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https://www.readbyqxmd.com/read/29225802/effective-immunosuppressive-management-with-belatacept-and-eculizumab-in-post-transplant-ahus-due-to-a-homozygous-deletion-of-cfhr1-cfhr3-and-the-presence-of-cfh-antibodies
#1
Johannes Münch, Anette Bachmann, Maik Grohmann, Christof Mayer, Michael Kirschfink, Tom H Lindner, Carsten Bergmann, Jan Halbritter
Atypical haemolytic uraemic syndrome (aHUS) may clinically present as acute renal graft failure resulting from excessive activation of the complement cascade. While mutations of complement-encoding genes predispose for aHUS, it is generally thought to require an additional insult (e.g. drugs) to trigger and manifest the full-blown clinical syndrome. Calcineurin inhibitors (CNIs) used for immunosuppression act as potential triggers, especially in the post-transplantation setting. Therefore, CNI-free immunosuppressive regimens may be beneficial...
December 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/29218048/commentary-belatacept-does-not-inhibit-follicular-t-cell-dependent-b-cell-differentiation-in-kidney-transplantation
#2
COMMENT
Paul M Schroder, Brian Ezekian, Mandy Ford, Stuart J Knechtle, Jean Kwun
No abstract text is available yet for this article.
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29157988/de-novo-thrombotic-microangiopathy-after-kidney-transplantation
#3
REVIEW
Neetika Garg, Helmut G Rennke, Martha Pavlakis, Kambiz Zandi-Nejad
Thrombotic microangiopathy (TMA) is a serious complication of transplantation that adversely affects kidney transplant recipient and allograft survival. Post-transplant TMA is usually classified into two categories: 1) recurrent TMA and 2) de novo TMA. Atypical hemolytic uremic syndrome (aHUS) resulting from dysregulation and over-activation of the alternate complement pathway is a rare disease but the most common diagnosis associated with recurrence in the allografts. De novo TMA, on the other hand, represents an overwhelming majority of the cases of post-transplant TMA and is a substantially more heterogeneous entity than recurrent aHUS...
November 4, 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/29136317/il-7-receptor-heterogeneity-as-a-mechanism-for-repertoire-change-during-post-depletional-homeostatic-proliferation-and-its-relation-to-costimulation-blockade-resistant-rejection
#4
He Xu, Victoria A Bendersky, Todd V Brennan, Jaclyn R Espinosa, Allan D Kirk
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...
November 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29123208/differential-t-cell-signaling-pathway-activation-by-tacrolimus-and-belatacept-after-kidney-transplantation-post-hoc-analysis-of-a-randomised-controlled-trial
#5
Nynke M Kannegieter, Dennis A Hesselink, Marjolein Dieterich, Gretchen N de Graav, Rens Kraaijeveld, Carla C Baan
Pharmacokinetic immunosuppressive drug monitoring poorly correlates with clinical outcomes after solid organ transplantation. A promising method for pharmacodynamic monitoring of tacrolimus (TAC) in T cell subsets of transplant recipients might be the measurement of (phosphorylated) p38MAPK, ERK1/2 and Akt (activated downstream of the T cell receptor) by phospho-specific flow cytometry. Here, blood samples from n = 40 kidney transplant recipients (treated with either TAC-based or belatacept (BELA)-based immunosuppressive drug therapy) were monitored before and throughout the first year after transplantation...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29084026/cause-for-cautious-optimism-belatacept-for-patients-with-impaired-kidney-allograft-function
#6
John S Gill
No abstract text is available yet for this article.
October 27, 2017: Transplantation
https://www.readbyqxmd.com/read/29077658/early-conversion-to-belatacept-in-kidney-transplant-recipient-with-low-glomerular-filtration-rate
#7
Dina Abdelwahab Elhamahmi, Raymond L Heilman, Byron Smith, Janna Huskey, Hasan Khamash, Bruce Kaplan
BACKGROUND: Our aim was to determine the impact of converting from tacrolimus to belatacept in patients with stable low eGFR early after kidney transplant. METHODS: This is a single center retrospective case control study. During this study period we had a clinical protocol to convert patients to belatacept if they had a stable but low GFR and they were at least 1-month posttransplant. Eligible patients had stable but low eGFR usually < 40 ml/min/1.73m2. We used direct matching to select 1 control case for each patient converted to belatacept...
October 26, 2017: Transplantation
https://www.readbyqxmd.com/read/29069245/belatacept-in-kidney-transplantation-past-and-future-perspectives
#8
Zaki Siddiqui, Hélio Tedesco-Silva, Leonardo V Riella
Calcineurin inhibitors (CNIs) are used widely for maintenance immunosuppression in renal transplant recipients. However, their side effect profile has led researchers to attempt to find safer alternatives that can maintain effective long-term immunosuppression with less toxicity. Belatacept is a CTLA4-Ig molecule designed to block the costimulatory B7-CD28 signal needed for activation of effector T cells. While it has shown great promise in clinical trials, it has made halting progress towards replacing CNIs in actual clinical practice...
