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sirolimus to tacrolimus

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https://www.readbyqxmd.com/read/27888534/early-steroid-withdrawal-results-in-improved-patient-and-graft-survival-and-lower-risk-of-post-transplant-cardiovascular-risk-profiles-a-single-center-10-year-experience
#1
Reynold Lopez-Soler, Ryan Chan, Jessica Martinolich, Lisa Park, Ashar Ata, Nikolaos Chandolias, David Conti
Long term use of steroids results in predictable secondary effects that can lead to increased morbidity and mortality. In this study, we present 10 years' worth of data of early steroid withdrawal (ESW) immunosuppression consisting of Mycophenolate, Sirolimus, and Tacrolimus. From 2003 to 2013, 563 kidney transplant recipients were weaned off steroids prior to discharge. We compared outcomes with that of our 65 historical controls maintained on steroids. We analyzed graft and patient survival and determined the incidence of steroid-related comorbidities such as hypertension, hypercholesterolemia, diabetes, coronary artery disease, and weight gain...
November 26, 2016: Clinical Transplantation
https://www.readbyqxmd.com/read/27819684/tacrolimus-plus-sirolimus-with-or-without-atg-as-gvhd-prophylaxis-in-hla-mismatched-unrelated-donor-allogeneic-stem-cell-transplantation
#2
M A Kharfan-Dabaja, R Parody, J Perkins, O Lopez-Godino, L Lopez-Corral, L Vazquez, D Caballero, J Falantes, J Shapiro, G Ortí, P Barba, D Valcárcel, A Esquirol, R Martino, J L Piñana, C Solano, A Tsalatsanis, J Pidala, C Anasetti, J A Perez-Simón
HLA-matched related or unrelated donors are not universally available. Consequently, patients can be offered hematopoietic stem cell transplantation (HSCT) from alternative donors, including mismatched unrelated donors (MMURD), known to cause a higher incidence of acute GVHD (aGVHD) and chronic GVHD. In vivo T-cell-depletion strategies, such as antithymocyte globulin (ATG) therapy, significantly decrease the risk of GVHD. We performed a multicenter, retrospective study comparing tacrolimus (TAC) and sirolimus (SIR) with or without ATG in 104 patients (TAC-SIR=45, TAC-SIR-ATG=59) who underwent MMURD HSCT...
November 7, 2016: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27795990/early-kidney-allograft-dysfunction-threatened-allograft-comparative-effectiveness-of-continuing-versus-discontinuation-of-tacrolimus-and-use-of-sirolimus-to-prevent-graft-failure-a-retrospective-patient-centered-outcome-study
#3
Ravinder K Wali, Heather A Prentice, Venkata Reddivari, Geroge Baffoe-Bonnie, Cinthia I Drachenberg, John C Pappadimitriou, Emilio Ramos, Matthew Cooper, Johann Jonsson, Stephen Bartlett, Matthew R Weir
BACKGROUND: Due to lack of treatment options for early acute allograft dysfunction in the presence of tubular-interstitial injury without histological features of rejection, kidney transplant recipients are often treated with sirolimus-based therapy to prevent cumulative calcineurin inhibitor exposure and to prevent premature graft failure. METHODS: We analyzed transplant recipients treated with sirolimus-based (n = 220) compared with continued tacrolimus-based (n = 276) immunosuppression in recipients of early-onset graft dysfunction (threatened allograft) with the use of propensity score-based inverse probability treatment weighted models to balance for potential confounding by indication between 2 nonrandomized groups...
