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timing of initiation of calcineurin inhibitors

Sophie Girerd, Frédéric Jaisser
Although patient survival is significantly improved by kidney transplantation (KT) in comparison with dialysis, it remains significantly lower than that observed in the general population. Graft function is one of the major determinants of patient survival after KT. Mineralocorticoid receptor antagonists (MRAs) could be of particular interest in this population to improve graft function and treat or prevent cardiovascular (CV) complications. In KT, ischaemia/reperfusion injury is a major factor involved in delayed graft function, which is often associated with inferior long-term graft survival...
April 17, 2018: Nephrology, Dialysis, Transplantation
Nalinee Saiprasertkit, Camila H Nihei, Joanne M Bargman
BACKGROUND: In many dialysis programs, there is resistance to initiating peritoneal dialysis (PD) in liver transplant patients needing renal replacement therapy. This retrospective study reviews the outcome of PD in liver transplant patients at a major transplantation and dialysis center. METHOD: We performed a retrospective cohort study in patients who underwent liver transplants and received PD between 1991 and 2016. Patient demographics, laboratory parameters, and adverse events were collected from our electronic database...
January 2018: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
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
Y Han, S Q DU, H J Xiao, Y Zhou, J Ding, J J Ding, Y M Cui
OBJECTIVE: Tacrolimus prolonged-release(PR) formulation is a new once-daily formulation of the calcineurin inhibitor tacrolimus, which is currently used in adult liver or kidney transplant patients,and is also gradually widely used in children with nephrotic syndrome.The present study was undertaken to preliminarily investigate the pharmacokinetic characteristics of tacrolimus PR in pediatric nephrotic syndrome recipients. METHODS: This single-center open-label prospective study was performed in pediatric nephrotic syndrome recipients...
October 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
Douglas A Jabs
The uveitides are a collection of more than 30 diseases characterized by intraocular inflammation. Many cases of juvenile idiopathic arthritis-associated uveitis, many cases of intermediate uveitis, and most cases of posterior and panuveitides requiring treatment are treated with corticosteroids and immunosuppression. Disease-specific, time-updated modeling of clinical data for several uveitides suggests superior prevention of ocular complications and visual outcomes with immunosuppression. These studies also suggest that oral corticosteroids at doses low enough for safe long-term therapy (i...
February 2018: Ophthalmology
Mei-Ling Yee, Hui-Hui Tan
In recent years, the use of mammalian target of rapamycin inhibitors has gained traction in their use as alternative or adjunct immunosuppressants in the post-liver transplantation (LT) setting. The efficacy of everolimus (EVR) in de novo LT is established and a reasonable time to initiate EVR is 30 d from LT surgery. Initiating EVR early post-LT allows for calcineurin inhibitor (CNI) reduction, thus reducing nephrotoxicity in LT recipients. However, data is inadequate on the appropriate timing for conversion from CNI to EVR maintenance in order to achieve optimal renoprotective effect without compromising drug efficacy...
August 18, 2017: World Journal of Hepatology
Carlo J Iasella, Ryan J Winstead, Cody A Moore, Bruce A Johnson, Ayelet T Feinberg, Matthew R Morrell, J W Awori Hayanga, Elizabeth A Lendermon, Adriana Zeevi, John F McDyer, Christopher R Ensor
BACKGROUND: Traditional immunosuppressive regimens (ISR) used in lung transplantation rely on calcineurin inhibitors (CNI) that occasionally cause severe adverse reactions necessitating discontinuation. Belatacept is a novel costimulation antagonist approved for use in renal transplantation which lacks data in lung transplantation. This series aims to describe the response to belatacept ISR in 11 lung transplantation recipients after CNI failure. METHODS: Single-center, retrospective medical record review of adult lung transplant recipients (LTR) before and after conversion to belatacept-based ISR...
January 2018: Transplantation
J S Costa, E Ferreira, R Leal, N Bota, C Romãozinho, V Sousa, C Marinho, L Santos, F Macário, R Alves, J Pratas, M Campos, A Figueiredo
BACKGROUND: Polyomavirus nephropathy (BKVN) is an important cause of chronic allograft dysfunction (CAD). Recipient determinants (male sex, white race, and older age), deceased donation, high-dose immunosuppression, diabetes, delayed graft function (DGF), cytomegalovirus infection, and acute rejection (AR) are risk factors. Reducing immunosuppression is the best strategy in BKVN. The objective of our study was to evaluate CAD progression after therapeutic strategies in BKVN and risk factors for graft loss (GL)...
May 2017: Transplantation Proceedings
Nils Heits, Dalibor Keserovic, Niclas Mund, Nicola Ehmke, Alexander Bernsmeier, Alexander Hendricks, Rainer Gunther, Karsten Witt, Thomas Becker, Felix Braun
BACKGROUND: Neurological disorders due to calcineurin inhibitor (CNI) treatment pose a well-known problem after liver transplantation (LTx). In this study, the impact of CNIs on cognitive functioning during maintenance therapy was analyzed. A possible improvement of cognitive functioning, compliance and health-related quality of life (HRQoL) after conversion to a once-daily tacrolimus formulation was prospectively assessed. METHODS: In a cross-section analysis cognitive functioning of living donors (LD), waiting list patients and LTx patients was tested using a 4 times trail making test (4-TTMT)...
April 2017: Transplantation Direct
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...
February 2017: 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...
February 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
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