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timing of initiation of calcineurin inhibitors

Thomas Vanhove, Isabel Spriet, Pieter Annaert, Johan Maertens, Johan Van Cleemput, Robin Vos, Dirk Kuypers
BACKGROUND: Calcineurin inhibitors (CNIs) and direct oral anticoagulants (DOACs) share certain metabolic pathways, but whether DOACs influence CNI exposure has not been assessed. METHODS: A single-center retrospective analysis was performed including 39 organ recipients treated with the combination of a CNI and rivaroxaban (n = 29) or apixaban (n = 10). Dose-corrected CNI trough concentrations (C0/D) during 200 days before and after DOAC initiation were recorded (n = 261), together with covariates known to influence CNI disposition such as steroid dose and hematocrit...
November 17, 2016: Therapeutic Drug Monitoring
C M Cruz, S Pereira, J Gandara, S Ferreira, V Lopes, J Daniel, H P Miranda
Calcineurin inhibitors (CNI) are the base of immunosuppressive regimens in liver transplantation but they are associated with significant side effects, namely nephrotoxicity, which leads to increased morbidity and mortality. Through time, mycophenolate mofetil (MMF) as monotherapy has been suggested as an alternative in patients with CNI-related toxicity, but still no consensus has been reached as to its efficacy. We have evaluated the safety, efficacy, and tolerability of MMF monotherapy in selected patients, developing CNI-associated events, focusing primarily on kidney dysfunction...
September 2016: Transplantation Proceedings
Markus J Barten, Uwe Schulz, Andres Beiras-Fernandez, Michael Berchtold-Herz, Udo Boeken, Jens Garbade, Stephan Hirt, Manfred Richter, Arjang Ruhpawar, Jan Dieter Schmitto, Felix Schönrath, Rene Schramm, Martin Schweiger, Markus Wilhelm, Andreas Zuckermann
There is currently no consensus regarding the dose or duration of rabbit antithymocyte globulin (rATG) induction in different types of heart transplant patients, or the timing and intensity of initial calcineurin inhibitor (CNI) therapy in rATG-treated individuals. Based on limited data and personal experience, the authors propose an approach to rATG dosing and initial CNI administration. Usually rATG is initiated immediately after exclusion of primary graft failure, although intraoperative initiation may be appropriate in specific cases...
June 2016: Transplantation Direct
J Malyszko, R Kowalewski, J Glowinski, J Malyszko, E Koc-Zorawska, I Glowinska, U Lebkowska, M Gacko
BACKGROUND: Hepcidin is a peptide hormone that regulates iron homeostasis. Hepcidin may represent an early, predictive biomarker of acute kidney injury, another model of ischemia-reperfusion injury. Urinary hepcidin-25 has been shown to be elevated in patients who do not develop acute kidney injury. Creatinine is an unreliable indicator during acute changes in kidney; therefore, the aim of the study was to assess whether hepcidin could predict renal outcome in 31 consecutive patients undergoing kidney allograft transplantation...
June 2016: Transplantation Proceedings
Paolo De Simone, Stefano Fagiuoli, Matteo Cescon, Luciano De Carlis, Giuseppe Tisone, Riccardo Volpes, Umberto Cillo
Immunosuppression after liver transplantation (LT) is presently based on use of calcineurin inhibitors (CNI), although they are associated with an increased incidence of renal dysfunction, cardiovascular complications, and de novo and recurrent malignancies. Over the past decade, mammalian target of rapamycin inhibitors have received considerable attention as immunosuppressants because they are associated with a more favorable renal profile versus CNI, as well as antiproliferative activity in clinical studies...
2017: Transplantation
Kiran Mirza, Finn Gustafsson, Lars Gullestad, Satish Arora, Claus Andersen
BACKGROUND: Through immunosuppression CD4+FoxP3+ regulatory T-cells (Tregs) play an indispensable role in allograft rejection. Post-HTx treatment with everolimus is associated with slower progression of cardiac allograft vasculopathy (CAV) - chronic rejection - than CNI based therapy. We hypothesized treatment with everolimus reduced the risk of CAV by modulating myocardial FoxP3 levels. METHODS: 15 patients from the Schedule trial comparing everolimus, MMF, steroid and early CNI (Everolimus, n=8) withdrawal to conventional CNI based immunosuppression (Controls, n=7) after de novo HTx were included and FoxP3+ cells were quantified in 56 endomyocardial biopsies, and compared in the two patient groups...