September 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27795987/outcomes-of-pancreatic-islet-allotransplantation-using-the-edmonton-protocol-at-the-university-of-chicago
#4
Zehra Tekin, Marc R Garfinkel, W James Chon, Lindsay Schenck, Karolina Golab, Omid Savari, J Richard Thistlethwaite, Louis H Philipson, Colleen Majewski, Silvana Pannain, Sabarinathan Ramachandran, Kourosh Rezania, Seenu M Hariprasad, J Michael Millis, Piotr Witkowski
OBJECTIVE: The aim of this study was to assess short-term and long-term results of the pancreatic islet transplantation using the Edmonton protocol at the University of Chicago. MATERIALS AND METHODS: Nine patients underwent pancreatic islet cell transplantation using the Edmonton Protocol; they were followed up for 10 years after initial islet transplant with up to 3 separate islet infusions. They were given induction treatment using an IL-2R antibody and their maintenance immunosuppression regimen consisted of sirolimus and tacrolimus...
October 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27754567/adhere-randomized-controlled-trial-comparing-renal-function-in-de-novo-kidney-transplant-recipients-receiving-prolonged-release-tacrolimus-plus-mmf-or-sirolimus
#5
Oleg O Rummo, Mario Carmellini, Lionel Rostaing, Rainer Oberbauer, Maarten H L Christiaans, Christiane Mousson, Robert M Langer, Franco Citterio, Bernard Charpentier, Malcolm Brown, Gbenga Kazeem, Frank Lehner
ADHERE was a randomized, open-label, Phase IV study comparing renal function at Week 52 post-kidney transplant, in patients who received prolonged-release tacrolimus-based immunosuppressive regimens. On days 0-27, patients received prolonged-release tacrolimus (initially 0.2mg/kg/day), corticosteroids and mycophenolate mofetil (MMF). Patients were randomized on Day 28 to receive either prolonged-release tacrolimus plus MMF (Arm 1) or prolonged-release tacrolimus (≥25% dose-reduction on Day 42) plus sirolimus (Arm 2)...
October 18, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27754526/-current-status-and-regulation-of-bioanalytical-laboratories-engaged-in-quantifying-immunosuppressants-for-transplant-patients-in-argentina
#6
Paula Schaiquevich, Paula Taich, Natalia Riva, Francisco Leone, Nora Paternoster, Gabriel Mato, Paulo Cáceres Guido
Objective Determine the status of analytical laboratories that quantify immunosuppressants in transplant patients who are under therapeutic drug monitoring (TDM) for these drugs in Argentina in order to identify potential perfectible areas for action. Methods A survey of the clinical and analytical TDM centers in Argentina was conducted between September 2013 and November 2014 under the direction of the Garrahan Hospital Clinical Pharmacokinetics Unit and the National Unified Central Institute for Ablation and Implant Coordination...
March 2016: Revista Panamericana de Salud Pública, Pan American Journal of Public Health
https://www.readbyqxmd.com/read/27748705/the-impact-of-total-gastrectomy-on-pharmacokinetics-in-kidney-transplant-immunosuppressive-drug-regimes-a-case-study
#7
Lucy Chen, Lisa Liberatore, Tom Chin, Scott Walker, Helen Fanous, Michelle M Nash, Lindita Rapi, Jennie Huckle, Jeffrey S Zaltzman, G V Ramesh Prasad
BACKGROUND: Ensuring reliable gastrointestinal drug absorption of orally-administered immunosuppressive medications posttransplant is critical to ensuring graft survival. METHODS: A 66 year old man of East Asian origin with a previous total gastrectomy was evaluated for living donor kidney transplantation. Pretransplant pharmacokinetic testing was performed to determine the most appropriate posttransplant medication strategy. The Gastrointestinal Quality of Life Index and Gastrointestinal Rating Scale questionnaires were administered to gauge immunosuppressive medication-related side effects in the absence of a stomach...
