American Journal of Transplantation | Page 2

T Darius, M Vergauwen, T Smith, I Gerin, V Joris, M Mueller, S Aydin, X Muller, A Schlegel, J Nath, C Ludwig, C Dessy, M C Many, G Bommer, P Dutkowski, P Gianello, M Mourad
With oxygenation proposed as a resuscitative measure during hypothermic models of preservation, the aim of this study was to evaluate the optimal start time of oxygenation during continuous hypothermic machine perfusion (HMP). In this porcine ischemia-reperfusion autotransplant model, the left kidney of a ±40 kg pig was exposed to 30 minutes of warm ischemia prior to 22 hours of HMP and autotransplantation. Kidneys were randomized to receive 2 hours of oxygenation during HMP either at the start (n=6), or end of the perfusion (n=5) and outcomes were compared to standard, non-oxygenated HMP (n=6) and continuous oxygenated HMP (n=8)...
February 3, 2020: American Journal of Transplantation
Andrew Healey, Yui Watanabe, Caitlin Mills, Michele Stoncius, Susan Lavery, Karen Johnson, Robert Sanderson, Atul Humar, Jonathan Yeung, Laura Donahoe, Andrew Pierre, Marc de Perrot, Kazuhiro Yasufuku, Thomas K Waddell, Shaf Keshavjee, Marcelo Cypel
Uncontrolled donation after cardiac death (uDCD) has the potential to ameliorate the shortage of suitable lungs for transplantation. To date, no lung transplantation data from these donors is available from North America. Herein we describe the successful use of these donors using a simple method of in situ lung inflation so that the organ can be protected from warm ischemic injury. Forty-four potential donors were approached, and family consent was obtained in 30 cases (68%). Of these, the lung transplant team evaluated 16 uDCDs on site, and 14 were considered for transplantation pending ex vivo lung perfusion (EVLP) assessment...
January 29, 2020: American Journal of Transplantation
Garrett R Roll, Andrew M Posselt, Jonathan Freise, Julia Baird, Shareef Syed, Sang Mo Kang, Ryutaro Hirose, Gregory L Szot, Arya Zarinsefat, Sandy Feng, Giulia Worner, Minnie Sarwal, Peter G Stock
The approach to transplantation in human immunodeficiency virus (HIV)-positive patients has been conservative due to fear of exacerbating an immunocompromised condition. As a result, HIV-positive patients with diabetes were initially excluded from beta cell replacement therapy. Early reports of pancreas transplant in patients with HIV described high rates of early graft loss with limited follow up. We report long-term follow up of islet or pancreas transplantation in HIV-positive Type I diabetic patients who received a kidney transplant concurrently, or had previously undergone kidney transplantation...
January 28, 2020: American Journal of Transplantation
Mario Fernández-Ruiz, Isabel Rodríguez-Goncer, Patricia Parra, Tamara Ruiz-Merlo, Laura Corbella, Francisco López-Medrano, Natalia Polanco, Esther González, Rafael San Juan, María Dolores Folgueira, Amado Andrés, José María Aguado
Monitoring for cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) may be useful for individualizing valganciclovir (VGCV) prophylaxis after kidney transplantation (KT). We performed a commercial ELISA-based interferon (IFN)-γ release assay (QTF-CMV) from post-transplant months 2 to 5 (362 points) in 120 CMV-seropositive KT recipients that received antithymocyte globulin as induction therapy and VGCV prophylaxis (median of 92 days). Forty-seven patients (39.3%) had CMV infection after discontinuation of prophylaxis...
January 28, 2020: American Journal of Transplantation
Koichiro Minami, Soochan Bae, Hirofumi Uehara, Chen Zhao, Dongwon Lee, Jasper Iske, Michael W Fanger, Jake Reder, Ian Morrison, Haruhito Azuma, Astrid Wiens, Edward Van Keuren, Brandy Houser, Abdala El-Khal, Peter M Kang, Stefan G Tullius
Inflammatory responses associated with ischemia/reperfusion injury (IRI) play a central role in alloimmunity and transplant outcomes. A key event driving these inflammatory responses is the burst of reactive oxygen species, with hydrogen peroxide (H2 O2 ) as the most abundant form that occurs as a result of surgical implantation of the donor organ. Here, we used a syngeneic rat renal transplant and IRI model to evaluate the therapeutic properties of APP-103, a copolyoxalate molecule containing vanillyl alcohol (VA) that exhibits high sensitivity and specificity towards the production of H2 O2 ...
