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American Journal of Transplantation

Paige M Porrett, Peter P Reese, Vera Holzmayer, Kelly E Coller, Mary Kuhns, Vivianna M Van Deerlin, Caren Gentile, Jennifer R Smith, Anna Sicilia, Ashley Woodards, Rhondalyn McLean, Peter Abt, Roy D Bloom, K Rajender Reddy, Emily Blumberg, Gavin Cloherty, David Goldberg
HCV seroconversion among HCV-uninfected transplant recipients from HCV-infected (NAT+/Antibody+) or HCV-exposed (NAT-/Antibody+) donors has been reported. However, the origin of anti-HCV antibody and the implications of seroconversion remain unknown. We longitudinally tested plasma from HCV-uninfected kidney (n=31) or heart transplant recipients (n=9) of an HCV NAT+ organ for anti-HCV antibody (both IgG and IgM isotypes). Almost half of all participants had detectable anti-HCV antibody at any point during follow-up...
May 7, 2019: American Journal of Transplantation
Michael Oellerich, Maria Shipkova, Thomas Asendorf, Philip D Walson, Verena Schauerte, Nina Mettenmeyer, Mariana Kabakchiev, Georg Hasche, Hermann-Josef Gröne, Tim Friede, Eberhard Wieland, Vedat Schwenger, Ekkehard Schütz, Julia Beck
Donor-derived cell-free DNA (dd-cfDNA) is a non-invasive biomarker for comprehensive monitoring of allograft injury and rejection in kidney transplantation (KTx). dd-cfDNA quantification of copies/mL plasma [dd-cfDNA(cp/mL)] was compared to dd-cfDNA fraction [dd-cfDNA(%)] at pre-specified visits in 189 patients over one year post KTx. In patients (N=15, n=22 samples) with biopsy-proven rejection (BPR), median dd-cfDNA(cp/mL) was 3.3-fold and median dd-cfDNA(%) 2.0-fold higher (82cp/mL; 0.57% respectively) than medians in Stable Phase patients (N=83, n=408) without rejection (25cp/mL; 0...
May 7, 2019: American Journal of Transplantation
Alexandra Dili, Claude Bertrand, Valérie Lebrun, Boris Pirlot, Isabelle A Leclercq
Portal hyperperfusion and "dearterialization" of the liver remnant are the main pathogenic mechanisms for Small For Size syndrome (SFSS). ALPPS induces rapid remnant hypertrophy. We hypothesized similar increase in portal pressure/flow into the future liver remnant in ALPPS and SFSS-setting hepatectomies. In a rodent model, ALPPS was compared to SFSS-setting hepatectomy. We assessed mortality, remnant hypertrophy, hepatocyte proliferation, portal and hepatic artery flow, hypoxia-induced response and liver sinusoidal morphology...
May 7, 2019: American Journal of Transplantation
Kyle R Jackson, Sheng Zhou, Jessica Ruck, Allan B Massie, Courtenay Holscher, Amber Kernodle, Jaime Glorioso, Jennifer Motter, Alicia Neu, Niraj Desai, Dorry L Segev, Jacqueline Garonzik-Wang
The Kidney Allocation System (KAS) has resulted in fewer pediatric kidneys being allocated to pediatric deceased donor kidney transplant (pDDKT) recipients. This had prompted concerns that post-pDDKT outcomes may worsen. To study this, we used SRTR data to compare outcomes of 953 pre-KAS pDDKT (age<18 years) recipients (12/4/2012-12/3/2014) to 934 post-KAS pDDKT recipients (12/4/2014-12/3/2016). We analyzed mortality and graft loss using Cox regression, delayed graft function (DGF) using logistic regression, and length of stay (LoS) using negative binomial regression...
