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American Journal of Transplantation

Andrew J Cowan, Christopher K Johnson, Edward N Libby
Plasma cell diseases are a class of hematologic diseases that are sometimes present as pre-existing diagnoses prior to organ transplantation, causative factors leading to a need for organ transplantation, or may occur post-transplant as part of the spectrum of post-transplant lymphoproliferative disorders. Herein, we review the most common plasma cell diseases, both as co-existing with other causes of organ failure, but also as a primary underlying cause for organ failure. In many cases, treatment of the underlying clonal disease may be indicated before proceeding with organ transplant...
March 9, 2018: American Journal of Transplantation
Christopher R Ensor, Carlo J Iasella, Kate M Harrigan, Matthew R Morrell, Cody A Moore, Norihisa Shigemura, Adriana Zeevi, John F McDyer, Raman Venkataramanan
Calcineurin inhibitors (CNIs) are the backbone of traditional immunosuppressive regimens for lung transplant recipients (LTR). The CNIs are both narrow therapeutic index drugs with significant interpatient and intrapatient variability that require therapeutic drug monitoring to ensure safety and effectiveness. We hypothesized that tacrolimus time-in-therapeutic range (TTR) affects acute and chronic rejection rates in LTRs. This was a single-center, observational, cross-sectional study of 292 adult LTRs. Subjects who received tacrolimus post-transplant for the first year were included...
March 7, 2018: American Journal of Transplantation
Jay A Fishman
Hurdles exist to clinical xenotransplantation including potential infectious transmission from non-human species to xenograft recipients. In anticipation of clinical trials of xenotransplantation, the associated infectious risks have been investigated. Swine and immunocompromised humans share some potential pathogens. Swine herpesviruses including porcine cytomegalovirus (PCMV) and porcine lymphotropic herpesvirus (PLHV) are largely species-specific and do not, generally, infect human cells. Human cellular receptors exist for porcine endogenous retrovirus (PERV) which infects certain human-derived cell lines in vitro...
March 7, 2018: American Journal of Transplantation
Mickey S Ising, Michele Gallo, William M Whited, Mark S Slaughter, Jaimin R Trivedi
Recent reports have shown an increase in the number of organ donors from drug intoxication. The impact of donor drug use on survival after cardiac transplant remains unclear. The aim of our study was to illustrate changes in donor death mechanisms and assess the impact on post-transplant survival. We queried United Network of Organ Sharing thoracic transplant and deceased donor databases to identify patients undergoing heart transplantation between 2005 and 2015. We evaluated annual trends in donor death mechanisms...
March 7, 2018: American Journal of Transplantation
C L Jay, M M Abecassis
For decades, evidence has been available demonstrating the superiority of kidney transplantation for patients with end-stage renal disease (ESRD) compared with dialysis in terms of improved survival, better quality of life, and long-term cost-effectiveness.(1, 2) Yet, many barriers continue to exist to increasing patient access to kidney transplant through utilization of higher risk deceased donor kidney transplants (DDKT) or blood type (ABO) or immunologically (HLA) incompatible living donor kidney transplants (LDKT)...
March 7, 2018: American Journal of Transplantation
R A Bray, H M Gebel, R Townsend, M E Roberts, M Polinsky, L Yang, H-U Meier-Kriesche, C P Larsen
Donor-specific antibodies (DSAs) are associated with an increased risk of antibody-mediated rejection and graft failure. In BENEFIT and BENEFIT-EXT, kidney transplant recipients were randomized to receive belatacept more intense (MI)-based, belatacept less intense (LI)-based, or cyclosporine-based immunosuppression for up to 7 years (84 months). The presence/absence of HLA-specific antibodies was determined at baseline, at months 6, 12, 24, 36, 48, 60, and 84, and at the time of clinically suspected episodes of acute rejection, using solid-phase flow cytometry screening...
March 6, 2018: American Journal of Transplantation
Shinji Okano, Kareem Abu-Elmagd, Danielle D Kish, Karen Keslar, William M Baldwin, Robert L Fairchild, Masato Fujiki, Ajai Khanna, Mohammed Osman, Guilherme Costa, John Fung, Charles Miller, Hiroto Kayashima, Koji Hashimoto
Recent advances in immunosuppressive regimens have decreased acute cellular rejection (ACR) rates and improved intestinal transplant (ITx) recipient survival. We investigated the role of myeloid-derived suppressor cells (MDSCs) in ITx. We identified MDSCs as CD33+ CD11b+ lineage(CD3/CD56/CD19)- HLA-DR-/low cells with 3 subsets, CD14- CD15- (e-MDSC), CD14+ CD15- (M-MDSC), and CD14- CD15+ (PMN-MDSC), in peripheral blood mononuclear cells (PBMCs) and mononuclear cells in the grafted intestinal mucosa. Total MDSC numbers increased in PBMCs following ITx; among MDSC subsets, M-MDSC numbers were maintained at high level after 2 months following ITx...
