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Everolimus renal transplantation

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https://www.readbyqxmd.com/read/29779413/tailoring-tacrolimus-therapy-in-kidney-transplantation
#1
Thomas Jouve, Johan Noble, Lionel Rostaing, Paolo Malvezzi
BACKGROUND: The prevalence of end-stage renal disease is increasing worldwide. The best treatment is kidney transplantation, although life-long immunosuppressive therapy is then mandatory. Currently, the cornerstone immunosuppressive therapy relies on tacrolimus, a calcineurin inhibitor that is nephrotoxic but whose exposition can be minimized in a delicate balance. Area covered: We addressed whether, in the setting of kidney transplantation, tacrolimus-based therapy can be tailored to medical needs: to achieve this, we searched for suitable articles in PubMed...
May 19, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29771270/effect-of-conversion-from-calcineurin-inhibitors-to-everolimus-on-hepatitis-c-viremia-in-adult-kidney-transplant-recipients
#2
Larissa Sgaria Pacheco, Valter Duro Garcia, Ronivan Luis Dal Prá, Bruna Doleys Cardoso, Mariana Ferras Rodrigues, Helen Kris Zanetti, Gisele Meinerz, Jorge Neumann, Diego Gnatta, Elizete Keitel
INTRODUCTION: Currently, there is no specific immunosuppressive protocol for hepatitis C (HCV)-positive renal transplants recipients. Thus, the aim of this study was to evaluate the conversion effect to everolimus (EVR) on HCV in adult kidney recipients. METHOD: This is an exploratory single-center, prospective, randomized, open label controlled trial with renal allograft recipients with HCV-positive serology. Participants were randomized for conversion to EVR or maintenance of calcineurin inhibitors...
May 14, 2018: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/29769264/rhoa-g17v-is-sufficient-to-induce-autoimmunity-and-promotes-t-cell-lymphomagenesis-in-mice
#3
Samuel Y Ng, Leon Brown, Kristen Stevenson, Tiffany deSouza, Jon C Aster, Abner Louissaint, David M Weinstock
Patients with angioimmunoblastic T-cell lymphoma (AITL) and other peripheral T-cell lymphomas (PTCL) that harbor features of follicular helper T (TFH) cells have a very poor prognosis. These lymphomas commonly present with paraneoplastic autoimmunity and lymphopenia. RhoA G17V mutation is present in 60% of TFH-like lymphomas but its role in tumorigenesis is poorly understood. We generated transgenic mice that express RhoA G17V under the control of murine CD4 regulatory elements at levels comparable to a heterozygous mutation (tgRhoA mice)...
May 16, 2018: Blood
https://www.readbyqxmd.com/read/29757021/advagraf%C3%A2-with-or-without-an-induction-therapy-for-de-novo-kidney-transplant-recipients
#4
Johan Noble, Thomas Jouve, Lionel Rostaing, Paolo Malvezzi
Cornerstone immunosuppressive therapy currently relies on immediate-release tacrolimus, a calcineurin inhibitor (CNI) that is potentially nephrotoxic and is more diabetogenic than cyclosporine A. Two new formulations of tacrolimus have been launched: an extended-release formulation (Advagraf®/Astagraf XL®, Astellas company) and a long-lasting formulation (Envarsus®, Veloxis company). Area covered: Herein, we assess the efficacy of an extended-release formulation of tacrolimus (Advagraf®/Astagraf XL®) used in conjunction with or without an induction therapy (i...
May 14, 2018: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/29752413/everolimus-with-reduced-calcineurin-inhibitor-exposure-in-renal-transplantation
#5
Julio Pascual, Stefan P Berger, Oliver Witzke, Helio Tedesco, Shamkant Mulgaonkar, Yasir Qazi, Steven Chadban, Federico Oppenheimer, Claudia Sommerer, Rainer Oberbauer, Yoshihiko Watarai, Christophe Legendre, Franco Citterio, Mitchell Henry, Titte R Srinivas, Wen-Lin Luo, AnaMaria Marti, Peter Bernhardt, Flavio Vincenti
Background Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation. Methods In a multicenter noninferiority trial, we randomized 2037 de novo kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR<50 ml/min per 1...
