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Calcineurins rejection preservation

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https://www.readbyqxmd.com/read/29605470/outcomes-associated-with-mammalian-target-of-rapamycin-mtor-inhibitors-in-heart-transplant-recipients-a-meta-analysis
#1
Douglas L Jennings, Nicholas Lange, Michael Shullo, Farhana Latif, Susan Restaino, Veli K Topkara, Koji Takeda, Hiroo Takayama, Yoshifumi Naka, Maryjane Farr, Paolo Colombo, William L Baker
BACKGROUND: Data evaluating mTOR inhibitor use heart transplant (HT) patients comes from relatively small studies and controversy exists regarding their specific role. We performed a meta-analysis of randomized trials to evaluate the efficacy and safety of mTOR inhibitors in HT patients. METHODS: We performed a systematic literature search of Medline and Embase through July 2017 identifying studies evaluating mTOR inhibitors in HT patients reporting effects on coronary allograft vasculopathy (CAV), renal function, acute cellular rejection (ACR), cytomegalovirus (CMV) infection, and discontinuation due to adverse drug events (ADE)...
March 24, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29594146/early-conversion-from-tacrolimus-to-belatacept-in-a-highly-sensitized-renal-allograft-recipient-with-calcineurin-inhibitor-induced-de-novo-post-transplant-hemolytic-uremic-syndrome
#2
Vasishta S Tatapudi, Bonnie E Lonze, Ming Wu, Robert A Montgomery
Background: Kidney transplantation is the first-line therapy for patients with end-stage renal disease since it offers greater long-term survival and improved quality of life when compared to dialysis. The advent of calcineurin inhibitor (CNI)-based maintenance immunosuppression has led to a clinically significant decline in the rate of acute rejection and better short-term graft survival rates. However, these gains have not translated into improvement in long-term graft survival. CNI-related nephrotoxicity and metabolic side effects are thought to be partly responsible for this...
January 2018: Case Reports in Nephrology and Dialysis
https://www.readbyqxmd.com/read/29110799/acute-postoperative-management-after-lung-transplantation
#3
REVIEW
Christopher Potestio, Desmond Jordan, Bessie Kachulis
Despite many advances in the field of lung transplantation, lung transplant recipients have the lowest median survival of any solid organ transplant population. Complications such as reperfusion injury, graft rejection, infection, and anastomotic breakdown increase morbidity and mortality during the immediate postoperative period. Ventilator management with lung protective strategies can not only minimize ventilator time and mitigate the risk of ventilator-associated pneumonia, but it may also decrease the risk of primary graft dysfunction and graft failure...
June 2017: Best Practice & Research. Clinical Anaesthesiology
https://www.readbyqxmd.com/read/28525959/challenges-and-opportunities-in-targeting-the-cd28-ctla-4-pathway-in-transplantation-and-autoimmunity
#4
REVIEW
Rebecca L Crepeau, Mandy L Ford
T cell activation is a complex process that requires multiple cell signaling pathways, including a primary recognition signal and additional costimulatory signals. One of the best-characterized costimulatory pathways includes the Ig superfamily members CD28 and CTLA-4 and their ligands CD80 and CD86. Areas covered: This review discusses past, current and future biological therapies that have been utilized to block the CD28/CTLA-4 cosignaling pathway in the settings of autoimmunity and transplantation, as well the challenges facing successful implementation of these therapies...
August 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28463861/everolimus-immunosuppression-for-renal-protection-reduction-of-allograft-vasculopathy-and-prevention-of-allograft-rejection-in-de-novo-heart-transplant-recipients-could-we-have-it-all
#5
REVIEW
Einar Gude, Lars Gullestad, Arne K Andreassen
PURPOSE OF REVIEW: De-novo introduction of everolimus (Eve) in heart transplant recipients opens for early reduction of calcineurin inhibitors (CNI) and potential of preserving renal function, attenuate progression of coronary allograft vasculopathy (CAV) and maintain rejection efficacy. RECENT FINDINGS: The first trials demonstrated adequate rejection prophylaxis and favorable outcomes on CAV, but observed enhanced nephrotoxicity because of insufficient CNI reduction...
