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Everolimus kidney transplantation

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https://www.readbyqxmd.com/read/28511172/donor-specific-anti-human-leukocyte-antigens-antibodies-acute-rejection-renal-function-and-histology-in-kidney-transplant-recipients-receiving-tacrolimus-and-everolimus
#1
Alexandra Ferreira, Claudia Felipe, Marina Cristelli, Laila Viana, Geovana Basso, Suelen Stopa, Juliana Mansur, Mayara Ivani, Adrieli Bessa, Priscila Ruppel, Wilson Aguiar, Erika Campos, Maria Gerbase-DeLima, Henrique Proença, Helio Tedesco-Silva, José Medina-Pestana
BACKGROUND: This analysis compared efficacy, renal function, and histology in kidney transplant recipients receiving tacrolimus (TAC) combined with everolimus (EVR) or mycophenolate (MPS). METHODS: This was a retrospective analysis from a randomized trial in kidney transplant recipients who received a single 3 mg/kg dose of rabbit antithymocyte globulin (r-ATG), TAC, EVR, and prednisone (PRED; r-ATG/EVR, n = 85), basiliximab (BAS), TAC, EVR, and PRED (BAS/EVR, n = 102) or BAS, TAC, MPS, and PRED (BAS/MPS, n = 101)...
May 17, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28508247/in-human-cell-cultures-everolimus-is-inferior-to-tacrolimus-in-inhibiting-cellular-alloimmunity-but-equally-effective-as-regards-humoral-alloimmunity
#2
Theodoros Eleftheriadis, Georgios Pissas, Maria Sounidaki, Georgia Antoniadi, Nikolaos Antoniadis, Vassilios Liakopoulos, Ioannis Stefanidis
PURPOSE: Acute cellular rejection is the major cause of immune-mediated graft failure early in the course of kidney transplantation, whereas chronic antibody-mediated rejection is a major contributor to graft loss in the late post-transplant phase. Based mainly on the results of short-term studies, the calcineurin inhibitor tacrolimus prevails over the mammalian target of rapamycin (mTOR) inhibitors. However, the toxicity profile of the two drug categories differs, making the interchange between them appealing...
May 15, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28507917/systemic-meta-analysis-assessing-the-short-term-applicability-of-early-conversion-to-mammalian-target-of-rapamycin-inhibitors-in-kidney-transplant
#3
Jayant Kumar, Isabella Reccia, Tomokazu Kusano, Bridson M Julie, Ajay Sharma, Ahmed Halawa
AIM: To consolidate the present evidence of effectiveness in renal functioning and graft survival following early introduction of mammalian target of rapamycin (mTOR) inhibitors with or without calcineurin inhibitors (CNIs) in renal transplant recipients. METHODS: We analysed the current literature following PROSPERO approval describing the role of immunosuppressive agent, mTOR inhibitors as an alternative to CNI within six months of renal transplant by searching the PubMed, EMBASE, Cochrane, Crossref, and Scopus using MeSH terms...
April 24, 2017: World Journal of Transplantation
https://www.readbyqxmd.com/read/28415888/bioengineered-gold-nanoparticles-targeted-to-mesenchymal-cells-from-patients-with-bronchiolitis-obliterans-syndrome-does-not-rise-the-inflammatory-response-and-can-be-safely-inhaled-by-rodents
#4
Emanuela Cova, Simona Inghilleri, Laura Pandolfi, Monica Morosini, Sara Magni, Miriam Colombo, Davide Piloni, Chiara Finetti, Gabriele Ceccarelli, Laura Benedetti, Maria Gabriella Cusella, Manuela Agozzino, Fabio Corsi, Raffaele Allevi, Simona Mrakic-Sposta, Sarah Moretti, Simona De Gregori, Davide Prosperi, Federica Meloni
The use of gold nanoparticles as drug delivery system represents a promising issue for diseases without effective pharmacological treatment due to insufficient local drug accumulation and excessive systemic toxicity. Bronchiolitis obliterans syndrome (BOS) represents about 70% of cases of chronic lung allograft dysfunction, the main challenge to long term lung transplantation. It is believed that due to repeated insults to epithelial bronchiolar cells local inflammatory response creates a milieu that favours epithelial mesenchymal transition and activation of local mesenchymal cells leading to airway fibro-obliteration...