March 6, 2018: American Journal of Transplantation
Paulo N Martins, Margaux N Mustian, Paul A MacLennan, Jorge A Ortiz, Mohamed Akoad, Juan Carlos Caicedo, Gabriel J Echeverri, Stephen H Gray, Reynold I Lopez-Soler, Ganesh Gunasekaran, Beau Kelly, Constance M Mobley, Sylvester M Black, Carlos Esquivel, Jayme E Locke
Blood group B candidates, many of whom represent ethnic minorities, have historically had diminished access to deceased donor kidney transplantation (DDKT). The new national kidney allocation system (KAS) preferentially allocates blood group A2/A2B deceased donor kidneys to B recipients to address this ethnic and blood group disparity. No study has yet examined the impact of KAS on A2 incompatible (A2i) DDKT for blood group B recipients overall or among minorities. A case-control study of adult blood group B DDKT recipients from 2013-2017 was performed, as reported to the Scientific Registry of Transplant Recipients...
March 6, 2018: American Journal of Transplantation
Gilles Benichou, Aurore Prunevieille
Recipient pro-inflammatory T cells recognizing donor MHC molecules in a direct fashion trigger early acute rejection of cardiac allografts. In clinical settings, prevention of acute rejection is regularly achieved via continuous suppression of these T cells using immunosuppressive drugs, including calcineurin inhibitors. Nevertheless, within 5 years post-transplantation, up to 50% patients suffer late cardiac allograft failure whose major pathological manifestation is chronic allograft vasculopathy (CAV). CAV is characterized by intimal thickening, smooth muscle cell proliferation, and accumulation of extracellular matrix, which result in arterial narrowing and eventually graft ischemia and fibrosis...
March 5, 2018: American Journal of Transplantation
Qi Cheng, Kunal Patel, Biao Lei, Lindsay Rucker, D Patterson Allen, Peng Zhu, Chentha Vasu, Paulo N Martins, Martin Goddard, Satish N Nadig, Carl Atkinson
Donor brain death (BD) is an inherent part of lung transplantation (LTx) and a key contributor to ischemia-reperfusion injury (IRI). Complement activation occurs as a consequence of BD in other solid organ Tx and exacerbates IRI, but the role of complement in LTx has not been investigated. Here, we investigate the utility of delivering nebulized C3a receptor antagonist (C3aRA) pre-Transplant to BD donor lungs in order to reduce post-LTx IRI. BD was induced in Balb/c donors, and lungs nebulized with C3aRA or vehicle 30 minutes prior to lung procurement...
March 5, 2018: American Journal of Transplantation
John S Gill
In this issue of the Journal two studies advance understanding of the risk of ESRD in prior living donors. Wainright and colleagues provide the most rigorous national analysis of the incidence of end stage renal disease (ESRD) in living kidney donors in the published literature (1). Despite the availability of donor records since 1987 in the United States, the study was limited to donations after April 1994 when donor social security numbers were recorded to facilitate ascertainment of future deaths and ESRD events by linkage to national data sets including the Social Security Death Master File and the Center of Medicare and Medicaid Services (CMS) 2728 file...
March 2, 2018: American Journal of Transplantation
Jason S Hawksworth, Chirag S Desai, Khalid M Khan, Stuart S Kaufman, Nada Yazigi, Raffaele Girlanda, Alexander Kroemer, Thomas M Fishbein, Cal S Matsumoto
Intestine failure-associated liver disease (IFALD) is widely recognized as a lethal complication of long-term parenteral nutrition. The pathophysiology of IFALD is poorly understood but appears to be multifactorial and related to the inflammatory state in the patient with intestinal failure (IF). Visceral transplantation for IFALD includes variants of intestine, liver, or combined liver and intestine transplantation. Graft selection for an individual patient depends on the etiology of intestinal failure, abdominal and vascular anatomy, severity of IFALD, and potential for intestinal rehabilitation...
March 2, 2018: American Journal of Transplantation
Otto A Sanchez, Laine K Ferrara, Sarah Rein, Danielle Berglund, Arthur J Matas, Hassan N Ibrahim
Incidence of post-donation hypertension, risk factors associated with its development and impact of type of treatment received on renal outcomes were determined in 3700 kidney donors. Using Cox proportional hazard model, adjusted hazard ratios (HRs) for cardiovascular disease (CVD), estimated glomerular filtration rate (eGFR) <60, <45, <30 mL/min/1.73m2 , end stage renal disease (ESRD) and death in hypertensive donors were determined. After a mean (SD) of 16.6 (11.9) years of follow-up, 1126 (26.8%) donors developed hypertension and 894 were receiving anti-hypertensive medications...
March 2, 2018: American Journal of Transplantation
J Reinier F Narvaez, Jing Nie, Katia Noyes, Mary Leeman, Liise K Kayler
Understanding risk factors for deceased-donor kidney non-transplantation is important since discard rates remain high. We analyzed DonorNet® data of consecutive deceased-donor non-mandatory share primary kidney-only offers to adult candidates at our center and beyond between July 1, 2015 and March 31, 2016 for donor- and system-level risk factors of discard, defined as non-transplantation at our or subsequent transplant centers. Exclusions were HCV/HBV, blood type AB, and donor< 1 year based on low candidate waitlist size...
