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https://www.readbyqxmd.com/read/28544604/thymic-peripheral-crosstalk-in-lymphodepletion-therapy
#1
EDITORIAL
M E Snyder, D L Farber
T cell depletion is widely used as induction therapy in solid organ transplants and particularly in kidney transplantation, to reduce the episodes of acute cellular rejection. The resultant reduction in T cell numbers is usually temporary, as T cells are actively replenished due to thymic output and/or lymphopenia-induced proliferation of remaining, depletion-resistant T cells. However, the extent of T cell replenishment and the persistence of lymphopenia varies between individuals, with potential impacts on protective or pathogenic immune responses...
May 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28544101/belatacept-combined-with-transient-calcineurin-inhibitor-therapy-prevents-rejection-and-promotes-improved-long-term-renal-allograft-function
#2
A B Adams, J Goldstein, C Garrett, R Zhang, R E Patzer, K A Newell, N A Turgeon, A S Chami, A Guasch, A D Kirk, S O Pastan, T C Pearson, C P Larsen
Belatacept, a T cell costimulation-blocker demonstrated superior renal function, lower cardiovascular risk, and improved graft/patient survival in renal transplant recipients. Despite the potential benefits, adoption of belatacept has been limited in part due to concerns regarding higher rates and grades of acute rejection in clinical trials. Since July 2011 we have utilized belatacept-based immunosuppression regimens in clinical practice. In this retrospective analysis of 745 patients undergoing renal transplantation at our center, we compared patients treated with belatacept (n=535) to a historical cohort receiving a tacrolimus-based protocol (n=205)...
May 23, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28540602/late-conversion-from-tacrolimus-to-a-belatacept-based-immuno-suppression-regime-in-kidney-transplant-recipients-improves-renal-function-acid-base-derangement-and-mineral-bone-metabolism
#3
Kevin Schulte, Clara Vollmer, Vera Klasen, Jan Hinrich Bräsen, Jodok Püchel, Christoph Borzikowsky, Ulrich Kunzendorf, Thorsten Feldkamp
BACKGROUND: Calcineurin inhibitor (CNI)-induced nephrotoxicity and chronic graft dysfunction with deteriorating glomerular filtration rate (GFR) are common problems of kidney transplant recipients. The aim of this study was to analyze the role of belatacept as a rescue therapy in these patients. METHODS: In this retrospective, observational study we investigated 20 patients (10 females, 10 males) who were switched from a CNI (tacrolimus) to a belatacept-based immunosuppression because of CNI intolerance or marginal transplant function...
May 24, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28538050/molecular-imaging-of-acute-cardiac-transplant-rejection-animal-experiments-and-prospects
#4
Yihan Chen, Li Zhang, Jinfeng Liu, Pingyu Zhang, Xiaoyuan Chen, Mingxing Xie
Acute rejection (AR) remains the biggest challenge during the 1st year after heart transplantation despite advances in immunosuppressive therapy. The early detection and curbing of AR are crucial to the survival of transplant recipients. However, as the gold standard for AR, endomyocardial biopsy has several limitations because of its inherent invasiveness and morbidity. Traditional imaging techniques such as echocardiography and cardiac magnetic resonance imaging are of certain value for AR, but their diagnostic criteria and accuracy remain in question...
May 19, 2017: Transplantation
https://www.readbyqxmd.com/read/28535527/treatment-of-acute-antibody-mediated-rejection
#5
Giorgia Comai, Matteo Ravaioli, Olga Baraldi, Vania Cuna, Lorenzo Gasperoni, Giovanni Liviano D''Arcangelo, Maria Cappuccilli, Antonio D Pinna, Claudio Ronco, Gaetano La Manna
Acute antibody-mediated rejection (AMR) remains an important challenge in the field of kidney transplantation despite the advances in immunosuppressive strategies, and has been recognized as an important cause of allograft dysfunction and graft loss. The treatments of acute AMR are not standardized and poor evidence is currently available on the effectiveness of therapy regimens with combinations of drugs. Standard treatment for acute AMR is based on 3 cornerstones: removal of donor-specific antibodies (DSAs) from the bloodstream, reduction of DSAs synthesis, and inhibition of the interaction between DSAs and human leukocyte antigen antigens on donor's cells...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28532691/bio-synthetic-materials-for-immunomodulation-of-islet-transplants
#6
Greg A Foster, Andrés J García
Clinical islet transplantation is an effective therapy in restoring physiological glycemic control in type 1 diabetics. However, allogeneic islets derived from cadaveric sources elicit immune responses that result in acute and chronic islet destruction. To prevent immune destruction of islets, transplant recipients require lifelong delivery of immunosuppressive drugs, which are associated with debilitating side effects. Biomaterial-based strategies to eliminate the need for immunosuppressive drugs are an emerging therapy for improving islet transplantation...