June 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28316600/methylation-of-foxp3-tsdr-underlies-the-impaired-suppressive-function-of-tregs-from-long-term-belatacept-treated-kidney-transplant-patients
#6
Evelyn Katy Alvarez Salazar, Arimelek Cortés-Hernández, Germán Rodrigo Alemán-Muench, Josefina Alberú, Jesús R Rodríguez-Aguilera, Félix Recillas-Targa, Victoria Chagoya de Sánchez, Eric Cuevas, Eduardo Mancilla-Urrea, María Pérez García, Guillermo Mondragón-Ramírez, Mario Vilatobá, Ian Bostock, Erick Hernández-Méndez, David De Rungs, Eduardo A García-Zepeda, Gloria Soldevila
Regulatory T cells (Tregs) are considered key players in the prevention of allograft rejection in transplanted patients. Belatacept (BLT) is an effective alternative to calcineurin inhibitors that appears to preserve graft survival and function; however, the impact of this drug in the homeostasis of Tregs in transplanted patients remains controversial. Here, we analyzed the phenotype, function, and the epigenetic status of the Treg-specific demethylated region (TSDR) in FOXP3 of circulating Tregs from long-term kidney transplant patients under BLT or Cyclosporine A treatment...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28119255/limitations-of-current-liver-transplant-immunosuppressive-regimens-renal-considerations
#7
REVIEW
Wei Zhang, John Fung
BACKGROUND: The use of calcineurin inhibitor (CNI)-based immunosuppressive regimens following liver transplantation (LTx) has improved the outcomes of the recipients. However, CNI has nephrotoxicity and causes short- and long-term renal complications. The progressive structural changes can be irreversible in the long-term, leading to chronic kidney dysfunction. The present review was to evaluate the different strategies of CNI application to renal function in liver recipients. DATA SOURCES: PubMed database was searched for relevant articles in English on the issue of immunosuppressive regimen and kidney injury that related to early minimization of CNI after LTx...
February 2017: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/27966241/clinical-analysis-of-hyperkalemic-renal-tubular-acidosis-caused-by-calcineurin-inhibitors-in-solid-organ-transplant-recipients
#8
W Lin, L Mou, H Tu, L Zhu, J Wang, J Chen, Y Hu
WHAT IS KNOWN AND OBJECTIVE: Calcineurin inhibitor (CNI)-based immunosuppressive regimen is widely used for preventing rejection in solid organ transplantation. Hyperkalemic renal tubular acidosis (RTA) caused by CNI is uncommon and potentially underappreciated. We reported four such cases to increase awareness of this risk and to provide recommendations for its management based on our experience. CASE SUMMARY: Four middle-aged males underwent solid organ transplant (two kidneys, one liver, one heart) and were treated with CNI-based immunosuppressive regimen (one cyclosporine A, three tacrolimus)...
February 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/27941433/kidney-fibrosis-origins-and-interventions
#9
REVIEW
Thomas Vanhove, Roel Goldschmeding, Dirk Kuypers
All causes of renal allograft injury, when severe and/or sustained, can result in chronic histological damage of which interstitial fibrosis and tubular atrophy are dominant features. Unless a specific disease process can be identified, what drives interstitial fibrosis and tubular atrophy progression in individual patients is often unclear. In general, clinicopathological factors known to predict and drive allograft fibrosis include graft quality, inflammation (whether "nonspecific" or related to a specific diagnosis), infections, such as polyomavirus-associated nephropathy, calcineurin inhibitors (CNI), and genetic factors...
April 2017: Transplantation
https://www.readbyqxmd.com/read/27742383/immunosuppression-minimization-and-avoidance-protocols-when-less-is-not-more
#10
REVIEW
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
#11
REVIEW
Gabriel Fernandes-Silva, Mayara Ivani de Paula, Érika B Rangel
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. We summarize the nephrotoxic and diabetogenic mechanisms of mTORi after pancreas transplant, the alternatives to minimize these effects, and report on other adverse events...
April 2017: 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
#12
RANDOMIZED CONTROLLED TRIAL
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)...
April 2017: 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
#13
COMPARATIVE STUDY
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
#14
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
#15
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
#16
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
#17
RANDOMIZED CONTROLLED TRIAL
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...
February 17, 2016: Trials
https://www.readbyqxmd.com/read/26842532/early-initiation-of-everolimus-after-liver-transplantation-a-single-center-experience
#18
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...
February 4, 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
#19
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
#20
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
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