September 2016: Transplant Immunology
Clement Wilfred Devadass, Aruna Vishwanth Vanikar, Lovelesh Kumar Nigam, Kamal Vinod Kanodia, Rashmi Dalsukhbhai Patel, Kyasakkala Sannaboraiah Vinay, Himanshu V Patel
INTRODUCTION: Biopsy remains gold standard for diagnosis of Graft Dysfunction (GD). It guides clinical management, provides valuable insights into pathogenesis of early and late allograft injury and is indispensable for distinguishing rejection from non- rejection causes of GD. AIM: The primary aim of the study was to evaluate the diverse histomorphological lesions in renal allograft biopsy (RAB). Further, we determined the frequency of peritubular capillary (PTC) C4d positivity and its correlation with microvascular inflammation in Antibody Mediated Rejection (AMR)...
March 2016: Journal of Clinical and Diagnostic Research: JCDR
Gerold Thölking, Lea Siats, Christian Fortmann, Raphael Koch, Anna Hüsing, Vito R Cicinnati, Hans Ulrich Gerth, Heiner H Wolters, Christoph Anthoni, Hermann Pavenstädt, Barbara Suwelack, Hartmut H Schmidt, Iyad Kabar
BACKGROUND: The calcineurin inhibitor (CNI) tacrolimus (Tac) is an effective immunosuppressant used after liver transplantation (LTx), but is often associated with CNI nephrotoxicity. Currently, there is no simple clinical predictor for CNI nephrotoxicity after LTx. We hypothesized that the Tac metabolism rate - defined as the blood concentration normalized by its daily dose (the C/D ratio) - is associated with post-LTx renal impairment. MATERIAL AND METHODS: We analyzed the relationship between the C/D ratio and post-transplant renal function in 179 patients who underwent LTx between 2000 and 2012 and were initially immunosuppressed with Tac, mycophenolate mofetil, and prednisolone...
March 22, 2016: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Louis-Philippe Laurin, Adil M Gasim, Caroline J Poulton, Susan L Hogan, J Charles Jennette, Ronald J Falk, Bethany J Foster, Patrick H Nachman
BACKGROUND AND OBJECTIVES: In primary FSGS, calcineurin inhibitors have primarily been studied in patients deemed resistant to glucocorticoid therapy. Few data are available about their use early in the treatment of FSGS. We sought to estimate the association between choice of therapy and ESRD in primary FSGS. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used an inception cohort of patients diagnosed with primary FSGS by kidney biopsy between 1980 and 2012...
March 7, 2016: Clinical Journal of the American Society of Nephrology: CJASN
L Yessayan, A Shafiq, E Peterson, K Wells, Y Hu, L K Williams, D Lanfear
BACKGROUND: Calcineurin-inhibitor (CNI)-induced nephrotoxicity frequently complicates transplantation. African-Americans are at a greater risk of renal failure than the general population. We investigated whether race was an effect modifier of the relationship between CNI exposure and kidney function after nonrenal solid organ transplantation. METHODS: This is a retrospective cohort study of 1609 patients who underwent initial nonrenal solid organ transplantation between January 2000 and June 2012...
December 2015: Transplantation Proceedings
Sylvia J Wowro, Katharina R L Schmitt, Giang Tong, Felix Berger, Stephan Schubert
Post-transplant lymphoproliferative disorder is a severe complication in solid organ transplant recipients, which is highly associated with Epstein-Barr virus infection in pediatric patients and occasionally presents as Burkitt- or Burkitt-like lymphoma. The mammalian target of rapamycin (mTOR) pathway has been described as a possible antitumor target whose inhibition may influence lymphoma development and proliferation after pediatric transplantation. We treated Epstein-Barr virus positive (Raji and Daudi) and negative (Ramos) human Burkitt lymphoma derived cells with mTOR inhibitor everolimus alone and in combination with clinically relevant immunosuppressive calcineurin inhibitors (tacrolimus or cyclosporin A)...
January 2016: International Immunopharmacology
Hye One Kim, Yoon Seok Yang, Hyun Chang Ko, Gyung Moon Kim, Sang Hyun Cho, Young Joon Seo, Sang Wook Son, Jong Rok Lee, Joong Sun Lee, Sung Eun Chang, Jae We Che, Chun Wook Park
BACKGROUND: Topical calcineurin inhibitors (TCIs) have been successfully used to treat seborrheic dermatitis (SD) patients. Meanwhile, treatment of atopic dermatitis (AD) with low-dose, intermittent TCI has been proved to reduce disease flare-ups. This regimen is known as a maintenance treatment. OBJECTIVE: The aim of this trial was to investigate the efficacy and tolerability of a maintenance treatment with tacrolimus ointment in patients with facial SD. METHODS: During the initial stabilization period, patients with facial SD or AD applied 0...