May 11, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29722128/five-year-outcomes-in-kidney-transplant-patients-randomized-to-everolimus-with-cyclosporine-withdrawal-or-low-exposure-cyclosporine-versus-standard-therapy
#6
Claudia Sommerer, Michael Duerr, Oliver Witzke, Frank Lehner, Wolfgang Arns, Volker Kliem, Daniel Ackermann, Markus Guba, Johannes Jacobi, Ingeborg A Hauser, Rolf Stahl, Petra Reinke, Thomas Rath, Justyna Veit, Arianeb Mehrabi, Martina Porstner, Klemens Budde
HERAKLES was a one-year randomized, multicenter trial. Patients were randomized at three months after kidney transplantation to remain on cyclosporine-based therapy, switch to everolimus without a calcineurin inhibitor (CNI), or switch to everolimus with low-exposure cyclosporine. Overall, 417/497 (83.9%) patients from the core study entered a four-year extension study. The randomized regimen was continued to year 5 in 75.9%, 41.9% and 24.6% of patients in the standard-CNI, CNI-free and low-CNI groups, respectively...
May 2, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29705974/extreme-hypercalcemia-in-a-kidney-transplant-recipient
#7
Erol Demir, Cagla Karaoglan, Gulcin Yegen, Betul Sair, Halil Yazici, Aydin Turkmen, Mehmet Sukru Sever
Post-transplant hypercalcemia is a major problem in renal transplant recipients, which may negatively affect both graft and patient survival. In this paper, we present a 66-year-old male kidney transplant recipient, who was admitted to our clinic with symptoms of fever, nausea, vomiting and lethargy. Laboratory data showed good renal function; however, a serum calcium level of 22.1 mg/dL. The patient was treated by isotonic saline together with furosemide and methylprednisolone. Because of treatment resistance, subcutaneous calcitonin and ibandronate were added to the treatment protocol as well...
April 28, 2018: CEN Case Reports
https://www.readbyqxmd.com/read/29684618/everolimus-is-a-new-anti-cancer-molecule-metabolic-side-effects-as-lipid-disorders-and-hyperglycemia
#8
REVIEW
L Morviducci, F Rota, L Rizza, P Di Giacinto, S Ramponi, M R Nardone, C Tubili, A Lenzi, P Zuppi, R Baldelli
In the last few years, molecular targeted therapies have replaced traditional cytotoxic chemotherapy in the fight against many cancers to the extent that our understanding of tumor biology has become more sophisticated. This shift has markedly changed adverse event profiles, compared to cytotoxic chemotherapy, affecting a diverse range of organ systems. Everolimus was approved by the FDA in 2011 for the treatment of progressive pancreatic NE tumors (Yao, 2011; Jensenn, 2012). It is an inhibitor of mammalian target of rapamycin (mTOR) and exhibits antitumor activity via disruption of various signaling pathways and it's used in the treatment of advanced renal cell cancer, breast cancer and neuroendocrine tumors (NET); it's used also as anti-rejection agent for transplantation but with lower doses for anti-rejection (1...
April 20, 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29679515/the-influence-of-mtor-inhibitors-on-the-incidence-of-cmv-infection-in-high-risk-donor-positive-recipient-negative-d-r-kidney-transplant-recipients
#9
M P Cristelli, R M Esmeraldo, C Motta Pinto, T V Sandes-Freitas, C Felipe, C F Lobo, L Viana, J Mansur, S Stopa, D W C Santos, P C Grenzi, W F Aguiar, H Tedesco-Silva, J O Medina-Pestana
Several studies and meta-analysis suggest the mTOR inhibitors are associated with reduced incidence of CMV infection after kidney transplantation, although their effects on the high-risk population have not been investigated thoroughly. This retrospective cohort study investigates the association between immunosuppression and CMV infection in D+/R- kidney transplant recipients receiving preemptive therapy. All patients received rabbit anti-thymocyte globulin, tacrolimus, prednisone and azathioprine (AZA), mycophenolate (MPA) or everolimus (EVR)...
April 21, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/29679392/comparison-of-electrochemiluminescence-immunoassay-and-latex-agglutination-turbidimetric-immunoassay-for-evaluation-of-everolimus-blood-concentrations-in-renal-transplant-patients
#10
Y Akamine, S Sato, H Kagaya, T Ohkubo, S Satoh, M Miura
WHAT IS KNOWN AND OBJECTIVE: For analysis of blood concentrations of everolimus, many hospital laboratories use either latex agglutination turbidimetric immunoassay (LTIA) or electrochemiluminescence immunoassay (ECLIA). However, no studies have compared both immunoassay methods under the same conditions. Accordingly, in this study, we compared everolimus blood concentrations obtained by LTIA and ECLIA in renal transplant patients. METHODS: Blood samples (n = 230) from 60 renal transplant patients (19 female and 41 male) were evaluated using both immunoassays...
