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tacrolimus and sirolimus

Yingzi Ming, George B Stefano, Richard M Kream, Quan Zhuang
Widespread usage of the calcineurin inhibitors tacrolimus and cyclosporine A as post-transplantation immunosuppressive agents is fraught with severe nephrotoxic and diabetogenic side effects. More recently, tapering of calcineurin inhibitor-based immunotherapies with concurrent administration of the mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus has been employed within pharmacological regimens designed to achieve better safety and efficacy for preservation of allograft kidney function...
February 10, 2019: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Diğdem Özer Etik, Nuretdin Suna, Serkan Öcal, Haldun Selçuk, Ülkü Dağlı, Turan Çolak, Fatih Hilmioğlu, Ahmet Sedat Boyacıoğlu, Mehmet Haberal
OBJECTIVES: The introduction of direct-acting antiviral agents has allowed significant chances for treatment for difficult-to-treat populations. This study aimed to investigate the efficacy, tolerability, and safety of these therapies in both patients with end-stage renal disease and kidney transplant recipients with chronic hepatitis C virus infection. MATERIALS AND METHODS: This study was a retrospective analysis with prospective follow-up of patients. The antiviral combination of ombitasvir 25 mg, paritaprevir 75 mg, ritonavir 50 mg, and dasabuvir 50 mg was prescribed to patients with end-stage renal disease or kidney transplant recipients with noncirrhotic or compensated cirrhotic liver disease...
February 2019: Experimental and Clinical Transplantation
Richard J Hendrickson, Joseph Sujka, Ryan Fischer, Michelle Manalang, James Daniel, Walter S Andrews
SRL-based immunosuppressive strategies in pediatric liver transplantation are not clearly defined, especially within the first year after liver transplant. TAC is the more common, traditional immunosuppressant used. However, SRL may modulate TAC-associated kidney injury and may also have antiproliferative properties that are valuable in the management of patients following liver transplantation for HB. We sought to determine whether early conversion from TAC to SRL was safe, effective, and beneficial in a subset of liver transplant recipients with unresectable HB exposed to CDDP-based chemotherapy...
February 4, 2019: Pediatric Transplantation
Johan Törlén, Ahmed Gaballa, Mats Remberger, Lisa-Mari Mörk, Berit Sundberg, Jonas Mattsson, Michael Uhlin
Lymphocyte reconstitution is pivotal for successful long-term outcome after allogeneic hematopoietic stem cell transplantation (HSCT), and conditioning and post-transplant immunosuppression constitute risk factors for prolonged immunodeficiency. Nevertheless, the effect of different immunosuppressive protocols on lymphocyte output and replicative capacity has not been investigated. Here, we assessed T-cell receptor excision circles (TREC), kappa-deleting recombination excision circles (KREC), and T-cell telomere length (TL) as proxy markers for immune reconstitution in patients in a prospective randomized trial comparing graft-versus-host disease (GVHD) prophylaxis after transplantation (cyclosporine/methotrexate vs...
January 30, 2019: Biology of Blood and Marrow Transplantation
Yasbanoo Moayedi, Carlos A Gomez, Chun Po S Fan, Robert J H Miller, Paul E Bunce, Maxime Tremblay-Gravel, Farid Foroutan, Cedric Manlhiot, James Yee, Michael A Shullo, Kiran K Khush, Heather J Ross, Jose G Montoya, Jeffrey J Teuteberg
BACKGROUND: The risk of infection after heart transplantation is highest within the first year and represents the leading cause of early mortality. In this cohort of patients enrolled in the Outcomes AlloMap Registry (OAR), we sought to describe infection episodes (IEp) resulting in hospitalization, in the early (<1 year) and late (≥1 year) post-transplant period and determine the impact of immunosuppression on incidence of infection. METHODS: The primary aim was to assess the incidence and nature of IEp...
January 7, 2019: Journal of Heart and Lung Transplantation
Christer Holmberg
PURPOSE OF REVIEW: Nonadherence is a problem in adolescents and young adults. Risk factors are classified as those of the individual, family, health-care-system, or community. I present the latest reports and how to tackle nonadherence. RECENT FINDINGS: Nonadherence risk is independent of one's origin in a high-poverty or low-poverty neighborhood or having private or public insurance in respect to African Americans. Females with male grafts have higher graft-failure risks than do males...
January 21, 2019: Current Opinion in Pediatrics
Beatriz Guglieri-Lopez, Alejandro Perez-Pitarch, Irene Garcia-Cadenas, Estela Gimenez, Pere Barba, Nuria Rabella, Juan Carlos Hernandez-Boluda, Laura Fox, David Valcarcel, Albert Esquirol, Rafael Ferriols-Lisart, Jorge Sierra, Carlos Solano, David Navarro, Rodrigo Martino, José Luis Piñana
The current study evaluates the clinical effect of sirolimus exposure on the occurrence of cytomegalovirus (CMV) DNAemia necessitating preemptive antiviral therapy. A total of 167 consecutive recipients of reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT) who received sirolimus- and tacrolimus-based graft-versus-host disease (GVHD) prophylaxis and whose CMV serostatus was positive for donors and/or recipients were included in this multicenter retrospective study...
