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https://www.readbyqxmd.com/read/27862340/everolimus-with-early-withdrawal-or-reduced-dose-calcineurin-inhibitors-improves-renal-function-in-liver-transplant-recipients-a-systematic-review-and-meta-analysis
#1
Michael Lin, Sahil Mittal, Farhad Sahebjam, Abbas Rana, Gagan K Sood
Calcineurin inhibitors (CNI) are the mainstay of immunosuppression after liver transplantation (LT), but CNIs are associated with significant nephrotoxicity. Recently, mTOR inhibitors such as sirolimus and everolimus (EVR) have been used with or without CNIs in LT recipients for their renal-sparing effect. We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) that examined the effect of EVR with CNI minimization or withdrawal on renal function in LT recipients. RCT of primary adult LT recipients with baseline GFR >30 mL/min who received EVR with CNI minimization or withdrawal were included...
November 16, 2016: Clinical Transplantation
https://www.readbyqxmd.com/read/27659512/mtor-inhibitors-in-pancreas-transplant-adverse-effects-and-drug-drug-interactions
#2
Gabriel Fernandes-Silva, Mayara Ivani de Paula, Érika B Rangel
INTRODUCTION: Patient and pancreas allograft survival improved following reductions in surgical complications, tighter donor selection and optimization in immunosuppressive protocols. However, long-term survival of pancreas allografts is adversely affected by rejection and immunosuppressive regimen toxicity. AREAS COVERED: This article reviews the existing literature and knowledge of mammalian target of rapamycin inhibitors (mTORi). Some clinically relevant drug-drug interactions are highlighted...
September 23, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27564469/effect-of-mammalian-target-of-rapamycin-inhibitors-on-cytomegalovirus-infection-in-kidney-transplant-recipients-receiving-polyclonal-antilymphocyte-globulins-a-propensity-score-matching-analysis
#3
Carlos Cervera, Frederic Cofan, Cristina Hernandez, Dolors Soy, Maria Angeles Marcos, Gemma Sanclemente, Marta Bodro, Asunción Moreno, Fritz Diekmann, Josep Maria Campistol, Frederic Oppenheimer
Mammalian target of rapamycin inhibitors (mTORi) prevents cytomegalovirus (CMV) infection in kidney transplant (KT) patients. From May 2010 to December 2013, all KT recipients were retrospectively analysed. Maintenance immunosuppression regimen was divided into mTORi or calcineurin inhibitors (CNI)-based regimen. Since June 2011, CMV-seropositive recipients (R+) treated with high-intensity immunosuppression and mTORi did not receive anti-CMV prophylaxis. We analysed 350 consecutive patients, of which 95 (27%) received mTORi and 255 (73%) CNI-based immunosuppression...
August 26, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27514317/experience-with-belatacept-rescue-therapy-in-kidney-transplant-recipients
#4
Susanne Brakemeier, Dennis Kannenkeril, Michael Dürr, Tobias Braun, Friederike Bachmann, Danilo Schmidt, Michael Wiesener, Klemens Budde
In kidney transplant recipients with chronic graft dysfunction, long-term immunosuppression with calcineurin inhibitors (CNIs) or mTOR inhibitors (mTORi) can be challenging due to adverse effects, such as nephrotoxicity and proteinuria. Seventy-nine kidney transplant recipients treated with CNI-based or mTORi-based maintenance immunosuppression who had CNI-induced nephrotoxicity or severe adverse events were switched to belatacept. Mean time from transplantation to belatacept conversion was 69.0 months. Mean estimated glomerular filtration rate (eGFR) ± standard deviation at baseline was 26...
August 12, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27495768/use-of-everolimus-in-liver-transplantation-recommendations-from-a-working-group
#5
Paolo De Simone, Stefano Fagiuoli, Matteo Cescon, Luciano De Carlis, Giuseppe Tisone, Riccardo Volpes, Umberto Cillo
Immunosuppression after liver transplantation (LT) is presently based on use of calcineurin inhibitors (CNI), although they are associated with an increased incidence of renal dysfunction, cardiovascular complications, and de novo and recurrent malignancies. Over the past decade, mTOR inhibitors have received considerable attention as immunosuppressants as they are associated with a more favorable renal profile vs. CNI, as well as anti-proliferative activity in clinical studies. Comprehensive guidelines on use of everolimus (EVR) in LT are still lacking...