May 19, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28508573/regional-differences-in-the-management-and-outcome-of-kidney-transplantation-in-patients-with-human-immunodeficiency-virus-infection-a-3-year-retrospective-cohort-study
#7
Marina P Cristelli, Federico Cofán, Helio Tedesco-Silva, Joan Carles Trullàs, Daniel Wagner C L Santos, Cristian Manzardo, Fernando Agüero, Asunción Moreno, Federico Oppenheimer, Fritz Diekmann, Jose O Medina-Pestana, Jose Maria Miro
BACKGROUND: In the developed world, kidney transplantation (KT) in patients with human immunodeficiency virus (HIV) infection is well established. Developing countries concentrate 90% of the people living with HIV, but their experience is underreported. Regional differences may affect outcomes. OBJECTIVES: We compared the 3-year outcomes of patients with HIV infection receiving a KT in two different countries, in terms of incomes and development. METHODS: This was an observational, retrospective, double-center study, including all HIV-infected patients >18 years old undergoing KT...
May 16, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28504842/safety-and-efficacy-of-current-daa-regimens-in-kidney-and-liver-transplant-recipients-with-hepatitis-c-results-from-the-hcv-target-study
#8
Varun Saxena, Vandana Khungar, Elizabeth C Verna, Josh Levitsky, Robert S Brown, Mohamed A Hassan, Mark S Sulkowski, Jacqueline G O'Leary, Farrukh Koraishy, Joseph S Galati, Alexander A Kuo, Monika Vainorius, Lucy Akushevich, David R Nelson, Michael W Fried, Norah Terrault, K Rajender Reddy
BACKGROUND: Data outside of clinical trials with direct acting antiviral (DAA) regimens with or without ribavirin as treatment of chronic HCV in solid organ transplant recipients is limited. METHODS: Liver transplant (LT), kidney transplant (KT) and dual liver kidney (DLK) transplant recipients from the HCV-TARGET database, a multicenter, longitudinal clinical care treatment cohort, treated with DAA regimens between January 1 2014 and February 15, 2016 were included to assess safety and efficacy...
May 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28503959/emerging-drugs-for-prevention-of-t-cell-mediated-rejection-in-liver-and-kidney-transplantation
#9
Tiffany Cl Wong, Chung-Mau Lo, James Yy Fung
Acute and chronic graft rejection continues to be an important problem after solid organ transplantation. With the introduction of potent immunosuppressive agents such as calcineurin inhibitors, the risk of rejection has been significantly reduced. However, the adverse effects of life-long immunosuppression remain a concern, and there exist a fine balance between over-immunosuppression and risk of rejection. Areas covered. In this review, the current standard of care in immunosuppressive therapy, including the use of steroids, calcineurin inhibitors, mycophenolate prodrugs and mammalian target of rapamycin inhibitors, will be discussed...
May 15, 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28501036/tuberculosis-in-liver-transplant-recipients-a-report-of-eight-cases-during-a-five-year-period
#10
Diana Póvoas, João Machado, Rui Perdigoto, Ana Morbey, Júlio Veloso, Helena Glória, Élia Mateus, Américo Martins, Fernando Maltez, Eduardo Barroso
INTRODUCTION: Tuberculosis incidence in Portugal ranged from 20 to 22 cases per 100 000 inhabitants between 2010 and 2014. Tuberculosis incidence in liver transplant recipients is not precisely known, but it is estimated to be higher than among the general population. Tuberculosis in liver transplant recipients is particularly challenging because of the atypical clinical presentation and side effects of the antibacillary drugs and their potential interactions with immunosuppressive therapies...