May 7, 2019: American Journal of Transplantation
Aleksandar Senev, Evelyne Lerut, Vicky Van Sandt, Maarten Coemans, Jasper Callemeyn, Ben Sprangers, Dirk Kuypers, Marie-Paule Emonds, Maarten Naesens
In this cohort study (N=924), we investigated the evolution and clinical significance of pretransplant donor-specific HLA antibodies (preDSA), detected in the single-antigen beads assay but CDC-crossmatch-negative. Donor specificity of the preDSA (N=107) was determined by high-resolution genotyping of donor-recipient pairs. We found that in 52% of the patients with preDSA, preDSA spontaneously resolved within the first 3 months posttransplant. PreDSA that persisted posttransplant had higher pretransplant MFI values and more specificity against DQ...
May 6, 2019: American Journal of Transplantation
Johanna Egelkamp, Evgeny Chichelnitskiy, Jenny F Kühne, Franziska Wandrer, Kerstin Daemen, Jana Keil, Jan Hinrich Bräsen, Jessica Schmitz, Ramon Bellmàs-Sanz, Susanne Iordanidis, Katherina Katsirntaki, Kevin Hake, Ali Akhdar, Christine Neudörfl, Hermann Haller, Cornelia Blume, Christine S Falk
The role of endothelial cells in the pathophysiology of antibody-mediated rejection after renal transplantation has been widely investigated. We expand this scenario to the impact of epithelial cells on the microenvironment during rejection. Primary proximal tubular epithelial cells were stimulated via HLA class I, CD155 and CD166 based on their potential signal-transducing capacity to mediate back signaling after encounter with either T/NK cells or donor-specific antibodies. Upon crosslinking of these ligands with mAbs, PTEC secreted IL-6, CXCL1,8,10, CCL2 and sICAM-1...
May 6, 2019: American Journal of Transplantation
Simon Moosburner, Igor M Sauer, Joseph M G V Gassner, Christina Schleicher, Detlef Bösebeck, Axel Rahmel, Johann Pratschke, Nathanael Raschzok
We read, with great interest, the work from Croome et al. on "The impact of post-reperfusion syndrome using livers with significant macrosteatosis" in which the authors demonstrate in a propensity score matched cohort, that steatosis hepatis is associated with post-reperfusion syndrome (PRS), early allograft dysfunction (EAD) and renal dysfunction, while not directly affecting graft or patient survival. This article is protected by copyright. All rights reserved.
May 6, 2019: American Journal of Transplantation
Rebecca R Lehman, Kevin M Chan
Following the issuance of the Final Rule governing the Organ Procurement and Transplantation Network (OPTN) in 1998, the then Chair of the OPTN Thoracic Transplantation Committee (hereafter referred to as the Committee) cited and supported the American Society of Transplant Surgeons (ASTS) testimony before congress stating "giving priority to the sickest patients first over broad geographic areas would be wasteful and dangerous, resulting in fewer patients transplanted, increased death rates, increased re-transplantation due to poor organ function and increased overall cost of transplantation(1)"...
April 30, 2019: American Journal of Transplantation
Caitlin M Forker, Todd A Miano, John P Reilly, Michelle L Oyster, Mary K Porteous, Edward E Cantu, Lorraine B Ware, Joshua M Diamond, Jason D Christie, Michael G S Shashaty
Acute kidney injury (AKI) is common after lung transplantation, but molecular markers remain poorly studied. The endothelial activation markers soluble thrombomodulin (sTM), protein C, and plasminogen activator inhibitor-1 (PAI-1) are implicated in kidney microcirculatory injury in animal models of AKI. We tested the association of 6-hour post-reperfusion plasma levels of these markers with post-transplant AKI severity in patients enrolled in the Lung Transplant Outcomes Group prospective cohort study at the University of Pennsylvania during two eras: 2004-06 (n=61) and 2013-15 (n=67)...
April 24, 2019: American Journal of Transplantation
Sehoon Park, Heounjeong Go, Chung Hee Baek, Young Hoon Kim, Yong Chul Kim, Seung Hee Yang, Jung Pyo Lee, Sang-Il Min, Jongwon Ha, Eun Young Song, Yon Su Kim, Su-Kil Park, Hajeong Lee, Kyung Chul Moon
With the recent update to the Oxford classification for allograft IgA nephropathy (IgAN), additional investigations on the clinical significance of the updated components are warranted. We performed a retrospective cohort study at two tertiary hospitals. Kidney transplant recipients diagnosed with allograft IgAN were included in the study after additional review by specialized pathologists. We applied the updated Oxford classification and determined the MEST-C scores of the patients. The main study outcome was death-censored graft failure within 10 years after the establishment of allograft IgAN diagnosis and was assessed using Cox regression analysis...