April 2017: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/29057561/pre-clinical-results-in-pig-to-non-human-primate-islet-xenotransplantation-using-anti-cd40-antibody-2c10r4-based-immunosuppression
#9
Jun-Seop Shin, Jong-Min Kim, Byoung-Hoon Min, Il Hee Yoon, Hyun Je Kim, Jung-Sik Kim, Yong-Hee Kim, Seong-Jun Kang, Jiyeon Kim, Hee-Jung Kang, Dong-Gyun Lim, Eung-Soo Hwang, Jongwon Ha, Sang-Joon Kim, Wan Beom Park, Chung-Gyu Park
BACKGROUND: Islet transplantation is an effective therapy for selected patients with type 1 diabetes with labile glycemic control and hypoglycemic unawareness, but donor organs are limited. Islet xenotransplantation using porcine islets will potentially solve this problem. Although successful proof of concept studies using clinically inapplicable anti-CD154 monoclonal antibody (mAb) in pig-to-non-human primate (NHP) islet xenotransplantation has been demonstrated by several groups worldwide, potentially clinically applicable anti-CD40 (2C10R4) mAb-based studies have not been reported...
October 22, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29027667/co-inhibitory-profile-and-cytotoxicity-of-cd57-pd-1-t-cells-in-end-stage-renal-disease-patients
#10
Rens Kraaijeveld, Gretchen N de Graav, Marjolein Dieterich, Nicolle H R Litjens, Dennis A Hesselink, Carla C Baan
Blockade of the CD80/86-CD28 pathway by belatacept after kidney transplantation is associated with an increased risk of rejection as compared with standard, calcineurin inhibitor (CNI)-based therapy. CD28(-) T-cells, which express CD57, are not susceptible to belatacept treatment. High number of CD4(+) CD57(+) PD-1(-) T-cells pre transplantation have been associated with a higher chance of rejection, although conflicting data have been reported. To investigate the working mechanism behind this possible higher chance of rejection, we studied the expression of co-inhibitory molecules (CD223, CD244 and PD-1), proliferative capacity and cytotoxic potential of FACS-sorted CD4(+) CD57(+) PD-1(-) and CD8(+) CD57(+) PD-1(-) T-cells, and their CD57(-) control populations, after allo antigen stimulation...
October 13, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28970838/successful-treatment-of-t-cell-mediated-acute-rejection-with-delayed-ctla4-ig-in-mice
#11
James S Young, Stella H-W Khiew, Jinghui Yang, Augustin Vannier, Dengping Yin, Roger Sciammas, Maria-Luisa Alegre, Anita S Chong
Clinical observations that kidney transplant recipients receiving belatacept who experienced T cell-mediated acute rejection can be successfully treated and subsequently maintained on belatacept-based immunosuppression suggest that belatacept is able to control memory T cells. We recently reported that treatment with CTLA4-Ig from day 6 posttransplantation successfully rescues allografts from acute rejection in a BALB/c to C57BL/6 heart transplant model, in part, by abolishing B cell germinal centers and reducing alloantibody titers...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28923620/late-conversion-to-belatacept-after-kidney-transplantation-outcome-and-prognostic-factors
#12
M Dürr, N Lachmann, B Zukunft, D Schmidt, K Budde, S Brakemeier
BACKGROUND: Conversion to belatacept at a later point after kidney transplantation (KT) as a rescue therapy has been shown to be beneficiary in an increasing number of patients, but prognostic factors for a favorable outcome have never been investigated. METHODS: The present study analyzed all KT patients after late conversion to belatacept in a single center regarding graft survival and changes in estimated glomerular filtration rate (eGFR), proteinuria, and mean fluorescence intensity (MFI) of donor-specific antibodies (DSA)...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28873970/immunosuppressive-agents-in-adult-kidney-transplantation-in-the-national-health-service-a-model-based-economic-evaluation
#13
Tristan M Snowsill, Jason Moore, Ruben E Mujica Mota, Jaime L Peters, Tracey L Jones-Hughes, Nicola J Huxley, Helen F Coelho, Marcela Haasova, Chris Cooper, Jenny A Lowe, Jo L Varley-Campbell, Louise Crathorne, Matt J Allwood, Rob Anderson
Background: Immunosuppression is required in kidney transplantation to prevent rejection and prolong graft survival. We conducted an economic evaluation to support England's National Institute for Health and Care Excellence in developing updated guidance on the use of immunosuppression, incorporating new immunosuppressive agents, and addressing changes in pricing and the evidence base. Methods: A discrete-time state transition model was developed to simulate adult kidney transplant patients over their lifetime...
July 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28805142/intravenous-immunoglobulins-modify-relapsing-membranous-glomerulonephritis-after-kidney-transplantation-a-case-report
#14
Sanne Steyaert, Jo Van Dorpe, Anne Hoorens, Wim Van Biesen, Steven Van Laecke
OBJECTIVES: Recurrence of membranous glomerulonephritis after transplant is common and is an important cause of loss of renal graft. This case supports the effect of immunoglobulins in the treatment of this disease after transplantation. It is the first report in the literature with a follow-up of more than 10 years and because of the sustained effect of the immunoglobulins, it strengthens the idea that this can alter long-term outcome. METHODS: Single case study and search of the literature...