January 31, 2017: Acta Médica Portuguesa
https://www.readbyqxmd.com/read/28494654/new-formulations-of-tacrolimus-and-prevention-of-acute-and-chronic-rejections-in-adult-kidney-transplant-recipients
#11
Lionel Rostaing, Thomas Jouve, Paolo Malvezzi
BACKGROUND: As tolerance is not yet achievable, the kidney-transplanted-patients have to take on a daily-basis immunosuppressive drugs in order to avoid acute rejection-AR-. The cornerstone of immunosuppression relies on tacrolimus-therapy which is potentially nephrotoxic. RESEARCH DESIGN AND METHODS: We identified from the studies published in the recent years those who were reporting on AR in de novo kidney-transplant recipients under tacrolimus-based therapy, as well as those who reported on the attempt to minimize tacrolimus-therapy...
May 11, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28493630/clinical-outcomes-of-abo-and-hla-incompatible-kidney-transplantation-a-nationwide-cohort-study
#12
Eun Jeong Ko, Ji Hyun Yu, Chul Woo Yang, Byung Ha Chung
This was a nationwide cohort study to investigate the impact of anti-A/B and donor-specific anti-HLA (HLA-DSA) antibodies on the clinical outcomes in kidney transplant recipients (KTRs). We classified a total of 1,964 KTRs into four groups: transplants from ABO-incompatible donors (ABOi, n=248); transplants in recipients with HLA-DSA (HLAi, n=144); transplants from combined ABOi and HLAi donors (ABOi+HLAi, n=31); and a control group for whom neither ABOi nor HLAi was applicable (CONT, n=1541). We compared the incidence of biopsy proven acute rejection (BPAR), allograft and patient survival rates...
May 11, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28475563/depleting-antibody-induction-and-kidney-transplant-outcomes-a-paired-kidney-analysis
#13
Marcelo S Sampaio, Bhavna Chopra, Kalathil K Sureshkumar
BACKGROUND: Induction immunosuppression decreases the risk for acute rejection and improves graft outcomes in kidney transplant recipients (KTRs). We aimed to compare the outcomes of induction with Thymoglobulin and alemtuzumab in KTRs through paired-kidney analysis. METHODS: Using OPTN/UNOS database from 2003 to 2013, we identified recipients of deceased donor kidneys from the same donor in such a way that 1 patient received Thymoglobulin induction and recipient of the mate kidney underwent alemtuzumab induction...
October 11, 2016: Transplantation
https://www.readbyqxmd.com/read/28475248/effectiveness-of-an-evidence-based-induction-therapy-protocol-revision-in-adult-kidney-transplant-recipients
#14
Jillian P Casale, Dave J Taber, Carmelina Staino, Kimberly Boyle, Kelly Covert, Nicole A Pilch, Caitlin Mardis, Holly B Meadows, Kenneth D Chavin, John W McGillicuddy, Prabhakar K Baliga, James N Fleming
STUDY OBJECTIVE: Induction immunosuppression significantly improves graft outcomes following kidney transplantation, but protocols vary among transplant centers due to the lack of data identifying an optimal induction agent. The objective of this study was to assess the effectiveness of an evidence-based protocol change in induction therapy in adult kidney transplant recipients. DESIGN: Retrospective cohort study. SETTING: Large tertiary care academic medical center...
May 5, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28469082/ctla4-ig-in-combination-with-fty720-promotes-allograft-survival-in-sensitized-recipients
#15
Stella H Khiew, Jinghui Yang, James S Young, Jianjun Chen, Qiang Wang, Dengping Yin, Vinh Vu, Michelle L Miller, Roger Sciammas, Maria-Luisa Alegre, Anita S Chong
Despite recent evidence of improved graft outcomes and safety, the high incidence of early acute cellular rejection with belatacept, a high-affinity CTLA4-Ig, has limited its use in clinical transplantation. Here we define how the incomplete control of endogenous donor-reactive memory T cells results in belatacept-resistant rejection in an experimental model of BALB/c.2W-OVA donor heart transplantation into C57BL/6 recipients presensitized to donor splenocytes. These sensitized mice harbored modestly elevated numbers of endogenous donor-specific memory T cells and alloantibodies compared with naive recipients...