April 24, 2019: American Journal of Transplantation
Tatyana Kushner, Danielle Tholey, Jennifer Dodge, Behnam Saberi, Thomas Schiano, Norah Terrault
Acute fatty liver of pregnancy (AFLP) often resolves after pregnancy delivery but can progress to acute liver failure necessitating liver transplantation. We performed a retrospective review of the national Scientific Registry of Transplant Recipients (SRTR) data to identify all women in the United States undergoing liver transplantation (LT) for acute liver failure (ALF) from AFLP from 1991 to 2015, and compared to outcomes in women of childbearing age undergoing transplant for ALF from acetaminophen and ALF from other etiologies...
April 24, 2019: American Journal of Transplantation
Denis Glotz, Graeme Russ, Lionel Rostaing, Christophe Legendre, Gunnar Tufveson, Steve Chadban, Josep Grinyó, Nizam Mamode, Paolo Rigotti, Lionel Couzi, Matthias Büchler, Silvio Sandrini, Bradley Dain, Mary Garfield, Masayo Ogawa, Tristan Richard, William H Marks
The presence of preformed donor-specific antibodies (DSAs) in transplant recipients increases risk of acute antibody-mediated rejection (AMR). Results of an open-label, single-arm trial to evaluate safety and efficacy of eculizumab in preventing acute AMR in recipients of deceased-donor kidney transplants with preformed DSAs are reported. Participants received eculizumab as follows: 1200 mg immediately before reperfusion, 900 mg on posttransplantation days 1, 7, 14, 21 and 28, and 1200 mg at weeks 5, 7 and 9...
April 23, 2019: American Journal of Transplantation
Ivan Linares-Cervantes, Juan Echeverri, Stuart Cleland, Moritz Kaths, Roizar Rosales, Toru Goto, Dagmar Kollmann, Matyas Hamar, Peter Urbanellis, Laura Mazilescu, Sujani Ganesh, Oyedele A Adeyi, Paul Yip, Paulina Goryńska, Barbara Bojko, Krzysztof Goryński, David R Grant, Nazia Selzner, Marcin Wąsowicz, Markus Selzner
Normothermic ex-situ liver perfusion(NEsLP) offers the opportunity to assess biomarkers of graft function and injury. We investigated NEsLP parameters(biomarkers and markers) for the assessment of liver viability in a porcine transplantation model. Grafts from heart beating donors(HBD), and from donors with 30'(DCD30'), 70'(DCD70') and 120'(DCD120') of warm ischemia were studied. The HBD, DCD30' and DCD70'-groups had 100% survival. In contrast, 70% developed primary non-function(PNF) and died in the DCD120'-group...
April 23, 2019: American Journal of Transplantation
David M Rosenfeld, Maxwell L Smith, David P Seamans, Emmanouil Georgakis, Brantley D Gaitan, Narjeet Khurmi, Bashar A Aqel, Kunam S Reddy
Organ shortage is a major cause of delayed liver transplantation and increased wait list time. The level of donor steatosis is a significant determinant in organ selection. Scarcity of organs has led some programs to expand their acceptable criteria for the percentage of steatosis. We report two cases of liver transplantation of steatotic donor organs that resulted in mortality within hours from transplant. Postmortem analysis showed evidence of diffuse pulmonary fat microemboli likely originating from the donor organ with marked preservation reperfusion injury...
April 23, 2019: American Journal of Transplantation
Michal A Mankowski, Martin Kosztowski, Subramanian Raghavan, Jacqueline M Garonzik-Wang, David Axelrod, Dorry L Segev, Sommer E Gentry
Placing non-ideal kidneys quickly might reduce discard. We studied changing kidney allocation to eliminate sequential offers, instead making offers to multiple centers for all non-locally allocated kidneys, so that multiple centers must accept or decline within the same one hour. If more than one center accepted an offer, the kidney would go to the highest-priority accepting candidate. Using 2010 KPSAM-SRTR data, we simulated the allocation of 12,933 kidneys, excluding locally allocated and zero-mismatch kidneys...