April 20, 2018: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29661455/management-of-juvenile-idiopathic-arthritis-in-abo-incompatible-kidney-transplantation-a-case-report
#11
S Ishikawa, M Tasaki, T Kuroda, D Kobayashi, K Saito, Y Nakagawa, M Ikeda, K Takahashi, Y Tomita
Biologic agents are a beneficial therapy for juvenile idiopathic arthritis (JIA). However, there is a lack of evidence with regard to management of these agents for JIA patients who undergo kidney transplantation (KTx). A 36-year-old woman with JIA who was treated with tocilizumab targeting interleukin-6 (IL-6) receptor underwent ABO-incompatible kidney transplantation (ABOi KTx). To prevent over-immunosuppression, tocilizumab was discontinued before ABOi KTx. Rituximab, tacrolimus, mycophenolate mofetil, everolimus, and methylprednisolone were used for immunosuppression...
April 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29588066/life-threatening-everolimus-associated-pneumonitis-a-case-report-and-a-review-of-the-literature
#12
F Almeida, S Amorim, A Sarmento, L Santos
INTRODUCTION: Noninfective pneumonitis is a class-related effect within mammalian target of rapamycin (mTOR) inhibitors, including everolimus, and can occasionally be severe. CASE REPORT: A 62-year-old man, medicated with everolimus due to a heart transplantation 17 years previously and with chronic kidney disease, was admitted to the intensive care unit (ICU) with acute respiratory failure, cardiovascular shock, and impaired renal function requiring dialysis. Computed tomography (CT) scan revealed right upper lobe consolidation...
March 24, 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29571743/acute-inflammatory-syndrome-paradoxically-induced-by-de-novo-purine-inhibitors-synthesis-before-renal-transplantation-a-case-report-and-review-of-the-literature
#13
Y Maruyama, T Sadahira, Y Mitsui, K Wada, R Tanimoto, S Nishimura, Y Kobayashi, T Watanabe, Y Nasu, M Araki
BACKGROUND: Mycophenolate mofetil (MMF) and mizoribine (MZR) are increasingly used as immunosuppressive agents for organ transplantation and chronic inflammation. We report a patient with rheumatoid arthritis who had an acute inflammatory syndrome triggered by preoperative immunosuppression therapy with both MMF and MZR. CASE REPORT: A 41-year-old woman with IgA nephropathy was referred to our department for living donor renal transplantation. She had rheumatoid arthritis that was adequately treated with prednisolone 5 mg once a day and salazosulfapyridine 2000 mg once a day...
March 21, 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29556934/a-limited-sampling-strategy-to-estimate-exposure-of-everolimus-in-whole-blood-and-peripheral-blood-mononuclear-cells-in-renal-transplant-recipients-using-population-pharmacokinetic-modeling-and-bayesian-estimators
#14
Ida Robertsen, Jean Debord, Anders Åsberg, Pierre Marquet, Jean-Baptiste Woillard
BACKGROUND AND OBJECTIVE: Intracellular exposure of everolimus may be a better marker of therapeutic effect than trough whole blood concentrations. We aimed to develop pharmacokinetic population models and Bayesian estimators based on a limited sampling strategy for estimation of dose interval exposures of everolimus in whole blood and peripheral blood mononuclear cells (PBMCs) in renal transplant recipients. METHODS: Full whole blood and PBMC concentration-time profiles of everolimus were obtained from 12 stable renal transplant recipients on two different occasions, 4 weeks apart...
March 20, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29547545/prediction-of-tacrolimus-exposure-by-cyp3a5-genotype-and-exposure-of-co-administered-everolimus-in-japanese-renal-transplant-recipients
#15
Hideaki Kagaya, Takenori Niioka, Mitsuru Saito, Takamitsu Inoue, Kazuyuki Numakura, Ryohei Yamamoto, Yumiko Akamine, Tomonori Habuchi, Shigeru Satoh, Masatomo Miura
While tacrolimus and everolimus have common metabolic pathways through CYP3A4/5, tacrolimus is metabolized solely by CYP3A4 in recipients with the CYP3A5*3 / *3 . The purpose of this study was to evaluate how the area under the blood concentration-time curves (AUC) of tacrolimus could be predicted based on CYP3A5 genotype and the AUC of everolimus in renal transplant patients taking both drugs. The dose-adjusted AUC (AUC/D) of tacrolimus and everolimus were calculated at one month and one year after transplantation...
