NSDUH variables include sex, age, race/ethnicity, residence (metropolitan/nonmetropolitan), annual household income, self-reported drug use, and drug use disorders.National Vital Statistics System Mortality (NVSS-M) data for U.S. residents include information from death certificates filed in the 50 states and the District of Columbia. Cases were selected with an underlying cause of death based on the ICD-10 codes for drug overdoses (X40–X44, X60–X64, X85, and Y10–Y14). NVSS-M variables include decedent characteristics (sex, age, and race/ethnicity) and information on intent (unintentional, suicide, homicide, or undetermined), location of death (medical facility, in a home, or other [including nursing homes, hospices, unknown, and other locations]) and county of residence (metropolitan/nonmetropolitan).Metropolitan/nonmetropolitan status is assigned independently in each data system. NSDUH uses a three-category system: Core Based Statistical Area (CBSA) of ≥1 million persons; CBSA of
      PubDate: 2017-11-16T12:55:39.640458-05:
      DOI: 10.1111/ajt.14555
  • Acute liver failure in a pregnant patient
    • Authors: Denise J. Lo; Rachel J. Friedman-Moraco, Benjamin H. Hinrichs, Andrew B. Adams
      Pages: 3254 - 3256
      PubDate: 2017-11-16T12:55:42.822694-05:
      DOI: 10.1111/ajt.14512
  • It Is Bad Policy and Contrary to Federal Law to Prioritize Local
           Allocation of Livers to Address Geographically Based Social Inequities
    • Authors: A. K. Glazier
      Pages: 3257 - 3257
      PubDate: 2017-06-27T11:00:20.629204-05:
      DOI: 10.1111/ajt.14384
  • Equitable Access Is Not a Secondary Goal of Organ Allocation
    • Authors: K. Ladin; D. W. Hanto
      Pages: 3258 - 3258
      PubDate: 2017-07-04T17:45:38.190079-05:
      DOI: 10.1111/ajt.14387
  • Evaluation of Strategies for Increasing Transplantation Should Be Based on
           a Current and Precise Assessment of the State of Organ Donation
    • Authors: K. J. O'Connor; A. K. Glazier
      Pages: 3259 - 3259
      PubDate: 2017-07-24T14:20:28.707422-05:
      DOI: 10.1111/ajt.14398
  • ESRD in Living Donors Before 1987: Obtaining Waitlist Priority
    • Authors: R. Hays; C. Lillesand, D. A. Mandelbrot
      Pages: 3260 - 3261
      PubDate: 2017-06-19T08:40:20.132155-05:
      DOI: 10.1111/ajt.14369
  • Flawed Assumptions: Ethical Problems With Proposed Presumed Consent
    • Authors: C. R. Bruce; P. Koch
      Pages: 3262 - 3263
      PubDate: 2017-07-20T11:30:21.727667-05:
      DOI: 10.1111/ajt.14402
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