March 2, 2018: American Journal of Transplantation
K L Lentine, N N Lam, A S Naik, D A Axelrod, Z Zhang, V R Dharnidharka, G P Hess, D L Segev, R Ouseph, H Randall, T Alhamad, R Devraj, R Gadi, B L Kasiske, D C Brennan, M A Schnitzler
Evolving literature suggests that the epidemic of prescription opioid use affects the transplant population. We examined a novel database wherein national U.S. transplant registry records were linked to a large pharmaceutical claims warehouse (2007 to 2015) to characterize prescription opioid use before and after kidney transplant, and associations (adjusted hazard ratio,95% LCL aHR95% UCL ) with death and graft loss. Among 75,430 eligible patients, 43.1% filled opioids in the year before transplant. Use was more common among recipients who were women, white, unemployed, publicly insured, and with longer pre-transplant dialysis...
March 2, 2018: American Journal of Transplantation
M L Arnold, A Kainz, L G Hidalgo, F Eskandary, N Kozakowski, M Wahrmann, H Haslacher, R Oberbauer, A Heilos, B M Spriewald, P F Halloran, G A Böhmig
Fc-dependent effector mechanisms may contribute to antibody-mediated rejection (ABMR), and distinct gene polymorphisms modifying the function of Fc gamma receptors (FcγR) may potentially influence the capability of donor-specific antibodies (DSA) to trigger inflammation. To evaluate the relevance of functional FcγR variants in late ABMR, 85 DSA-positive kidney allograft recipients, who were recruited upon antibody screening of 741 prevalent patients, were genotyped for polymorphisms in FcγRIIA (FCGR2A-H/R131 ; rs1801274), FcγRIIIA (FCGR3A-V/F158 ; rs396991) and FcγRIIIB [FCGR3B-neutrophil antigen 1 (NA1)/NA2; rs35139848]...
February 25, 2018: American Journal of Transplantation
Michael J Englesbe
In this issue of AJT, Querard et al. estimate the population average effect of graft loss of an Extended Criteria Donor (ECD) kidney compared to Standard Criteria Donor (SCD) kidney (1). This manuscript can be best summarized as… "Maybe ECD kidneys aren't as bad as I thought?" The well-established hazard ratio (HR) for graft loss associated with an ECD kidney, compared to an SCD kidney, is 1.7 (2). This number is derived from the standard population-based survival analysis in which relevant donor and recipient covariates are included in a Cox proportional hazards model...
February 25, 2018: American Journal of Transplantation
Antonio Bruni, Andrew R Pepper, Rena L Pawlick, Boris Gala-Lopez, Anissa Gamble, Tatsuya Kin, Andrew J Malcolm, Carissa Jones, Jon D Piganelli, James D Crapo, A M James Shapiro
Islet transplantation has become a well-established therapy for select patients suffering from type 1 diabetes. Viability and engraftment can be compromised by the generation of oxidative stress encountered during isolation and culture. We evaluate whether administration of BMX-001, and its earlier derivative, BMX-010 could improve islet function and engraftment outcomes. Long-term culture of human islets with BMX-001, but not BMX-010, exhibited preserved in vitro viability. Murine islets isolated and cultured for 24 hours with 34μM BMX-001 exhibited improved insulin secretion (n=3 isolations, p<0...
February 21, 2018: American Journal of Transplantation
Shoichi Kageyama, Kojiro Nakamura, Bibo Ke, Ronald W Busuttil, Jerzy W Kupiec-Weglinski
Liver ischemia-reperfusion injury (IRI) represents a risk factor for early graft dysfunction and an obstacle to expanding donor pool in orthotopic liver transplantation (OLT). We have reported on the crucial role of macrophage Notch1 signaling in mouse warm hepatic IRI model. However, its clinical relevance or therapeutic potential remain unknown. Here, we used Serelaxin (SER), to verify Notch1 induction and putative hepatoprotective function in IR-stressed OLT. C57BL/6 mouse livers subjected to extended (18hr) cold storage were transplanted to syngeneic recipients...
February 21, 2018: American Journal of Transplantation
H L Stevenson, M M Prats, K Isse, A Zeevi, Y Avitzur, V L Ng, A J Demetris
According to the Banff criteria for kidney allografts, isolated vascular or "v" lesions are defined as intimal inflammation, age-inappropriate fibro-intimal hyperplasia, or both, without the presence of associated interstitial T cell-mediated rejection (TCMR). In general, these lesions portend a worse outcome for kidney allografts, particularly in those where the "v" lesions are identified in patients with co-existent donor specific antibodies (DSA) or later after transplantation. Although affected arteries are rarely sampled in liver allograft biopsies, we identified 9 patients at a mean of 1,805 days post-transplantation and compared these to matched controls...
February 21, 2018: American Journal of Transplantation
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