January 28, 2020: American Journal of Transplantation
Arno Vanstapel, Adriana Dubbeldam, Birgit Weynand, Eric K Verbeken, Robin Vos, Arne P Neyrinck, Dragoş M Vasilescu, Laurens J Ceulemans, Anna E Frick, Dirk E Van Raemdonck, Johny Verschakelen, Bart M Vanaudenaerde, Geert M Verleden, Stijn E Verleden
Donor organ shortage results in significant waiting list mortality. Donor lung assessment is currently based on donors' history, gas exchange, chest X-ray, bronchoscopy findings and ultimately in situ inspection; but remains subjective. We correlated histopathology and radiology in non-transplanted donor lungs with the clinical indications to decline the offered organ. Sixty-two donor lungs, not used for transplantation (2010-2019), were procured, air-inflated, frozen, scanned with computed tomography, systematically sampled and histologically and radiologically assessed...
January 27, 2020: American Journal of Transplantation
Ghaneh Fananapazir, Gary Tse, Ryan Di Geronimo, John McVicar, Richard Perez, Chandrasekar Santhanakrishnan, Junichiro Sageshima, Christoph Troppmann
Pediatric en bloc kidney transplants (EBKs) from small deceased pediatric donors are associated with increased early graft loss and morbidity. Yet, urologic complications post-EBK and their potential impact on graft survival have not been systematically studied. We retrospectively studied urological complications requiring intervention for 225 EBKs performed at our center 01/2005-09/2017 from donors ≤20 kg into recipients ≥18 years. Overall ureteral complication incidence after EBK was 9.8% (n=22) (12% vs...
January 26, 2020: American Journal of Transplantation
Rachel E Patzer, Laura McPherson, Zhensheng Wang, Laura C Plantinga, Sudeshna Paul, Matt Ellis, Derek A DuBay, Joshua Wolf, Amber Reeves-Daniel, Heather Jones, Carlos Zayas, Laura Mulloy, Stephen O Pastan
Variability in transplant access exists, but barriers to referral and evaluation are underexplored due to lack of national surveillance data. We examined referral for kidney transplantation evaluation and start of the evaluation among 34,857 incident, adult (18-79 years) end-stage kidney disease patients from 690 dialysis facilities in the United States Renal Data System from 1/2012 through 8/31/2016, followed through 2/2018 and linked data to referral and evaluation data from nine transplant centers in Georgia, North Carolina, and South Carolina...
January 25, 2020: American Journal of Transplantation
Jeremy S Nayagam, Samuel McGrath, Mahmoud Montasser, Michael Delaney, Tom D Cairns, Kevin J Marchbank, Harriet Denton, Yi Yang, Steven H Sacks, H Terry Cook, Sapna Shah, Nigel Heaton, Matthew C Pickering, Abid Suddle
Hereditary complement C3 deficiency is associated with recurrent bacterial infections and proliferative glomerulonephritis. We describe a case of an adult with complete deficiency of complement C3 due to homozygous mutations in C3 gene: c.1811delT (Val604Glyfs*2), recurrent bacterial infections, crescentic glomerulonephritis, and end-stage renal failure. Following isolated kidney transplantation he would remain C3 deficient with a similar, or increased, risk of infections and glomerulonephritis. As C3 is predominantly synthesized in the liver, with a small proportion of C3 monocyte derived and kidney derived, he proceeded to simultaneous liver-kidney transplantation...
January 23, 2020: American Journal of Transplantation
Reem Daloul, Todd Pesavento, Anthony Michaels
Since the publication of the first two novel reports demonstrating the feasibility of using Hepatitis C virus nucleic acid test positive (HCV NAT+) organs into negative recipients1,2 , evidence regarding the safety of using HCV NAT+ organs have been mounting. However, the wide implementation of such a practice hinges on the ability to ensure timely delivery of direct acting antiviral (DAA) therapy after transplantation. To date, DAA coverage by third party payers for acute HCV infection cannot be guaranteed...