August 5, 2016: Transplantation
https://www.readbyqxmd.com/read/27362313/mtor-inhibition-suppresses-posttransplant-alloantibody-production-through-direct-inhibition-of-alloprimed-b-cells-and-sparing-of-cd8-antibody-suppressing-t-cells
#6
Christina L Avila, Jason M Zimmerer, Steven M Elzein, Thomas A Pham, Mahmoud Abdel-Rasoul, Ginny L Bumgardner
BACKGROUND: De novo alloantibodies (donor-specific antibody) contribute to antibody-mediated rejection and poor long-term graft survival. Because the development of donor-specific antibody is associated with early graft loss of cell transplants and reduced long-term survival of solid organ transplants, we hypothesized that conventional immunosuppressives, calcineurin inhibitors (CNi), and mammalian target of rapamycin inhibitors (mTORi), may not be as effective for suppression of humoral alloimmunity as for cell-mediated immunity...
September 2016: Transplantation
https://www.readbyqxmd.com/read/27293552/practical-considerations-for-the-use-of-mtor-inhibitors
#7
REVIEW
Fritz Diekmann, Josep M Campistol
Immunosuppressive therapy after kidney transplantation is based on calcineurin inhibitors (CNI). In most cases CNI therapy is combined with mycophenolate and steroids. In spite of good short-term results this therapy is associated with long-term toxicities, graft loss and patient death. Therefore, alternative immunosuppressive strategies are needed that combine excellent efficacy with low incidences of long-term adverse outcomes. This review focuses on the strategies based on mTOR- inhibitors in combination with minimized exposure to CNI...
2015: Transplantation Research
https://www.readbyqxmd.com/read/27109949/kidney-transplantation-in-hiv-infected-recipients-therapeutic-strategy-and-outcomes-in-monocentric-experience
#8
A Baisi, F Nava, B Baisi, E Rubbiani, G Guaraldi, F Di Benedetto, M Giovannoni, A Solazzo, D Bonucchi, G Cappelli
BACKGROUND: In Human immunodeficiency virus (HIV)-positive patients undergoing kidney transplantation, outcomes and immunosuppression (IS) protocol are not yet established due to infectious and neoplastic risks as well as to pharmacokinetic interactions with antiretroviral therapy (TARV). METHODS: We report a retrospective, 1-center study on 18 HIV+ patients undergoing, between October 2007 and September 2015, kidney transplantation (13 cases) or combined kidney-liver transplant (5 cases)...
March 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27083870/use-of-everolimus-in-liver-transplantation-the-french-experience
#9
REVIEW
Jérôme Dumortier, Sebastien Dharancy, Yvon Calmus, Christophe Duvoux, François Durand, Ephrem Salamé, Faouzi Saliba
The mammalian target of rapamycin (mTOR) inhibitor everolimus is approved for rejection prophylaxis after liver transplantation. The current article pools the experience of French liver transplant surgeons and physicians in use of everolimus and, particularly, practical guidance on dosing, appropriate concomitant immunosuppression and management of adverse events. In terms of indication, introduction of everolimus from week 4 after liver transplantation, with or without concomitant calcineurin inhibitor (CNI) therapy, offers a significant renal benefit without loss of immunosuppressive efficacy...
July 2016: Transplantation Reviews
https://www.readbyqxmd.com/read/26938682/wound-complications-and-surgical-events-in-de-novo-heart-transplant-patients-treated-with-everolimus-post-hoc-analysis-of-the-schedule-trial
#10
Mitra Rashidi, Sorosh Esmaily, Arnt E Fiane, Einar Gude, Kim A Tønseth, Thor Ueland, Finn Gustafsson, Hans Eiskjær, Göran Rådegran, Göran Dellgren
OBJECTIVES: The use of mammalian target of rapamycin (mTOR) inhibitors have been limited by adverse events (AE), including delayed wound healing. We retrospectively reviewed all AE and serious AE (SAE) in The Scandinavian heart transplant (HTx) everolimus (EVE) de novo trial with early calcineurin (CNI) avoidance (SCHEDULE). The aim of the study was to compare wound complications between EVE and CNI based regimen. MATERIALS AND METHODS: A total of 115 patients (mean age 51 ± 13 years, 73% men) were randomized within five days post-HTx to low dose EVE and reduced dose Cyclosporine (CyA) followed by early CyA withdrawal (EVE group; n=56) or standard CyA regimen (CyA group; n=59)...
May 1, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/26914542/a-randomized-prospective-comparison-of-transition-to-sirolimus-based-cni-minimization-or-withdrawal-in-african-american-kidney-transplant-recipients
#11
James N Fleming, David J Taber, Nicole A Pilch, John W McGillicuddy, Titte R Srinivas, Prabhakar K Baliga, Kenneth D Chavin, Charles F Bratton
BACKGROUND: There is a lack of conclusive evidence to suggest if calcineurin inhibitor (CNI) withdrawal or minimization with sirolimus is the best strategy for African Americans. METHODS: This was a randomized, prospective, open-label, pilot study comparing the two mammalian target of rapamycin (mTOR) transition strategies in adult African Americans between six and 24 wk post-transplant. The primary outcome was a comparison of the eGFR at one yr after conversion...