April 23, 2019: American Journal of Transplantation
Anil Chandraker, Kenneth A Andreoni, Robert S Gaston, John Gill, Jayme E Locke, Amit K Mathur, Douglas J Norman, Rachel E Patzer, Abbas Rana, Lloyd E Ratner, Jesse D Schold, Timothy L Pruett
In accordance with the National Organ Transplant Act and HHS's Final Rule, the Scientific Registry of Transplant Recipients (SRTR) publicly releases biannual program-specific reports which include analyses of transplant centers' risk-adjusted wait-list mortality, organ acceptance ratios, transplant rates, and graft and patient survival. Since the inception of these center metrics, one-year post-transplant graft and patient survival have improved, and center variation has decreased, casting uncertainty on their clinical relevance...
April 23, 2019: American Journal of Transplantation
Abbie D Leino, Chie Emoto, Tsuyoshi Fukuda, Michael Privitera, Alexander A Vinks, Rita R Alloway
Cannabidiol (CBD), a major purified non-psychoactive component of cannabis with anticonvulsant properties, was approved by the Food and Drug Administration in June 2018 as an adjuvant treatment for refractory epilepsy (Epidiolex; GW Pharmaceuticals). CBD is metabolized by CYP3A4 and CYP2C19 with a growing body of evidence suggesting it is also a potent inhibitor of these pathways. We report for the first time a significant drug-drug interaction between the purified CBD product and tacrolimus. A participant in a CBD clinical trial for epilepsy who was also receiving tacrolimus showed an approximately 3-fold increase in dose normalized tacrolimus concentrations while receiving 2000-2900 mg/day of CBD...
April 23, 2019: American Journal of Transplantation
Jennifer C Lai, Christopher J Sonnenday, Elliot B Tapper, Andres Duarte-Rojo, Michael A Dunn, William Bernal, Elizabeth J Carey, Srinivasan Dasarathy, Binita Kamath, Matthew R Kappus, Aldo J Montano-Loza, Shunji Nagai, Puneeta Tandon
Frailty has emerged as a powerful predictor of outcomes in patients with cirrhosis and has inevitably made its way into decision-making within liver transplantation. In an effort to harmonize integration of the concept of frailty among transplant centers, the AST and ASTS supported the efforts of our working group to develop this statement from experts in the field. Frailty is a multi-dimensional construct that represents the end-manifestation of derangements of multiple physiologic systems leading to decreased physiologic reserve and increased vulnerability to health stressors...
April 13, 2019: American Journal of Transplantation
Jefferson M Jones, Brian M Gurbaxani, Alice Asher, Stephanie Sansom, Pallavi Annambhotla, Anne C Moorman, John T Brooks, Sridhar V Basavaraju
To reduce the risk of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) transmission through organ transplantation, donors are universally screened for these infections by nucleic acid tests (NAT). Deceased organ donors are classified as "increased risk" if they engaged in specific behaviors during the 12 months before death. We developed a model to estimate the risk of undetected infection for HIV, HBV, and HCV among NAT-negative donors specific to the type and timing of donors' potential risk behavior to guide revisions to the 12-month timeline...
April 13, 2019: American Journal of Transplantation
Justin R Parekh, Ryutaro Hirose, David Foley, Arielle Grieco, Mark E Cohen, Bruce L Hall, Clifford Y Ko, Stuart Greenstein
The National Surgical Quality Program (NSQIP) Transplant program was designed by transplant surgeons from the ground up to track post-transplant outcomes beyond basic recipient and graft survival. After an initial pilot phase, the program has expanded to 29 participating sites and enrolled more than 4300 recipient-donor pairs into the database, including 2876 complete kidney transplant cases. In this analysis, surgical site infection (SSI), urinary tract infection (UTI) and re-operation/intervention were evaluated for kidney transplant recipients...
April 12, 2019: American Journal of Transplantation
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