August 14, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28758341/ten-year-outcomes-in-a-randomized-phase-ii-study-of-kidney-transplant-recipients-administered-belatacept-4-weekly-or-8-weekly
#15
F Vincenti, G Blancho, A Durrbach, G Grannas, J Grinyó, H-U Meier-Kriesche, M Polinsky, L Yang, C P Larsen
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...
December 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28742936/benefits-and-limitations-of-belatacept-in-4-hand-transplanted-patients
#16
J Grahammer, A Weissenbacher, B G Zelger, B Zelger, C Boesmueller, M Ninkovic, A Mühlbacher, I Peschel, G Brandacher, D Öfner, S Schneeberger
Belatacept (cytotoxic T-lymphocyte-associated protein 4 Ig) is an emerging treatment in kidney transplantation. Lack of nephrotoxicity and possibly an inhibitory effect on the development of donor-specific antibodies (DSAs) make it an interesting agent in hand transplantation. To reduce calcineurin inhibitor immunosuppression and preserve kidney function, we have added belatacept to the therapeutic regimen of 4 hand-transplanted patients at month 4 and at 6, 9, and 13 years after hand-forearm transplantation...
December 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28717935/rabbit-anti-human-thymocyte-immunoglobulin-for-the-rescue-treatment-of-chronic-antibody-mediated-rejection-after-pediatric-kidney-transplantation
#17
Yasemen Cihan, Nele Kanzelmeyer, Jens Drube, Martin Kreuzer, Christian Lerch, Imke Hennies, Kerstin Froede, Murielle Verboom, Thurid Ahlenstiel-Grunow, Lars Pape
BACKGROUND: Chronic antibody-mediated rejection (cAMR) is the leading cause of late kidney graft loss, but current therapies are often ineffective. Rabbit anti-human thymocyte immunoglobulin (rATG) may be helpful, but its use is virtually undocumented. METHODS: Data were analyzed retrospectively from nine pediatric kidney transplant patients with cAMR were treated with rATG (1.5 mg/kg × 5 days) at our center after non-response to pulsed prednisolone, intravenous immunoglobulin, rituximab, and increased immunosuppressive intensity (including switching to belatacept in some cases), with or without bortezomib...
November 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28708266/belatacept-conversion-in-an-hiv-positive-kidney-transplant-recipient-following-anti-thymocyte-globulin-induction
#18
Samantha A Kuten, Samir J Patel, Ashvin Baru, A Osama Gaber, Rustin D Crutchley, Venkataraman Ramanathan, Richard J Knight
Herein, we describe a case of early belatacept conversion in a human immunodeficiency virus (HIV)-positive kidney transplant recipient in an effort to improve suboptimal graft function and avoid drug interactions following anti-thymocyte globulin (ATG) administration. We observed improvement in renal function without HIV disease progression or opportunistic infections. Donor-specific antibodies appeared shortly after conversion but cleared without intervention. This case highlights belatacept as a means to improve renal function and avoid significant drug interactions even following ATG induction...
July 14, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28707779/belatacept-rescue-therapy-in-kidney-transplant-recipients-with-vascular-lesions-a-case-control-study
#19
D Bertrand, L Cheddani, I Etienne, A François, M Hanoy, C Laurent, L Lebourg, F Le Roy, L Lelandais, M C Loron, M Godin, D Guerrot
Immunosuppression in kidney transplant recipients with decreased graft function and severe histological vascular changes can be particularly challenging. Belatacept could be a valuable option, as a rescue therapy in this context. We report a retrospective case control study comparing a CNI to belatacept switch in 17 patients with vascular damage and low eGFR to a control group of 18 matched patients with CNI continuation. Belatacept switch was performed on average 51.5 months after kidney transplantation (6...
July 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28691954/maintenance-belatacept-based-immunosuppression-in-lung-transplantation-recipients-who-failed-calcineurin-inhibitors
#20
Carlo J Iasella, Ryan J Winstead, Cody A Moore, Bruce A Johnson, Ayelet T Feinberg, Matthew R Morrell, J W Awori Hayanga, Elizabeth A Lendermon, Adriana Zeevi, John F McDyer, Christopher R Ensor
BACKGROUND: Traditional immunosuppressive regimens (ISR) used in lung transplantation rely on calcineurin inhibitors (CNI) that occasionally cause severe adverse reactions necessitating discontinuation. Belatacept is a novel costimulation antagonist approved for use in renal transplantation which lacks data in lung transplantation. This series aims to describe the response to belatacept ISR in 11 lung transplantation recipients after CNI failure. METHODS: Single center, retrospective medical record review of adult lung transplant recipients (LTR) before and after conversion to belatacept-based ISR...
July 6, 2017: Transplantation
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