September 29, 2016: Transplantation
https://www.readbyqxmd.com/read/27688296/effects-of-metformin-on-hyperglycemia-in-an-experimental-model-of-tacrolimus-and-sirolimusinduced-diabetic-rats
#8
Jian Jin, Sun Woo Lim, Long Jin, Ji Hyun Yu, Hyun Seon Kim, Byung Ha Chung, Chul Woo Yang
Background/Aims: Metformin (MET) is a first-line drug for type 2 diabetes mellitus (DM); its effect on new-onset diabetes after transplantation caused by immunosuppressant therapy is unclear. We compared the effects of MET on DM caused by tacrolimus (TAC) or sirolimus (SRL). Methods: DM was induced by injection of TAC (1.5 mg/kg) or SRL (0.3 mg/kg) for 2 weeks in rats, and MET (200 mg/kg) was injected for 2 more weeks. The effects of MET on DM caused by TAC or SRL were evaluated using an intraperitoneal glucose tolerance test (IPGTT) and by measuring plasma insulin concentration, islet size, and glucose-stimulated insulin secretion (GSIS)...
September 30, 2016: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/27662016/a-prospective-randomized-trial-comparing-cyclosporine-methotrexate-and-tacrolimus-sirolimus-as-graft-versus-host-disease-prophylaxis-after-allogeneic-hematopoietic-stem-cell-transplantation
#9
Johan Törlén, Olle Ringdén, Karin Garming-Legert, Per Ljungman, Jacek Winiarski, Kari Remes, Maija Itälä-Remes, Mats Remberger, Jonas Mattsson
Improvement of graft-versus-host disease prophylaxis remains an important goal in allogeneic hematopoietic stem cell transplantation. Based on reports of possibly preferential properties of sirolimus, we compared the standard regimen of cyclosporine and methotrexate (n=106) with a combination of tacrolimus and sirolimus (n=103) as graft-versus host disease prophylaxis after allogeneic hematopoietic stem cell transplantation in a prospective, open, randomized trial. The hypothesis was that the tacrolimus/sirolimus regimen would lead to less acute graft-versus-host disease and reduced transplant-related mortality...
August 4, 2016: Haematologica
https://www.readbyqxmd.com/read/27564782/differential-risks-for-adverse-outcomes-3-years-after-kidney-transplantation-based-on-initial-immunosuppression-regimen-a-national-study
#10
Vikas R Dharnidharka, Mark A Schnitzler, Jiajing Chen, Daniel C Brennan, David Axelrod, Dorry L Segev, Kenneth B Schechtman, Jie Zheng, Krista L Lentine
We examined integrated national transplant registry, pharmacy fill, and medical claims data for Medicare-insured kidney transplant recipients in 2000-2011 (n = 45 164) from the United States Renal Data System to assess the efficacy and safety endpoints associated with seven early (first 90 days) immunosuppression (ISx) regimens. Risks of clinical complications over 3 years according to IS regimens were assessed with multivariate regression analysis, including the adjustment for covariates and propensity for receipt of a nonreference ISx regimen...
November 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27518575/differential-antitumoral-properties-and-renal-associated-tissue-damage-induced-by-tacrolimus-and-mammalian-target-of-rapamycin-inhibitors-in-hepatocarcinoma-in-vitro-and-in-vivo-studies
#11
Elena Navarro-Villarán, José Tinoco, Granada Jiménez, Sheila Pereira, Jize Wang, Sara Aliseda, María A Rodríguez-Hernández, Raúl González, Luís M Marín-Gómez, Miguel A Gómez-Bravo, Francisco J Padillo, José M Álamo-Martínez, Jordi Muntané
Orthotopic liver transplantation (OLT) is the recommended treatment for patients at early stages of hepatocarcinoma (HCC) with potential portal hypertension and/or bilirubinemia, but without vascular-associated diseases. The patients are receiving immunosuppressive therapy to reduce graft rejection, but differential side effects have been related to calcineurin and mTOR inhibitor administration regarding tumor recurrence and nephrotoxicity. The in vitro studies showed that Tacrolimus exerted a more potent pro-apoptotic effect than Everolimus (Huh 7>Hep 3B>HepG2), being sirolimus only active in Hep3B cell line...