April 18, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28405603/mtor-inhibition-by-everolimus-does-not-impair-closure-of-punch-biopsy-wounds-in-renal-transplant-patients
#5
Shelley B Dutt, Josephine Gonzales, Megan Boyett, Anne Costanzo, Peggy P Han, Steven Steinberg, Dianne B McKay, Julie M Jameson
BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are approved to prevent allograft rejection and control malignancy. Unfortunately, they are associated with adverse effects, such as wound healing complications that detract from more extensive use. There is a lack of prospective wound healing studies to monitor patients treated with mTOR inhibitors, such as everolimus or sirolimus, especially in nondiabetics. METHODS: Patients receiving everolimus with standard immunosuppressant therapy or standard immunosuppressant therapy without everolimus were administered 3-mm skin biopsy punch wounds in the left scapular region...
April 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28340831/pregnancy-and-delivery-in-the-sequel-of-kidney-transplantation-single-center-study-of-8-years-experience
#6
Y Yuksel, S Tekin, D Yuksel, I Duman, M Sarier, L Yucetin, E Turan, H Celep, T Ugurlu, M M Inal, Y H Asuman, A Demirbas
BACKGROUND: Depending on hyphothalamic, hyphophyseal, and gonadal axis dysfunction, anovulatory irregular cycles occur and the probability of pregnancy decreases in the patients with chronic kidney disease (CKD). Maternal mortality and morbidity rates are increased in CKD patients; the risk of premature delivery is 70% and the risk of preeclampsia is 40% more than normal among those with a creatine level of >2.5 mg/dL. METHODS: If a pregnancy is expected in the sequel of kidney transplantation (KT), a multidisciplinary team approach should be adopted and both the gynecologist and the nephrologist should follow the patient simultaneously...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28340820/role-of-everolimus-on-cardiac-functions-in-kidney-transplant-recipients
#7
U Cakir, G Alis, T Erturk, A H Karayagiz, U Karabulut, I Berber
BACKGROUND: Kidney transplantation is known to increase the survival of dialysis patients by ameloriating cardiac status, including both systolic and diastolic functions. We aimed to evaluate the role of immunosuppressive drug regimens on cardiac functions of kidney transplant recipients (KTRs). METHODS: We prospectively evaluated 120 KTRs immediately before and 1 year after the kidney transplantation, using tissue Doppler echocardiography. A triple immunosuppressive therapy including tacrolimus, mycophenoloic acid (MPA), and prednisolone was started for all patients...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28333860/cardiovascular-parameters-to-2-years-after-kidney-transplantation-following-early-switch-to-everolimus-without-calcineurin-inhibitor-therapy-an-analysis-of-the-randomized-elevate-study
#8
Hallvard Holdaas, Johan W de Fijter, Josep M Cruzado, Pablo Massari, Björn Nashan, John Kanellis, Oliver Witzke, Alex Gutierrez-Dalmau, Aydin Turkmen, Zailong Wang, Patricia Lopez, Peter Bernhardt, Jossy Kochuparampil, Markus van der Giet, Klaus Murbraech
BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors may confer cardioprotective advantages but clinical data are limited. METHODS: In the open-label ELEVATE trial, kidney transplant patients were randomized at 10-14 weeks posttransplant to convert from calcineurin inhibitor (CNI) to everolimus or remain on standard CNI therapy. Prespecified endpoints included left ventricular mass index (LVMi) and, in a subpopulation of patients, arterial stiffness as measured by pulse wave velocity (PWV)...
March 22, 2017: Transplantation
https://www.readbyqxmd.com/read/28332959/de-novo-donor-specific-antibody-formation-in-tacrolimus-based-mycophenolate-versus-mammalian-target-of-rapamycin-immunosuppressive-regimens
#9
Zain Mithani, Jane Gralla, Oluwafisayo Adebiyi, Patrick Klem, James E Cooper, Alexander C Wiseman
OBJECTIVES: De novo donor-specific antibody formation posttransplant is associated with decreased graft survival. It is not known whether mammalian target of rapamycin inhibitors may be advantageous or detrimental compared with mycophenolate in the prevention of de novo donor-specific antibody formation. MATERIALS AND METHODS: We compared 66 kidney and kidney-pancreas transplant recipients who received tacrolimus, mammalian target of rapamycin inhibitor, and prednisone (group 1; 36 of whom received everolimus and 30 of whom received sirolimus) versus 132 patients who received tacrolimus, mycophenolate, and prednisone (group 2) matched for age, sex, race, and type/timing of transplant from 2007 to 2012...