January 22, 2020: American Journal of Transplantation
Ji Won Han, Dong Jin Joo, Jong Hoon Kim, Min-Seok Rha, June Young Koh, Hye Jung Park, Jae Geun Lee, Myoung Soo Kim, Soon Il Kim, Eui-Cheol Shin, Jun Yong Park, Su-Hyung Park
Treg cells are important in preventing acute rejection (AR) in solid organ transplantation, but the clinical relevance of the different kinetics early after liver transplantation (LT) in acute rejectors and non-rejectors is unclear. We analyzed peripheral blood samples of 128 LT recipients receiving basiliximab induction plus tacrolimus immunosuppression. Samples were obtained at pre-transplantation, D7, and D30 after LT. Frequency and phenotype of Tregs were analyzed by flow cytometry. The predictive value of Treg frequency at D7 was assessed for suspected acute rejection (SAR) and was validated for biopsy-proven AR (BPAR)...
January 22, 2020: American Journal of Transplantation
Tayyab S Diwan, Tiffany C Lee, Shunji Nagai, Enrico Benedetti, Andrew Posselt, Ginny Bumgardner, Sabrena Noria, Bryan A Whitson, Lloyd Ratner, David Mason, Jon Friedman, Kenneth J Woodside, Julie Heimbach
The increasing obesity epidemic has major implications in the realm of transplantation. Patients with obesity face barriers in access to transplantation as well as unique challenges in perioperative and postoperative outcomes. Due to comorbidities associated with obesity along with the underlying end-stage organ disease leading to transplantation candidacy, these patients may not even be referred for transplant evaluation, much less be waitlisted or actually undergo transplantation. However, the utilization of bariatric surgery in this population can help optimize the transplant candidacy of patients with obesity and end-stage organ disease as well as improve perioperative and postoperative outcomes...
January 21, 2020: American Journal of Transplantation
Sharad I Wadhwani, Andrew F Beck, John Bucuvalas, Laura Gottlieb, Uma Kotagal, Jennifer C Lai
Long-term outcomes remain suboptimal following pediatric liver transplantation; only one-third of children have normal biochemical liver function without immunosuppressant comorbidities 10 years post-transplant. We examined the association between an index of neighborhood socioeconomic deprivation with graft and patient survival using the Scientific Registry of Transplant Recipients. We included children <19 years who underwent liver transplantation between 1/1/2008-12/31/2013 (n=2868). Primary exposure was a neighborhood socioeconomic deprivation index-linked via patient home ZIP code-with a range of 0-1 (values nearing 1 indicate neighborhoods with greater socioeconomic deprivation)...
January 20, 2020: American Journal of Transplantation
Antoine Sicard, Caroline Lamarche, Madeleine Speck, May Wong, Isaac Rosado-Sánchez, Mathilde Blois, Nicolas Glaichenhaus, Majid Mojibian, Megan K Levings
Cell therapy with autologous donor-specific regulatory T cells (Tregs) is a promising strategy to minimize immunosuppression in transplant recipients. Chimeric antigen receptor (CAR) technology has recently been used successfully to generate donor-specific Tregs and overcome the limitations of enrichment protocols based on repetitive stimulations with alloantigens. However, the ability of CAR-Treg therapy to control alloreactivity in immunocompetent recipients is unknown. We first analyzed the effect of donor-specific CAR Tregs on alloreactivity in naive, immunocompetent mice receiving skin allografts...
January 19, 2020: American Journal of Transplantation
Elizabeth L Godfrey, Tahir H Malik, Jennifer C Lai, Ayse L Mindikoglu, N Thao N Galván, Ronald T Cotton, Christine A O'Mahony, John A Goss, Abbas Rana
We appreciate Kwong et al.'s utilization of Harrell's c-statistic and its ability to incorporate follow-up time as a valuable contribution to the discussion about our group's findings.1 We acknowledge that the conventional area under receiver-operating-characteristic curve concordance statistic has limitations; however, we selected the conventional c-statistic to remain methodologically consistent with the manner in which the Model for End-Stage Liver Disease (MELD) was originally designed and validated, first to predict post-TIPS survival, then when applied to ESLD generally, and finally when integrated into allocation...