October 2015: Annals of Dermatology
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
Rose Tompkins, William J Cole, Barry P Rosenzweig, Leon Axel, Sripal Bangalore, Anuradha Lala
Giant cell myocarditis is a rare and often fatal disease. The most obvious presentation often described in the literature is one of rapid hemodynamic deterioration due to cardiogenic shock necessitating urgent consideration of mechanical circulatory support and heart transplantation. We present the case of a 60-year-old man whose initial presentation was consistent with myopericarditis but who went on to develop a rapid decline in left ventricular systolic function without overt hemodynamic compromise or dramatic symptomatology...
2015: Case Reports in Cardiology
Christopher E Dandoy, Luke L Linscott, Stella M Davies, James L Leach, Kasiani C Myers, Javier El-Bietar, Ranjit S Chima, Abigail Pate, Adam Nelson, Gregory Wallace, Hector R Wong, Sonata Jodele
Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome characterized by vision changes, altered mental status, and seizures, typically caused by an acute rise in blood pressure. PRES has been reported after hematopoietic stem cell transplantation (HSCT) in association with hypertension from calcineurin inhibitors and corticosteroids. The imaging evaluation of PRES after HSCT in children and young adults has not been well described. We performed a retrospective review of all HSCT recipients presenting to the intensive care unit with new neurologic symptoms...
November 2015: Biology of Blood and Marrow Transplantation
D A Mandelbrot, J Alberú, A Barama, B A Marder, H T Silva, S M Flechner, A Flynn, C Healy, H Li, M A Tortorici, S L Schulman
This prospective, randomized, double-blind, placebo-controlled study evaluated the effects of ramipril on urinary protein excretion in renal transplant patients treated with sirolimus following conversion from a calcineurin inhibitor. Patients received ramipril or placebo for up to 6 weeks before conversion and 52 weeks thereafter. Doses were increased if patients developed proteinuria (urinary protein/creatinine ratio ≥0.5); losartan was given as rescue therapy for persistent proteinuria. The primary end point was time to losartan initiation...
December 2015: American Journal of Transplantation
E Safroneeva, S Vavricka, N Fournier, F Seibold, C Mottet, A Nydegger, J Ezri, A Straumann, G Rogler, A M Schoepfer
BACKGROUND: Studies that systematically assess change in ulcerative colitis (UC) extent over time in adult patients are scarce. AIM: To assess changes in disease extent over time and to evaluate clinical parameters associated with this change. METHODS: Data from the Swiss IBD cohort study were analysed. We used logistic regression modelling to identify factors associated with a change in disease extent. RESULTS: A total of 918 UC patients (45...
September 2015: Alimentary Pharmacology & Therapeutics
Scott R Solomon, Connie A Sizemore, Michelle Ridgeway, Xu Zhang, Judith Smith, Stacey Brown, H Kent Holland, Lawrence E Morris, Asad Bashey
Chronic graft-versus-host disease (cGVHD) is a significant determinant of overall outcome and quality of life in survivors of allogeneic hematopoietic cell transplantation. Standard initial therapy of cGVHD is based on prolonged use of corticosteroids and a calcineurin inhibitor and has not changed for over 3 decades, despite limited efficacy and long-term toxicity. Rituximab is an attractive agent for the upfront treatment of cGVHD because of its favorable toxicity profile, efficacy in steroid-refractory cGVHD, and ability to serve as a steroid-sparing agent in autoimmune diseases...
September 2015: Biology of Blood and Marrow Transplantation
Melanie Chong, Luz Fonacier
Atopic dermatitis (AD) is a chronic inflammatory skin condition that requires a manifold approach to therapy. The goal of therapy is to restore the function of the epidermal barrier and to reduce skin inflammation. This can be achieved with skin moisturization and topical anti-inflammatory agents, such as topical corticosteroids and calcineurin inhibitors. Furthermore, proactive therapy with twice weekly use of both topical corticosteroids and calcineurin inhibitors in previously affected areas has been found to reduce the time to the next eczematous flare...
December 2016: Clinical Reviews in Allergy & Immunology
Renaud Snanoudj, Claire Tinel, Christophe Legendre
During the past 10 years, minimization strategies have been legitimately initiated to decrease the many toxicities of calcineurin inhibitors, especially nephrotoxicity which was considered to be responsible for the majority of graft losses. Even though CNI-induced nephrotoxicity is undeniable, we have learned in the past 10 years that DSAs detected with solid-phase assays are excellent prognostic biomarkers in kidney transplantation (and in other organ transplantations as well) and that chronic antibody-mediated rejection has become the leading cause of graft loss...
August 2015: Transplant International: Official Journal of the European Society for Organ Transplantation
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