March 22, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28279567/optimizing-everolimus-exposure-when-combined-with-calcineurin-inhibitors-in-solid-organ-transplantation
#10
REVIEW
Teun van Gelder, Lutz Fischer, Fuad Shihab, Maria Shipkova
The mammalian target of rapamycin (mTOR) inhibitor everolimus is a narrow therapeutic index drug for which optimal exposure levels are essential. The consistent pharmacokinetic profile of everolimus allows trough concentration (C0) measurement to be an appropriate and reliable index for therapeutic drug monitoring (TDM). Exposure-response analyses of data from early fixed-dose trials demonstrated that rates of biopsy-proven acute rejection (BPAR) are significantly higher if everolimus C0 declines below 3 ng/mL, an observation confirmed in subsequent concentration-controlled trials...
February 27, 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28276629/improved-fetal-hemoglobin-with-mtor-inhibitor-based-immunosuppression-in-a-kidney-transplant-recipient-with-sickle-cell-disease
#11
N Gaudre, P Cougoul, P Bartolucci, G Dörr, A Bura-Riviere, N Kamar, A Del Bello
Fetal hemoglobin induction is a key point in the management of sickle cell disease (SCD). We report the case of a kidney transplant recipient with SCD who was treated with everolimus, a mammalian target of rapamycin inhibitor. At 10 months after initiating therapy, the patient's fetal hemoglobin level was dramatically increased (from 4.8% to 15%) and there was excellent tolerance to treatment.
March 9, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28247521/combination-of-leflunomide-and-everolimus-for-treatment-of-bk-virus-nephropathy
#12
Juli Jaw, Prue Hill, David Goodman
BK nephropathy (BKN) is a common cause of graft dysfunction following kidney transplantation. Minimization of immunosuppressive therapy remains the first line of therapy, but this may lead to rejection and graft loss. In some cases, despite lowering immunosuppression, BK infection can persist, leading to chronic damage and kidney failure. Currently, there is no specific anti-BK viral therapy. Recent in vitro experiments have demonstrated a reduction in BK viral replication when infected cells are treated with the combination of Leflunomide and Everolimus...
April 2017: Nephrology
https://www.readbyqxmd.com/read/28141897/association-of-clinical-events-with-everolimus-exposure-in-kidney-transplant-patients-receiving-low-doses-of-tacrolimus
#13
F Shihab, Y Qazi, S Mulgaonkar, K McCague, D Patel, V R Peddi, D Shaffer
A key objective in the use of immunosuppression following kidney transplantation is to attain the optimal balance between efficacy and safety. In a Phase IIIb, multi-center, randomized, open-label, non-inferiority study, incidence of clinical events, renal dysfunction and adverse events (AEs) were analyzed at 12 months in 309 de novo renal transplant recipients receiving everolimus (EVR), low-dose Tac (LTac) and prednisone. Cox proportional hazard regression modeling was used to estimate the probability of clinical events at specified combinations of time-normalized EVR and Tac trough concentrations...
January 31, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28134984/conversion-from-sirolimus-to-everolimus-in-long-term-liver-graft-recipients
#14
Nina Weiler, Nigar Bilge, Sven Troetschler, Johannes Vermehren, Andreas Anton Schnitzbauer, Eva Herrmann, Christoph Sarrazin, Stefan Zeuzem, Martin-Walter Welker
Immunosuppression by inhibition of the mechanistic target of rapamycin (mTOR) is a promising approach after liver transplantation. The mTOR inhibitor sirolimus was used in selected liver graft recipients despite safety concerns and lack of approval. Everolimus is another mTOR inhibitor approved after liver transplantation. It is currently unknown, whether conversion of sirolimus to everolimus is safe in long-term liver graft recipients. Long-term liver graft recipients treated with sirolimus were converted to everolimus...
January 30, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28125504/therapeutic-drug-monitoring-of-everolimus-comparability-of-concentrations-determined-by-2-immunoassays-and-a-liquid-chromatography-tandem-mass-spectrometry-method
#15
Maria Shipkova, Sonja Rapp, Raül Rigo-Bonnin, Eberhard Wieland, Andreas Peter
BACKGROUND: Therapeutic drug monitoring is recommended to guide therapy with the immunosuppressant everolimus (EVL) in solid organ transplantation to prevent rejections and to limit toxicity. For therapeutic drug monitoring, predose EVL concentrations are measured in whole blood mainly by liquid chromatography tandem mass spectrometry (LC-MS/MS). In addition, 2 immunoassays [Quantitative Microsphere System (QMS) EVL and Elecsys EVL] are commercially available. The aim of this study was to evaluate the comparability of EVL results determined with the 2 immunoassays and a validated LC-MS/MS test using samples from kidney, liver, and heart transplant (KT, LT, and HT, respectively) recipients...