January 14, 2020: American Journal of Transplantation
Alex Manara, Sam D Shemie, Stephen Large, Andrew Healey, Andrew Baker, Mitesh Badiwala, Marius Berman, Andrew J Butler, Prosanto Chaudhury, John Dark, John Forsythe, Darren H Freed, Dale Gardiner, Dan Harvey, Laura Hornby, Janet MacLean, Simon Messer, Gabriel C Oniscu, Christy Simpson, Jeanne Teitelbaum, Sylvia Torrance, Lindsay C Wilson, Christopher J E Watson
There is international variability in the determination of death. Death in donation after circulatory death (DCD) can be defined by the permanent cessation of brain circulation. Post-mortem interventions that restore brain perfusion should be prohibited as they invalidate the diagnosis of death. Retrieval teams should develop protocols that ensure the continued absence of brain perfusion during DCD organ recovery. In situ normothermic regional perfusion (NRP) or restarting the heart in the donor's body may interrupt the permanent cessation of brain perfusion since, theoretically, collateral circulations may restore it...
January 10, 2020: American Journal of Transplantation
Jennifer Verbesey, Alvin G Thomas, Matt Ronin, Jennifer Beaumont, Amy Waterman, Dorry L Segev, Stuart M Flechner, Matthew Cooper
Cooperative kidney paired donation (KPD) networks account for an increasing proportion of all living donor kidney transplants in the United States. There is sparse data on the rate of primary non-function (PNF) losses and their consequences within KPD networks. We studied National Kidney Registry (NKR) transplants (2/14/2009-12/31/2017) and quantified PNF, graft loss within 30 days of transplantation, and graft losses in the first year post-transplant and assessed potential risk factors. Of 2364 transplants, there were 38 (1...
January 10, 2020: American Journal of Transplantation
Juan S Danobeitia, Tiffany J Zens, Peter J Chlebeck, Laura J Zitur, Jose A Reyes, Michael J Eerhart, Jennifer Coonen, Saverio Capuano, Anthony M D'Alessandro, Jose R Torrealba, Daniel Burguete, Kevin Brunner, Edwin Van, Amersfoort, Yolanda Ponstein-Simarro Doorten, Cees Van Kooten, Ewa Jankowska-Gan, William Burlingham, Jeremy Sullivan, Arjang Djamali, Myron Pozniak, Yucel Yankol, Luis A Fernandez
Delayed graft function (DGF) in renal transplantation is associated with reduced graft survival and increased immunogenicity. The complement-driven inflammatory response after brain death (BD) and post-transplant reperfusion injury play significant roles in the pathogenesis of DGF. In a non-human primate model, we tested complement-blockade in BD donors to prevent DGF and improve graft survival. BD donors were maintained 20-hours, kidneys were procured and stored at 4°C for a 43-48 hours prior to implantation into ABO-compatible, non-sensitized, MHC-mismatched recipients...
January 10, 2020: American Journal of Transplantation
Ankit Bharat
Lung transplantation, while increasingly being offered to an expanding list of end-stage lung diseases, still suffers from poor long-term outcomes due to the development of allograft rejection. Regulatory Foxp3+ T cells have emerged as important modulators of lung transplant tolerance (1). Bronchus-associated lymphoid tissue (BALT), enriched in Foxp3+ T cells as well as B cells, develops following lung transplantation. While some studies have implicated BALT in the pro-inflammatory host response and allograft rejection, others have shown that BALT promotes tolerance, predominantly through the accumulation of Foxp3+ T cells (2, 3)...
January 9, 2020: American Journal of Transplantation
Kiran Bambha, Alexandra Shingina, Jennifer L Dodge, Kevin O'Connor, Sue Dunn, Jennifer Prinz, Mark Pabst, Kathy Nilles, Lena Sibulesky, Scott W Biggins
U.S. deceased donor solid organ transplantation (dd-SOT) depends upon an individual's/family's altruistic willingness to donate organs after death; however, there is a shortage of deceased organ donors in the U.S. Informing individuals of their own lifetime risk of needing dd-SOT could reframe the decision-making around organ donation after death. Using United Network for Organ Sharing (UNOS) data (2007-2016), this cross-sectional study identified: (i)deceased organ donors; (ii)individuals wait-listed for dd-SOT (liver, kidney, pancreas, heart, lung, intestine); (iii)dd-SOT recipients...
January 9, 2020: American Journal of Transplantation
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