2016: PloS One
https://www.readbyqxmd.com/read/27500260/open-label-randomized-study-of-transition-from-tacrolimus-to-sirolimus-immunosuppression-in-renal-allograft-recipients
#12
Helio Tedesco-Silva, V Ram Peddi, Ana Sánchez-Fructuoso, Brad A Marder, Graeme R Russ, Fritz Diekmann, Alison Flynn, Carolyn M Hahn, Huihua Li, Michael A Tortorici, Seth L Schulman
UNLABELLED: Calcineurin inhibitor-associated nephrotoxicity and other adverse events have prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney transplant recipients. METHODS: This open-label, randomized, multinational study evaluated the effect of planned transition from tacrolimus to sirolimus on kidney function in renal allograft recipients. Patients received tacrolimus-based immunosuppression and then were randomized 3 to 5 months posttransplantation to transition to sirolimus or continue tacrolimus...
April 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27478685/effects-of-molecularly-targeted-therapies-on-murine-thymus-highly-selective-mtor-inhibitors-induce-reversible-thymic-involution
#13
Suleiman Al-Hammadi, Saeeda Almarzooqi, Alia Albawardi, Abdul-Kader Souid
BACKGROUND: Blocking mTOR (molecular target of rapamycin) by sirolimus has been shown to suppress cellular respiration. The bearing of this impaired cellular bioenergetics on the mode-of-action of mTOR inhibitors has yet to be illustrated. METHODS: This study investigated in vitro effects of several molecularly-targeted therapies on O2 consumption in thymic fragments from C57BL/6 mice. RESULTS: Thymocyte respiration (µM O2 min(-1) mg(-1)) was reduced by sirolimus and everolimus (p ≤ 0...
2015: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/27372284/experiences-from-using-lc-ms-ms-for-analysis-of-immunosuppressive-drugs-in-a-tdm-service
#14
Anton Pohanka, Staffan Rosenborg, Jonatan D Lindh, Olof Beck
A liquid chromatography-tandem mass spectrometry method is presented that was applied for over five years for routine measurement of the immunosuppressant drugs ciclosporin, everolimus, sirolimus and tacrolimus in blood. The method has been used for analysis of 142 thousand unknowns and has been running 7days a week without a single day shutdown during the entire time. The measuring ranges were 10-1500ng/mL for ciclosporin and 1-50ng/mL for everolimus, sirolimus and tacrolimus. The method validation showed performance meeting the EMA validation guideline requirements and acceptable performance in a proficiency control program...
September 2016: Clinical Biochemistry
https://www.readbyqxmd.com/read/27344165/differential-influence-of-tacrolimus-and-sirolimus-on-mitochondrial-dependent-signaling-for-apoptosis-in-pancreatic-cells
#15
Andrei Alexandru Constantinescu, Malak Abbas, Mohamad Kassem, Céline Gleizes, Guillaume Kreutter, Valerie Schini-Kerth, Ioan Liviu Mitrea, Florence Toti, Laurence Kessler
To examine and compare the mitochondria-related cellular mechanisms by which tacrolimus (TAC) or sirolimus (SIR) immunosuppressive drugs alter the pancreatic exocrine and endocrine β-cell fate. Human exocrine PANC-1 and rat endocrine insulin-secreting RIN-m5F cells and isolated rat islets were submitted to 1-100 nM TAC or SIR. In cultures, insulin secretion was measured as endocrine cell function marker. Apoptosis was quantified by annexin 5 and propidium iodide staining. Cleaved caspase-3, Bax apoptosis indicators, and p53, p21 cell cycle regulators were detected by Western blot...