May 4, 2017: JCI Insight
https://www.readbyqxmd.com/read/28457410/immunomodulation-acute-renal-failure-and-complications-of-basiliximab-use-after-liver-transplantation-analysis-of-114-patients-and-literature-review
#16
E C de Ataide, S R Perales, J B Bortoto, M A O Peres, F C Filho, R S B Stucchi, E Udo, I F S F Boin
Basiliximab is considered to be effective in preventing cellular rejection (CR) in solid organ transplantation and is commonly used for renal transplants. The aim of this study was describe the population of patients undergoing orthotopic liver transplantation (LT) receiving basiliximab in the period 2012-2016 in the liver transplant service at the State University of Campinas, São Paulo, Brazil. We analyzed 114 patients who underwent LT and received basiliximab; 83 (72.8%) were male and 31 (27.2%) female, with an overall mean age of 54...
May 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28457402/early-vascular-thrombosis-after-kidney-transplantation-can-we-predict-patients-at-risk
#17
R A P de Freitas, M L de Lima, M Mazzali
BACKGROUND: Renal transplant is the therapy of choice for patients with chronic renal disease. In recent years, improvement in immunosuppressive drugs reduced early graft loss associated with acute rejection. However, vascular thrombosis, accounting for 5% of early graft loss, can sensitize the recipient for human leukocyte antibodies, reducing the chance for a second transplant. The aim of this study was to identify risk factors for vascular thrombosis in a single transplant center, to design specific prevention protocol...
May 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28448002/measurement-of-t-cell-alloreactivity-using-imaging-flow-cytometry
#18
Stephen C Juvet, Sajad Moshkelgosha, Sharon Sanderson, Joanna Hester, Kathryn J Wood, Andrew Bushell
The measurement of immunological reactivity to donor antigens in transplant recipients is likely to be crucial for the successful reduction or withdrawal of immunosuppression. The mixed leukocyte reaction (MLR), limiting dilution assays, and trans-vivo delayed-type hypersensitivity (DTH) assay have all been applied to this question, but these methods have limited predictive ability and/or significant practical limitations that reduce their usefulness. Imaging flow cytometry is a technique that combines the multiparametric quantitative powers of flow cytometry with the imaging capabilities of fluorescent microscopy...
April 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28435308/association-of-the-ppp3ca-c-249g-a-variant-with-clinical-outcomes-of-tacrolimus-based-therapy-in-kidney-transplant-recipients
#19
Patricia C Salgado, Fabiana Dv Genvigir, Claudia R Felipe, Helio Tedesco-Silva, Jose O Medina-Pestana, Sonia Q Doi, Mario H Hirata, Rosario Dc Hirata
BACKGROUND: The effects of genetic variants related to the pharmacodynamic mechanisms of immunosuppressive drugs on their therapeutic efficacy and safety have been poorly explored. This study was performed to investigate the influence of the PPP3CA c.249G>A variant on the clinical outcomes of kidney transplant recipients. PATIENTS AND METHODS: A total of 148 Brazilian patients received tacrolimus (TAC)-based immunosuppressive therapy for 90 days post-kidney transplantation...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28418009/effect-of-umod-genotype-on-long-term-graft-survival-after-kidney-transplantation-in-patients-treated-with-cyclosporine-based-therapy
#20
E Abdel-Hady Algharably, J Beige, R Kreutz, J Bolbrinker
The genetic rs12917707-G>T variant in uromodulin (UMOD) has been associated with renal function, chronic kidney disease and hypertension with the minor T-allele showing a protective effect. Hypertension and nephrotoxicity are adverse effects of chronic cyclosporine treatment. We tested whether UMOD rs12917707-T in donor kidneys associates with long-term graft survival in 393 Caucasian patients with stable graft function for more than 10 weeks after kidney transplantation treated with a cyclosporine-based maintenance therapy (mean graft survival 9 years)...
April 18, 2017: Pharmacogenomics Journal
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