May 2016: Clinical Transplantation
https://www.readbyqxmd.com/read/26855333/selection-and-use-of-immunosuppressive-therapies-after-liver-transplantation-current-german-practice
#12
REVIEW
Kerstin Herzer, Christian P Strassburg, Felix Braun, Cornelius Engelmann, Markus Guba, Frank Lehner, Silvio Nadalin, Andreas Pascher, Marcus N Scherer, Andreas A Schnitzbauer, Tim Zimmermann, Björn Nashan, Martina Sterneck
In recent years, immunosuppression (IS) after liver transplantation (LT) has become increasingly diversified as the choice of agents has expanded and clinicians seek to optimize the balance of immunosuppressive potency with the risk of adverse events in individual patients. Calcineurin inhibitors (CNIs) are the primary agents used for patients undergoing liver transplantation. Other therapeutic agents like interleukin-2 receptor antagonists are not universally administered, but can be considered for the delay or reduction in CNI exposure...
May 2016: Clinical Transplantation
https://www.readbyqxmd.com/read/26836476/calcineurin-and-mtor-inhibitors-have-opposing-effects-on-regulatory-t-cells-while-reducing-regulatory-b-cell-populations-in-kidney-transplant-recipients
#13
Irene Latorre, Ana Esteve-Sole, Dolores Redondo, Sandra Giest, Jordi Argilaguet, Sara Alvarez, Cristina Peligero, Isabelle Forstmann, Marta Crespo, Julio Pascual, Andreas Meyerhans
BACKGROUND: Regulatory B (Breg) and T (Treg) cells represent a biomarker for tolerance in transplant patients. Despite the importance of Treg and Breg in transplantation and the suggested crosstalk between both suppressive cell populations, little is known on how they are influenced by long-term immunosuppressive treatment. The aim of the present study was to investigate the effect of different immunosuppressive drugs used in routine clinical practice on Treg and Breg cell numbers. METHODS: Thirty-six kidney transplant recipients with stable graft function were recruited and classified according to their concomitant therapy: 22 patients received calcineurin inhibitors (CNI) and 14 patients received mammalian target of rapamycin (mTOR) inhibitors...
March 2016: Transplant Immunology
https://www.readbyqxmd.com/read/26799240/trends-in-the-use-of-maintenance-immunosuppressive-drugs-among-liver-transplant-recipients-in-taiwan-a-nationwide-population-based-study
#14
Ying-Yu Huang, Chia-Chen Hsu, Chia-Lin Chou, Che-Chuan Loong, Min-Shan Wu, Yueh-Ching Chou
PURPOSE: During the past two decades, many novel immunosuppressive drugs have been approved for transplant recipients. Trends in the use of maintenance immunosuppressants after liver transplantation in Asia are unclear. Thus, we aimed to analyze the prescription trends in maintenance immunosuppressive drugs among liver transplant recipients in Taiwan and compare the results with the trends reported from western countries. METHODS: We conducted a retrospective nationwide population-based study utilizing the National Health Insurance Research Database (NHIRD) to analyze the prescribing patterns of immunosuppressants used in Taiwanese liver transplant recipients from 2000 to 2009...
June 2016: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/26775180/changes-in-lipid-and-carbohydrate-metabolism-under-mtor-and-calcineurin-based-immunosuppressive-regimen-in-adult-patients-after-liver-transplantation
#15
Anca Zimmermann, Christina Zobeley, M M Weber, H Lang, Peter R Galle, Tim Zimmermann
BACKGROUND: Cardiovascular disease is a leading cause of long-term mortality after liver transplantation (LT). Life long immunosuppression harbors the risk of metabolic alterations. We aimed to analyze the impact of calcineurin (CNI)-only containing regimen (group A) compared to mTOR-containing regimen (group B) on lipid and carbohydrate metabolism. PATIENTS/METHODS: 92 adult patients after LT, University of Mainz (group A-78 patients, group B-14 patients; 65 M/27 F; mean age 59+/-10...
