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Calcineurins rejection preservation

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https://www.readbyqxmd.com/read/27742383/immunosuppression-minimization-and-avoidance-protocols-when-less-is-not-more
#1
Rohini Prashar, K K Venkat
Kidney transplantation is well established as the best treatment option for end-stage kidney disease. It confers not only a better quality of life but also a significant survival advantage compared to dialysis. However, despite significant improvement in short-term kidney transplant graft survival over the past three decades, long-term graft survival remains suboptimal. Concerns about the possible contribution of chronic calcineurin inhibitor (CNI) nephrotoxicity to late allograft failure and other serious adverse effects of currently used immunosuppressive agents (especially corticosteroids) have led to increasing interest in developing regimens which may better preserve kidney allograft function and minimize other immunosuppression-related problems without increasing the risk of rejection...
September 2016: Advances in Chronic Kidney Disease
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/27639190/early-conversion-to-prednisolone-everolimus-as-an-alternative-weaning-regimen-associates-with-beneficial-renal-transplant-histology-and-function-the-randomized-controlled-mecano-trial
#3
F J Bemelman, J W de Fijter, J Kers, C Meyer, H Peters-Sengers, E F de Maar, K A M I van der Pant, A P J de Vries, J-S Sanders, A Zwinderman, M M Idu, S Berger, M E J Reinders, C Krikke, I M Bajema, M C van Dijk, I J M Ten Berge, J Ringers, J Lardy, D Roelen, D-J Moes, S Florquin, J J Homan van der Heide
In renal transplantation, use of calcineurin inhibitors (CNIs) is associated with nephrotoxicity and immunosuppression with malignancies and infections. This trial aimed to minimize CNI exposure and total immunosuppression while maintaining efficacy. We performed a randomized controlled, open-label multicenter trial with early cyclosporine A (CsA) elimination. Patients started with basiliximab, prednisolone (P), mycophenolate sodium (MPS), and CsA. At 6 months, immunosuppression was tapered to P/CsA, P/MPS, or P/everolimus (EVL)...
September 17, 2016: American Journal of 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
#4
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/27234735/induction-immunosuppressive-therapy-with-everolimus-and-low-dose-tacrolimus-extended-release-preserves-good-renal-function-at-1%C3%A2-year-after-kidney-transplantation
#5
K Yamanaka, Y Kakuta, S Nakazawa, T Kato, T Abe, R Imamura, M Okumi, N Ichimaru, M Kyo, M Kyakuno, S Takahara, N Nonomura
BACKGROUND: Utilization of everolimus (EVR) has been increasing in recent years for patients undergoing renal transplantation to reduce calcineurin inhibitor (CNI) levels. However, an optimum regimen has yet to be established. METHODS: We retrospectively examined 12 renal transplant recipients who underwent an induction immunosuppressive protocol; the protocol comprises 5 agents, including EVR plus low-dose tacrolimus extended-release (TAC-ER) treatment. We compared those findings from those of 14 patients who underwent a conventional protocol without EVR...
April 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27109983/use-of-everolimus-after-multivisceral-transplantation-a-report-of-two-cases
#6
B Rao, M C Segovia, M Kazimi, R Parekh, M Raoufi, S-M Jafri
Inhibitors of mechanistic target of rapamycin are used in solid organ transplant procedures to avoid calcineurin inhibitor complications, including nephrotoxicity and malignancy. We present 2 cases of multivisceral transplantation for neuroendocrine tumor (NET) for which everolimus was implemented for its potential to prevent NET recurrence as well as preserve renal function. The first case was complicated by NET recurrence in the liver before initiation of everolimus. After initiation of everolimus, the patient developed a ventral hernia and elevated aminotransferase levels with nonspecific biopsy findings...
March 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/26968190/safety-and-immunologic-benefits-of-conversion-to-sirolimus-in-kidney-transplant-recipients-with-long-term-exposure-to-calcineurin-inhibitors
#7
Ji Hyun Yu, Kyoung Woon Kim, Bo-Mi Kim, Byung Ha Chung, Mi-La Cho, Bum Soon Choi, Cheol Whee Park, Yong-Soo Kim, Chul Woo Yang
BACKGROUND/AIMS: Sirolimus (SRL) is a promising immunosuppressant replacingcalcineurin inhibitors (CNIs). This study was performed to evaluate the safetyand immunologic benefits of conversion to SRL in stable kidney transplant (KT)recipients exposed to CNIs for long periods. METHODS: Fourteen CNI-treated KT recipients with stable renal function for morethan 10 years were included. Either 2 or 3 mg per day of SRL was administeredwhile CNIs were reduced by half starting on day 1, and then stopped 2 weeks afterSRL introduction...