January 10, 2019: Biology of Blood and Marrow Transplantation
Shulian Tan, Liangsong Song, Meifang Wang, Wenjie Zhao, Yongguang Yang
OBJECTIVE: Diabetes is a common chronic disease. ARF is a new tumor suppressor, which is one hotspot of cell cycle regulators. The mutation of ARF is absent in nearly 50% of tumors. ARF plays an important role in many physiological processes, such as cell proliferation, cell senescence and cell cycle arrest. However, the molecular mechanism of ARF regulating is not clear at present. Our study aims to explore the mechanism of ARF in diabetes. METHODS: ARF-Tg mice and C57 mice were fasted for 12 hours before the experiment...
January 2, 2019: Artificial Cells, Nanomedicine, and Biotechnology
Saeideh Jamali, Abdolfatah Sarafnejad, Pedram Ahmadpoor, Mohsen Nafar, Mozhdeh Karimi, Atefeh Eteghadi, Mir Saeed Yekaninejad, Ali Akbar Amirzargar
BACKGROUND: Accumulating evidence suggests that regulatory T cells (Tregs) have a crucial role in immune tolerance and long-term graft survival. However, the influence of immunosuppressive drugs on the level of Tregs has not been fully understood. Therefore we prospectively compare the effect of two different calcineurin inhibitor (CNI)-based immunosuppression protocols on Tregs frequencies and expression of regulatory and effector T cell-related genes in renal transplant recipients. METHODS: The study included 24 renal transplant recipients who received induction therapy (Antithymocyte globulin) and were on triple immunosuppressive therapy so that one group was on Tacrolimus (Tac), mycophenolate moftile (MMF) and prednisolone (P) whereas another group was on Tac, Sirolimus (SRL) and P...
December 28, 2018: Human Immunology
Rong Wang, Xuan Sun, Yong-Shu Deng, Xu-Wen Qiu
1. Overexpression of P-glycoprotein (P-gp, encoded by MDR1) mediates resistance to multiple immunosuppressors. Several common MDR1 variants (1236C > T, 2677G > T, 3435C > T) impact the efflux activity of P-gp- mediated substrates. We assessed the effect of these polymorphisms on the sensitivity, intracellular accumulation, and efflux of tacrolimus, cyclosporine A, sirolimus, and everolimus in transfected LLC-PK1 cells. 2. LLC-PK1 cell lines were transfected with empty vector (pcDNA3.1) and recombinant MDR1T-T-T , MDR1C-T-T , MDR1C-G-T , and MDR1C-G-C vectors, respectively and further screened in the presence of puromycin...
December 27, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
L Gao, F Xu, H Cheng, J Liu
PURPOSE: The study was designed to compare the outcomes of sirolimus (SRL) combined with tacrolimus (TAC) and mycophenolate mofetil (MMF) combined with TAC in kidney transplantation recipients. METHODS: A literature search of PubMed, Embase, and Web of Science was performed to identify relevant studies, and the last update was on February 1, 2018. All studies with appropriate data comparing the SRL group with the MMF group were included. SRL and MMF were used in sufficient doses...
December 2018: Transplantation Proceedings
Atefeh Eteghadi, Fatemeh Pak, Pedram Ahmadpoor, Saeideh Jamali, Mozhdeh Karimi, Mir Saeed Yekaninejad, Parviz Kokhaei, Mohsen Nafar, Ali Akbar Amirzargar
Long-term use of calcineurin inhibitors (CNI) is associated with nephrotoxicity, which is an important cause of renal dysfunction. Therefore, CNI-minimization strategies which decrease the CNI nephrotoxicity under the protection of additional immunosuppressant drugs have been developed. The aim of current cohort study was to compare the effect of two immunosuppressive protocols [tacrolimus (TAC) in combination with mycophenolate mofetil (MMF) and prednisolone (PRED) versus TAC in combination with sirolimus (SRL) and prednisolone] on the frequency of T helper cell subsets (Th1, Th2 and Th17 cells) and their associated cytokine (IFN-γ, IL-4 and IL-17A) levels in renal allograft recipients...
December 17, 2018: International Immunopharmacology
Ahmed F Hamdy, Muhammed A Elhadedy, Ahmed F Donia, Noheir M Taha, Mohamed A Bakr
In a prospective randomized controlled trial, between May 2001 and January 2003, 132 live donor kidney transplant recipients were randomized to receive sirolimus primary immunosuppression, either in combination with low dose tacrolimus (TAC group) or in combination with mycophenolate mofetil (MMF group). We have previously reported on two and five year- follow up results, with favorable patient and graft outcomes obtained in both groups. In view of recent published reports of increased risk of inferior outcomes among sirolimus- treated patients, we herein present results of an observational extension of the previously randomized patients 15 years post -transplantation...