March 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29407305/ab-initio-everolimus-based-versus-standard-calcineurin-inhibitor-immunosuppression-regimen-in-liver-transplant-recipients
#16
T M Manzia, R Angelico, L Toti, C Grimaldi, D Sforza, I Vella, L Tariciotti, I Lenci, G Breshanaj, L Baiocchi, G Tisone
AIM: We designed a retrospective case-control study to determine the efficacy and feasibility of everolimus (EVR) combined with low-dose tacrolimus (Tac) ab initio versus standard-dose Tac after liver transplantation (LT). METHODS: Seventy-one adult LT patients, receiving EVR and low-dose Tac without corticosteroids or induction therapy from postoperative day 1 (EVR group) were compared with a well-matched control group of 61 recipients treated with standard-dose Tac in association with antimetabolite...
January 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29369972/mtor-inhibition-and-kidney-diseases
#17
Maggie K M Ma, Susan Yung, Tak Mao Chan
Mammalian or mechanistic target of rapamycin (mTOR) is a serine-threonine kinase that plays essential roles in cell growth, proliferation, metabolism, and survival. Increased activation of the mTOR pathway is observed in patients and animal models of renal transplant rejection, autosomal dominant polycystic kidney disease, renal cell carcinoma, diabetic nephropathy, lupus nephritis, and angiomyolipoma. Agents that inhibit mTOR, such as sirolimus and everolimus, are incorporated in immunosuppressive regimens to prevent renal allograft rejection and are often used to facilitate calcineurin inhibitor minimization or to reduce the incidence of tumor recurrence...
February 2018: Transplantation
https://www.readbyqxmd.com/read/29237235/efficacy-and-safety-of-everolimus-with-reduced-tacrolimus-in-living-donor-liver-transplant-recipients-12-month-results-of-a-randomized-multicenter-study
#18
Long-Bin Jeng, Sung Gyu Lee, Arvinder Singh Soin, Wei-Chen Lee, Kyung-Suk Suh, Dong Jin Joo, Shinji Uemoto, Jaewon Joh, Tomoharu Yoshizumi, Horng-Ren Yang, Gi-Won Song, Patricia Lopez, Jossy Kochuparampil, Carole Sips, Shuhei Kaneko, Gary Levy
In a multicenter, open-label, study, 284 living-donor liver transplant patients were randomized at 30 ± 5 days posttransplant to start everolimus+reduced tacrolimus (EVR+rTAC) or continue standard tacrolimus (TAC Control). EVR+rTAC was non-inferior to TAC Control for the primary efficacy endpoint of treated BPAR, graft loss or death at 12 months posttransplant: difference -0.7% (90% CI -5.2%, 3.7%); P < .001 for non-inferiority. Treated BPAR occurred in 2.2% and 3.6% of patients, respectively. The key secondary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, achieved non-inferiority (P < ...
December 13, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29151264/renal-protection-strategies-after-heart-transplantation
#19
REVIEW
Daniel Reichart, Hermann Reichenspurner, Markus Johannes Barten
Renal dysfunction caused by calcineurin inhibitor (CNI) nephrotoxicity occurs often and contributes significantly to late mortality after heart transplantation (HTx). Over the last decades, this has prompted many clinical studies in an effort to develop kidney-protecting immunosuppressive strategies including delayed CNI start, minimization, withdrawal, or even de novo CNI avoidance. In the past, these strategies often failed due to the lack of efficacy. Since 2009, novel CNI-reducing strategies have been under investigation...
January 2018: Clinical Transplantation
https://www.readbyqxmd.com/read/29075123/immunosuppressants-and-new-onset-gallstone-disease-in-patients-having-undergone-renal-transplantation
#20
Fu-Chao Liu, Pei-Chi Ting, Jr-Rung Lin, Huang-Ping Yu
BACKGROUND: There are very few reports describing the development of gallstone disease after renal transplantation (GSDART) in Asia. The aim of this population-based study was to explore the prevalence, predictive factors, and outcomes of newly developed GSDART. The relationship between immunosuppressant and GSDART was also explored. PATIENTS AND METHODS: Renal transplantation (RT) recipients were identified from the National Health Insurance Research Database of Taiwan during January 1998-December 2012...
2017: Therapeutics and Clinical Risk Management
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