May 2016: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/26888217/design-and-rationale-of-the-athena-study-a-12-month-multicentre-prospective-study-evaluating-the-outcomes-of-a-de-novo-everolimus-based-regimen-in-combination-with-reduced-cyclosporine-or-tacrolimus-versus-a-standard-regimen-in-kidney-transplant-patients-study
#8
Claudia Sommerer, Barbara Suwelack, Duska Dragun, Peter Schenker, Ingeborg A Hauser, Björn Nashan, Friedrich Thaiss
BACKGROUND: Immunosuppression with calcineurin inhibitors remains the mainstay of treatment after kidney transplantation; however, long-term use of these drugs may be associated with nephrotoxicity. In this regard, the current approach is to optimise available immunosuppressive regimens to reduce the calcineurin inhibitor dose while protecting renal function without affecting the efficacy. The ATHENA study is designed to evaluate renal function in two regimens: an everolimus and reduced calcineurin inhibitor-based regimen versus a standard treatment protocol with mycophenolic acid and tacrolimus in de novo kidney transplant recipients...
2016: Trials
https://www.readbyqxmd.com/read/26842532/early-initiation-of-everolimus-after-liver-transplantation-a-single-center-experience
#9
Uta Herden, Antonio Galante, Lutz Fischer, Sven Pischke, Jun Li, Eike Achilles, Martina Koch, Bjoern Nashan, Martina Sterneck
BACKGROUND: Evidence relating to early everolimus use after liver transplantation remains limited. MATERIAL AND METHODS: Ninety-one adult patients undergoing liver transplantation at our center during 2007-2012 in whom everolimus therapy was initiated <3 months post-transplant were analyzed retrospectively. Everolimus was started on days 1-5 in 50 patients (group 1) and after day 5 in 41 patients (group 2). Most patients continued to receive low-dose cyclosporine (59...
2016: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/26718625/effect-of-an-early-switch-to-belatacept-among-calcineurin-inhibitor-intolerant-graft-recipients-of-kidneys-from-extended-criteria-donors
#10
Y Le Meur, F Aulagnon, D Bertrand, A E Heng, S Lavaud, S Caillard, H Longuet, R Sberro-Soussan, L Doucet, A Grall, C Legendre
Transplant recipients receiving a kidney from an extended-criteria donor (ECD) are exposed to calcineurin inhibitor (CNI) nephrotoxicity, as demonstrated by severe delayed graft function and/or a low GFR. Belatacept is a nonnephrotoxic drug that is indicated as an alternative to CNIs. We reported 25 cases of conversion from a CNI to belatacept due to CNI intolerance within the first 6 mo after transplantation. The mean age of the recipients was 59 years, and 24 of 25 patients received ECD kidneys. At the date of the medication switch, 12 of 25 patients displayed a calculated GFR (cGFR) <15 mL/min, six patients remained on dialysis, and the biopsies showed evidence of acute tubular damage associated with severe vascular or tubulointerstitial chronic lesions...
July 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/26364728/a-retrospective-comparison-of-mycophenolate-mofetil-with-low-exposure-cyclosporine-versus-standard-cyclosporine-therapy-in-de-novo-liver-transplant-patients
#11
COMPARATIVE STUDY
Jonas D Senft, Daniel N Gotthardt, Lina Frischbier, Helge Bruns, Peter Schemmer
BACKGROUND Data on low-exposure calcineurin inhibitor therapy with mycophenolate mofetil (MMF) in de novo liver transplant patients are limited and restricted to tacrolimus. MATERIAL AND METHODS Twenty-eight patients receiving cyclosporine and MMF at a single center were identified retrospectively and categorized as low-exposure or standard-exposure CsA (median concentration <80 ng/mL [n=16] or ≥80 ng/mL [n=12] during days 1-7) and analyzed to 12 weeks post-transplant. RESULTS Biopsy-proven acute rejection (Banff ≥4) occurred in 3 low-CsA patients and no standard-CsA patients (p=0...