July 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27310200/risk-assessment-of-drug-drug-interactions-of-calcineurin-inhibitors-affecting-sirolimus-pharmacokinetics-in-renal-transplant-patients
#16
Chie Emoto, Alexander A Vinks, Tsuyoshi Fukuda
BACKGROUND: Sirolimus is a mammalian target of rapamycin inhibitor that is being used to prevent organ rejection in kidney transplant patients often in combination with calcineurin inhibitors (CNIs; cyclosporine and tacrolimus). All 3 drugs are metabolized primarily by CYP3As. Clinical drug-drug interaction (DDI) studies of cyclosporine on sirolimus pharmacokinetics have been reported; however, there are a few clinical DDI data related to tacrolimus. METHODS: In vitro inhibition assay with sirolimus were conducted using recombinant CYP3As and human microsomes in the presence and absence of CNIs...
October 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/27293553/reviewing-15%C3%A2-years-of-experience-with-sirolimus
#17
REVIEW
Helio Tedesco Silva, Claudia Rosso Felipe, Jose Osmar Medina Pestana
Here, we review 15 years of clinical use of sirolimus in our transplant center, in context with the developing immunosuppressive strategies use worldwide. The majority of studies were conducted in de novo kidney transplant recipients, using sirolimus (SRL) in combination with calcineurin inhibitors (CNIs). We also explored steroid (ST) or CNI-sparing therapies, including CNI minimization, elimination, or conversion strategies in combination with mycophenolate (MMF/MPS). Pooled long-term outcomes were comparable with those obtained with CNI and antimetabolite combination...
2015: Transplantation Research
https://www.readbyqxmd.com/read/27275747/immunoregulatory-effects-of-everolimus-on-in-vitro-alloimmune-responses
#18
Josh Levitsky, Joshua Miller, Xuemei Huang, Lorenzo Gallon, Joseph R Leventhal, James M Mathew
Everolimus (EVL) is a novel mTOR-inhibitor similar to sirolimus (SRL) that is used in organ transplant recipients, often in combination with tacrolimus (TAC) or mycophenolate (MPA). The current study aims to determine its effects on regulatory T cells. Increasing concentrations of EVL, MPA and TAC alone or in combination were added to MLRs of healthy volunteers. Lymphoproliferation by 3H-TdR incorporation and the percentage of newly generated CD4+CD127-CD25+FOXP3+ (total Treg) and CD4+CD127-CD25HighFOXP3+ (natural Treg) in CFSE labeled responder cells were assessed by flow cytometry...
2016: PloS One
https://www.readbyqxmd.com/read/27210056/pain-syndrome-and-ventricular-arrhythmia-induced-by-sirolimus-and-resolved-by-dosage-adjustment-in-a-child-after-heart-transplant-a-case-report
#19
Nazmi Mutlu Karakas, Ilkay Erdogan, Beril Ozdemir, Atilla Sezgin
For patients with late congenital heart diseases and advanced heart failure, heart transplant is the one of the most effective known treatment methods. With the development of immunosuppressive medicines, it is possible to prevent and treat rejection, and survival after organ transplant has increased rapidly. Calcineurin inhibitors (tacrolimus and cyclosporine), mycophenolate mofetil, and corticosteroids are used together in many centers as immunosuppressive medications. Although the use of calcineurin inhibitors is essential, therapy is switched to sirolimus in some specific cases and when significant adverse effects occur...
May 17, 2016: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/27194037/a-systematic-approach-to-assess-the-burden-of-drug-interactions-in-adult-kidney-transplant-patients
#20
Fernando Bril, Veronica Castro, Ignacio G Centurion, Jeronimo Espinosa, Guillermo A Keller, Claudio D Gonzalez, Maria C Soler Riera, Cristian L Saubidet, Guillermo Di Girolamo, Gervasio S Pujol, Paulino A Alvarez
AIM: Renal transplant patients are frequently subject to polypharmacy and drug-drug interactions. However, no previous study has systematically assessed the risk of drug interactions and Adverse Drug Reactions (ADRs) in this population. METHODS: A total of 138 consecutive adult kidney transplant recipients admitted to our hospital between August 2010 and February 2012 were prospectively and systematically assessed by our pharmacovigilance team, within 24 hours of admission, to identify potential drug-drug interactions and probable ADRs...
2016: Current Drug Safety
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