April 2016: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/26720300/pubertal-development-in-pediatric-kidney-transplant-patients-receiving-mammalian-target-of-rapamycin-inhibitors-or-conventional-immunosuppression
#16
Julia Förster, Thurid Ahlenstiel-Grunow, Antonia Zapf, Martin Mynarek, Lars Pape
INTRODUCTION: Data regarding the onset of puberty in children receiving mammalian target of rapamycin (mTOR) inhibitors are limited. METHODS: Kidney transplant patients aged <14 years were analyzed retrospectively to a maximum age of 18 years, with a minimal observation period of 1 year. Immunosuppression comprised (1) standard CNI-based regimen or (2) low-exposure mTOR inhibitor with reduced-exposure CNI, initiated either de novo or in the maintenance phase...
December 30, 2015: Transplantation
https://www.readbyqxmd.com/read/26707694/fewer-cytomegalovirus-complications-after-kidney-transplantation-by-de-novo-use-of-mtor-inhibitors-in-comparison-to-mycophenolic-acid
#17
J Radtke, N Dietze, V N Spetzler, L Fischer, E-G Achilles, J Li, S Scheidat, F Thaiss, B Nashan, M Koch
BACKGROUND: Cytomegalovirus (CMV) is a risk factor for patient and graft survival after kidney transplantation. METHODS: We retrospectively analyzed risk factors for CMV infection in 348 patients who received a kidney transplant donated after brain death (n = 232) or by living donation (n = 116) between 2008 and 2013. Of the 348 patients analyzed, 91 received a mammalian target of rapamycin inhibitor (mTORi)-based immunosuppressive regimen. A total of 266 patients were treated with standard immunosuppression (Group 1) consisting of basiliximab induction, calcineurin inhibitor (CNI), and either mycophenolic acid (MPA, n = 219) or everolimus (EVE) (n = 47)...
February 2016: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/26678359/an-mtor-inhibitor-based-protocol-and-calcineurin-inhibitor-cni-free-treatment-in-kidney-transplant-recipients-from-donors-after-cardiac-death-good-renal-function-but-high-incidence-of-conversion-to-cni
#18
Ana Sánchez-Escuredo, Fritz Diekmann, Ignacio Revuelta, Nuria Esforzado, Maria Jose Ricart, Frederic Cofán, Jose-Vicente Torregrosa, Lluis Peri, Ángel Ruiz, Josep Maria Campistol, Federico Oppenheimer
Donor after cardiac death (DCD) grafts have excellent survival despite the high incidence of delayed graft function (DGF). We assessed the feasibility of a mammalian target of rapamycin inhibitor (mTOR-I) protocol in uncontrolled DCD kidney transplantation and compared it with brain-dead donor (DBD) transplantation under calcineurin inhibitor (CNI) treatment. This retrospective study (2002-2011) included 109 Maastricht category II DCD patients and 218 standard-criteria DBD as controls. Immunosuppression consisted of polyclonal antibody induction, mycophenolate mofetil, prednisone, and mTOR-I (starting on day 6) in the DCD group and tacrolimus in the DBD group...
March 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/26667069/safety-of-mtor-inhibitors-in-adult-solid-organ-transplantation
#19
Pedro Ventura-Aguiar, Josep Maria Campistol, Fritz Diekmann
INTRODUCTION: Mammalian target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) are a class of immunosuppressive drugs approved for solid organ transplantation (SOT). By inhibiting the ubiquitous mTOR pathway, they present a peculiar safety profile. The increased incidence of serious adverse events in early studies halted the enthusiasm as a kidney sparing alternative to calcineurin inhibitors (CNI). AREAS COVERED: Herein we review mTOR inhibitors safety profile for adult organ transplantation, ranging from acute side effects, such as lymphoceles, delayed wound healing, or cytopenias, to long-term ones which increase morbidity and mortality, such as cancer risk and metabolic profile...
2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/26608590/long-term-renal-function-in-liver-transplant-recipients-after-conversion-from-calcineurin-inhibitors-to-mtor-inhibitors
#20
COMPARATIVE STUDY
Anna Hüsing, Martina Schmidt, Susanne Beckebaum, Vito R Cicinnati, Raphael Koch, Gerold Thölking, Jaqueline Stella, Hauke Heinzow, Hartmut H Schmidt, Iyad Kabar
BACKGROUND: Renal dysfunction often occurs in liver transplant (LT) recipients receiving calcineurin inhibitor (CNI)-based immunosuppressive regimens, increasing morbidity and mortality rates. Replacement of CNIs by mTOR inhibitor-based immunosuppressive protocols may prevent renal impairment in LT recipients. MATERIAL/METHODS: Outcomes in patients who underwent LT between 1996 and 2010 at our center and who were switched from CNI-based to mTOR inhibitor-based immunosuppression were retrospectively analyzed...
2015: Annals of Transplantation: Quarterly of the Polish Transplantation Society
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