September 12, 2015: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/26293038/evolution-of-renal-function-in-renal-allograft-recipients-under-various-everolimus-based-immunosuppressive-regimens
#12
C Skalioti, S Marinaki, M Darema, S Lionaki, N Antonakopoulos, G Zavos, J Boletis
BACKGROUND: Long-term allograft survival is a major challenge in kidney transplantation. This study sought to estimate the evolution of renal function in patients receiving different immunosuppressive regimens based on everolimus (EVR). METHODS: Ninety-nine renal allograft recipients were included in a 12-month open-label, noninterventional, prospective, single-center study. Patients were divided into 2 groups, de novo and late conversion to EVR. RESULTS: Group A included 40 patients under calcineurin inhibitor (CNI) plus EVR...
July 2015: Transplantation Proceedings
https://www.readbyqxmd.com/read/25513193/fibrosis-progression-in-maintenance-liver-transplant-patients-with-hepatitis-c-recurrence-a-randomised-study-of-everolimus-vs-calcineurin-inhibitors
#13
Federico G Villamil, Adrian C Gadano, Fernanda Zingale, Roberto Perez, Octavio Gil, Silvina Yantorno, Ricardo Mastai, Fernando O Cairo, Alcira B Otero, Gaohong Dong, Patricia Lopez
BACKGROUND & AIMS: Robust clinical data evaluating fibrosis progression in hepatitis C virus (HCV) liver transplant patients receiving an mTOR inhibitor vs. calcineurin inhibitor (CNI) are lacking. To evaluate fibrosis progression in maintenance liver transplant patients receiving everolimus- or CNI-based immunosuppression. METHODS: In a randomised, multicentre, open-label study, 43 maintenance liver transplant patients with recurrent HCV infection were randomised to continue CNI-based immunosuppression or switch to everolimus...
November 2014: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/25512099/renal-efficacy-and-safety-outcomes-following-late-conversion-of-kidney-transplant-patients-from-calcineurin-inhibitor-therapy-to-everolimus-the-randomized-apollo-study
#14
RANDOMIZED CONTROLLED TRIAL
Klemens Budde, Thomas Rath, Claudia Sommerer, Hermann Haller, Petra Reinke, Oliver Witzke, Barbara Suwelack, Daniel Baeumer, Christoph May, Martina Porstner, Wolfgang Arns
AIMS: The primary objective of this trial was to demonstrate, based on the estimated glomerular filtration rate (eGFR), superior renal function at month 12 after conversion of maintenance kidney transplant patients from calcineurin inhibitor (CNI) therapy to everolimus, compared to continuing a standard CNI regimen. MATERIALS AND METHODS: APOLLO was an open-label, 12-month, prospective, multicenter study in which 93 maintenance kidney transplant patients were randomized to convert from CNI to everolimus (n = 46) or remain on standard CNI-based immunosuppression (n = 47)...
January 2015: Clinical Nephrology
https://www.readbyqxmd.com/read/25453134/fibrosis-progression-in-maintenance-liver-transplant-patients-with-hepatitis-c-recurrence-a-randomised-study-of-everolimus-vs-calcineurin-inhibitors
#15
RANDOMIZED CONTROLLED TRIAL
Federico G Villamil, Adrian C Gadano, Fernanda Zingale, Roberto Perez, Octavio Gil, Silvina Yantorno, Ricardo Mastai, Fernando O Cairo, Alcira B Otero, Gaohong Dong, Patricia Lopez
BACKGROUND & AIMS: Robust clinical data evaluating fibrosis progression in hepatitis C virus (HCV) liver transplant patients receiving an mTOR inhibitor vs. calcineurin inhibitor (CNI) are lacking. To evaluate fibrosis progression in maintenance liver transplant patients receiving everolimus- or CNI-based immunosuppression. METHODS: In a randomised, multicentre, open-label study, 43 maintenance liver transplant patients with recurrent HCV infection were randomised to continue CNI-based immunosuppression or switch to everolimus...