December 13, 2018: Clinical Transplantation
Helio Tedesco-Silva, Maria Del Carmen Rial, Jose Cruz Santiago, Marilda Mazzali, Alvaro Pacheco-Silva, Rodolfo Torres
While calcineurin inhibitors (CNIs) are effective for preventing acute rejection in kidney transplant recipients, long-term use may cause chronic kidney injury and is associated with increased risks of cardiovascular events, cancer, and infection-associated death. Immunosuppression strategies are needed to balance risks of acute and subclinical rejection with long-term benefits of improved kidney function. Sirolimus, an inhibitor of mammalian target of rapamycin, is used for immunosuppression in kidney transplantation...
December 13, 2018: Clinical Transplantation
Andre L Silva, Daniéliso R Fusco, Hong S Nga, Henrique M Takase, Ariane M Bravin, Mariana M Contti, Mariana F Valiatti, Luis Gustavo M de Andrade
Background: In animal models, the mammalian target of rapamycin inhibitors (mTORIs) may prevent atherogenesis by the regulation of homeostasis of cholesterol and by a reduced inflammatory response. The aim of this study is to compare the carotid intima-media thickness (cIMT) between de novo tacrolimus/mycophenolate and tacrolimus/sirolimus at low doses. The cIMT is considered a surrogate marker of atherosclerosis. Methods: We evaluated cIMT at baseline and at 6 and 12 months after kidney transplantation in a database derived from a previously published trial...
December 2018: Clinical Kidney Journal
Venkat Bhat, Mahmood Tazari, Kymberly D Watt, Mamatha Bhat
OBJECTIVE: To identify key predictors and survival outcomes of new-onset diabetes after transplant (NODAT) in liver transplant (LT) recipients by using the Scientific Registry of Transplant Recipients. PATIENTS AND METHODS: Data of all adult LT recipients between October 1, 1987, and March 31, 2016, were analyzed using various machine learning methods. These data were divided into training (70%) and validation (30%) data sets to robustly determine predictors of NODAT...
December 2018: Mayo Clinic Proceedings
Sebastian C B Bremer, Lars Reinhardt, Michael Sobotta, Marie C Hasselluhn, Thomas Lorf, Volker Ellenrieder, Harald Schwörer
Background: Liver transplant recipients are frequently treated with proton pump inhibitors. Drug interactions have been described especially with respect to omeprazole. Due to the lower binding capacity of pantoprazole to CYP2C19 this drug became preferred and became the most used proton pump inhibitor in Germany. The data on the influence of pantoprazole on immunosuppressive drugs in liver transplant recipients a very scarce. Methods: The authors performed a single center analysis in liver transplant recipients on the effect of pantoprazole on the serum trough levels of different immunosuppressants...
2018: Frontiers in Medicine
Kai-Fan Tsai, Lung-Chih Li, Chien-Ning Hsu, Chih-Che Lin, Yu-Hung Lin, Yu-Fan Cheng, Chih-Chi Wang, Chao-Long Chen
Mammalian targets of rapamycin inhibitors (mTORIs), including sirolimus and everolimus, are used for minimizing calcineurin inhibitors after liver transplantation. However, head-to-head randomized comparisons of these 2 mTORIs are lacking. We assessed the differences in renoprotection and possible mechanisms between sirolimus and everolimus in liver transplant recipients. For this prospective cohort study, we recruited liver transplant recipients whose regimens were switched from tacrolimus to sirolimus or everolimus at a Taiwan medical center...
November 2, 2018: Journal of Clinical Pharmacology
Noruel Gerard A Salvador, Sin-Yong Wee, Chih-Che Lin, Chao-Chien Wu, Hung-I Lu, Ting-Lung Lin, Wei-Feng Lee, Yi-Chia Chan, Li-Man Lin, Chao-Long Chen
BACKGROUND This study aimed to determine clinical outcomes using various drugs during tuberculosis (TB) treatment among living donor liver transplant (LDLT) recipients with TB and to assess the impact of performing LDLT in patients with active TB at the time of LDLT. MATERIAL AND METHODS Out of 1313 LDLT performed from June 1994 to May 2016, 26 (2%) adult patients diagnosed with active TB were included in this study. Active TB was diagnosed using either TB culture, PCR, and/or tissue biopsy. RESULTS The median age was 56 years and the male/female ratio was 1...
October 19, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Shuhui Si, Zijie Wang, Haiwei Yang, Zhijian Han, Jun Tao, Hao Chen, Ke Wang, Miao Guo, Ruoyun Tan, Ji-Fu Wei, Min Gu
The P450 oxidoreductase (POR) and peroxisome proliferator-activated receptor alpha (PPARA) genes are associated with the activity of cytochrome P450 enzymes in vivo. We aimed to investigate the impact of single nucleotide polymorphisms (SNPs) in the POR and PPARA genes on the pharmacokinetics of tacrolimus (TAC) in renal transplant recipients. A total of 220 recipients were assessed and 105 recipients were included for final quantitative analysis. Blood samples were collected and DNA was extracted. Targeting sequencing based on next-generation sequencing was applied to detect the SNPs in the POR and PPARA genes...
October 15, 2018: Pharmacogenomics Journal
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