April 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28121741/effect-of-early-everolimus-facilitated-reduction-of-tacrolimus-on-efficacy-and-renal-function-in-de-novo-liver-transplant-recipients-24-month-results-for-the-north-american-subpopulation
#16
William C Chapman, Robert S Brown, Kenneth D Chavin, Debra Sudan, Baburao Koneru, Guido Junge, Gaohong Dong, Dharmesh Patel, Lewis Teperman, John J Fung
BACKGROUND: A recent randomized phase III study of 719 de novo liver transplant recipients showed that early everolimus plus reduced-dose tacrolimus (EVR + rTAC) led to significantly better kidney function than standard TAC (TAC-C), without compromising efficacy. In that study, patients from North America (n = 211) had increased risk factors for posttransplant renal insufficiency at study start, relative to patients from Europe and rest of world (eg, worse renal function, more diabetes, older age)...
February 2017: Transplantation
https://www.readbyqxmd.com/read/28119255/limitations-of-current-liver-transplant-immunosuppressive-regimens-renal-considerations
#17
Wei Zhang, John Fung
BACKGROUND: The use of calcineurin inhibitor (CNI)-based immunosuppressive regimens following liver transplantation (LTx) has improved the outcomes of the recipients. However, CNI has nephrotoxicity and causes short- and long-term renal complications. The progressive structural changes can be irreversible in the long-term, leading to chronic kidney dysfunction. The present review was to evaluate the different strategies of CNI application to renal function in liver recipients. DATA SOURCES: PubMed database was searched for relevant articles in English on the issue of immunosuppressive regimen and kidney injury that related to early minimization of CNI after LTx...
February 2017: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/28109543/the-risk-of-cancer-in-kidney-transplant-recipients-may-be-reduced-in-those-maintained-on-everolimus-and-reduced-cyclosporine
#18
Wai H Lim, Graeme R Russ, Germaine Wong, Helen Pilmore, John Kanellis, Steven J Chadban
Kidney transplant recipients are at a high risk of developing cancers after transplantation. Switching from calcineurin inhibitors to sirolimus has been shown to prevent secondary nonmelanoma skin cancer but whether everolimus with reduced exposure to calcineurin inhibitors has similar anti-cancer effects remains unknown. Therefore, we compared the risk of incident cancer over seven years of follow-up among kidney transplant recipients randomized to everolimus plus reduced exposure cyclosporine versus mycophenolate sodium and standard exposure cyclosporine...
January 18, 2017: Kidney International
https://www.readbyqxmd.com/read/28107397/efficacy-and-safety-of-everolimus-for-maintenance-immunosuppression-of-kidney-transplantation-a-meta-analysis-of-randomized-controlled-trials
#19
Jinyu Liu, Dong Liu, Juan Li, Lan Zhu, Chengliang Zhang, Kai Lei, Qiling Xu, Ruxu You
BACKGROUND: Conversion to everolimus is often used in kidney transplantation to overcome calcineurin inhibitor (CNI) nephrotoxicity but there is conflicting evidence for this approach. OBJECTIVES: To investigate the benefits and harm from randomized clinical trials (RCTs) involving the conversion from CNI to everolimus after kidney transplantation. METHODS: Databases were searched up to March 2016. Two reviewers independently assessed trials for eligibility and quality, and extracted data...
2017: PloS One
https://www.readbyqxmd.com/read/28104155/immunosuppression-modification-by-everolimus-with-minimization-of-calcineurin-inhibitors-recovers-kidney-graft-function-even-in-patients-with-very-late-conversion-and-also-with-poor-graft-function
#20
M Nojima, Y Yamada, Y Higuchi, K Shimatani, A Kanematsu, S Yamamoto
BACKGROUND: Although kidney graft survival within 5 years after transplantation is now achieved in >95% of recipients, chronic graft deterioration remains a factor limiting long-term survival. Chronic nephrotoxicity induced by calcineurin inhibitors (CNIs) is one of the major causes of chronic graft injury; thus, minimization of CNIs by administration of everolimus (EVR) is expected to relieve their toxic effects. METHODS: Fifty-six kidney transplant recipients receiving CNI-based immunosuppression (tacrolimus, n = 34; cyclosporine, n = 22) were analyzed...
January 2017: Transplantation Proceedings
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