November 2014: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/24983307/safety-and-efficacy-of-the-early-introduction-of-everolimus-with-reduced-exposure-cyclosporine-a-in-de-novo-kidney-recipients
#16
RANDOMIZED CONTROLLED TRIAL
Chang-Kwon Oh, Kyu Ha Huh, Jongwon Ha, Yeong Hoon Kim, Yong-Lim Kim, Yu Seun Kim
BACKGROUND: Everolimus and cyclosporine A (CsA) exhibit synergistic immunosuppressive activity when used in combination. We examined the safety and efficacy of the use of everolimus with a cyclosporine-sparing strategy in de novo renal transplant recipients. METHODS: A comparative, parallel, randomized, open-label 1-year study has been performed in 148 patients from five transplant centers to compare the efficacy and tolerability of everolimus and reduced exposure CsA (the investigational group) or enteric-coated mycophenolate sodium and standard-exposure CsA (the control group) in combination with basiliximab and steroids...
January 2015: Transplantation
https://www.readbyqxmd.com/read/24738962/renal-function-preservation-with-the-mtor-inhibitor-everolimus-after-lung-transplant
#17
Sonia Schneer, Mordechai R Kramer, Benjamin Fox, Viktoria Rusanov, Oren Fruchter, Dror Rosengarten, Ilana Bakal, Benjamin Medalion, Yael Raviv
Chronic kidney disease (CKD) is a common complication of calcineurin inhibitors (CNIs) in solid organ transplantation. Previous data suggest that the use of everolimus as an immunosuppressant drug leads to improvement in renal function. The aim of our study was to establish the effect of everolimus in combination with lower doses of CNIs on renal function among lung transplant recipients. Data regarding renal function and pulmonary function were collected from 41 lung transplanted patients in whom treatment was converted to a combination of everolimus with lower doses of CNIs...
June 2014: Clinical Transplantation
https://www.readbyqxmd.com/read/24620724/co-stimulatory-blockade-with-belatacept-in-kidney-transplantation
#18
REVIEW
Bhavna Chopra, Kalathil K Sureshkumar
Calcineurin inhibitors (CNIs) are the cornerstone of immunosuppression after transplantation but can exert negative effects on chronic allograft function and metabolic profile. Belatacept, a selective co-stimulation blocker of T cells, is the first biologic agent approved for maintenance immunosuppression in kidney transplantation. Studies reveal better preservation of glomerular filtration rate and improved metabolic end points with belatacept when compared to CNIs. Increased incidence of acute rejection is noted with belatacept but overall graft survival looked similar at 5 years...
May 2014: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/24565406/jak3-inhibition-what-potential-for-the-future
#19
Christophe Legendre
JAK3 inhibition with the CP-690,550 compound has an immunosuppressive potency in murine models, nonhuman primates and humans. This drug blocks STAT5 activation in most T-cell subpopulations but less effectively in T-regulator cells. In low to moderate risk human kidney transplant recipients, combined with mycophenolate mofetil, steroids and an induction with basiliximab, CP-690,550 proved as effective as calcineurin inhibitors with regard to prevention of acute rejection but better than calcineurin inhibitors with regard to preservation of kidney function and histology...
November 20, 2013: Transplantation Research
https://www.readbyqxmd.com/read/24502384/everolimus-and-early-calcineurin-inhibitor-withdrawal-3-year-results-from-a-randomized-trial-in-liver-transplantation
#20
RANDOMIZED CONTROLLED TRIAL
M Sterneck, G M Kaiser, N Heyne, N Richter, F Rauchfuss, A Pascher, P Schemmer, L Fischer, C G Klein, S Nadalin, F Lehner, U Settmacher, P Neuhaus, D Gotthardt, M Loss, S Ladenburger, E M Paulus, M Mertens, H J Schlitt
The feasibility of de novo everolimus without calcineurin inhibitor (CNI) therapy following liver transplantation was assessed in a multicenter, prospective, open-label trial. Liver transplant patients were randomized at 4 weeks to start everolimus and discontinue CNI, or continue their current CNI-based regimen. The primary endpoint was adjusted estimated GFR (eGFR; Cockcroft-Gault) at month 11 post randomization. A 24-month extension phase followed 81/114 (71.1%) of eligible patients to month 35 post randomization...
March 2014: American Journal of Transplantation
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