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Everolimus renal transplantation

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https://www.readbyqxmd.com/read/27862340/everolimus-with-early-withdrawal-or-reduced-dose-calcineurin-inhibitors-improves-renal-function-in-liver-transplant-recipients-a-systematic-review-and-meta-analysis
#1
Michael Lin, Sahil Mittal, Farhad Sahebjam, Abbas Rana, Gagan K Sood
Calcineurin inhibitors (CNI) are the mainstay of immunosuppression after liver transplantation (LT), but CNIs are associated with significant nephrotoxicity. Recently, mTOR inhibitors such as sirolimus and everolimus (EVR) have been used with or without CNIs in LT recipients for their renal-sparing effect. We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) that examined the effect of EVR with CNI minimization or withdrawal on renal function in LT recipients. RCT of primary adult LT recipients with baseline GFR >30 mL/min who received EVR with CNI minimization or withdrawal were included...
November 16, 2016: Clinical Transplantation
https://www.readbyqxmd.com/read/27798513/longitudinal-pharmacokinetics-of-everolimus-when-combined-with-low-level-of-tacrolimus-in-elderly-renal-transplant-recipients
#2
Elias David-Neto, Fabiana Agena, Fernanda Ramos, Ana Heloisa Triboni, Paschoalina Romano, Persio de Almeida Rezende Ebner, Venceslau Coelho, Nelson Zocoler Galante, Francine Carvalinho Lemos
BACKGROUND: Although the proportion of elderly patients among renal transplant recipients has increased, pharmacokinetic (PK) studies of immunosuppressants rarely include older patients. METHODS: We studied 12-hours everolimus (EVL) PK in 16 elderly renal transplant recipients (all caucasians; 10 males; mean age, 64±2 years, (61-71y), in 4 separate time-points (at 7, 30, 60 and 150 days) after EVL introduction, corresponding to a mean post renal-transplantation day: PK1 (43±4days), PK2 (65±7 days), PK3 (106±17 days) and PK4 (206±40 days)...
October 28, 2016: Transplantation
https://www.readbyqxmd.com/read/27797804/everolimus-associated-stomatitis-in-a-patient-who-had-renal-transplant
#3
Yisi D Ji, Ali Aboalela, Alessandro Villa
Everolimus is used as an immunosuppressant in renal allograft transplant rejection and in metastatic breast cancer treatment. One side effect of everolimus is stomatitis, referred to as mammalian target of rapamycin inhibitor-associated stomatitis. This side effect can affect treatment course and contribute to discontinuation of therapy or dose reduction, previously reported in the treatment of metastatic breast cancer. Here, we present a case of everolimus-associated stomatitis with a novel management method with intralesional triamcinolone that allows for continuous course of everolimus...
October 19, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27793122/acute-pancreatitis-associated-with-everolimus-after-kidney-transplantation-a-case-report
#4
Francesco Fontana, Gianni Cappelli
BACKGROUND: Acute pancreatitis (AP) following KT is a rare and often fatal complication of the early post-transplant period. Common causative factors for AP are rare after KT; anti-rejection drugs as CyA, prednisone and MMF have been implicated, although evidence is not strong and we found no reports on possible causative role for mTOR inhibitors. CASE PRESENTATION: A 55-year-old Caucasian man with end-stage renal disease due to idiopathic membrano-prolipherative glomerulonephritis underwent single kidney transplantation (KT) from cadaveric donor...
October 28, 2016: BMC Nephrology
https://www.readbyqxmd.com/read/27775865/efficacy-and-safety-of-everolimus-plus-low-dose-tacrolimus-versus-mycophenolate-mofetil-plus-standard-dose-tacrolimus-in-de-novo-renal-transplant-recipients-12-month-data
#5
Y Qazi, D Shaffer, B Kaplan, D Kim, F L Luan, V R Peddi, F Shihab, S Tomlanovich, S Yilmaz, K McCague, D Patel, S Mulgaonkar
In this 12-month, multicenter, randomized, open-label, non-inferiority study, de novo renal transplant recipients (RTxRs) were randomized (1:1) to receive everolimus plus low-dose tacrolimus (EVR+LTac) or mycophenolate mofetil plus standard-dose Tac (MMF+STac) with induction therapy (basiliximab or rabbit anti-thymocyte globulin). Non-inferiority of composite efficacy failure rate (tBPAR/graft loss/death/loss to follow-up) in EVR+LTac versus MMF+STac, was missed by 1.4% considering the non-inferiority margin of 10% (24...
October 24, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27742336/safety-and-efficacy-of-early-everolimus-when-calcineurin-inhibitors-are-not-recommended-in-orthotopic-liver-transplantation
#6
M Gastaca, I Bilbao, M Jimenez, J Bustamante, C Dopazo, R Gonzalez, R Charco, J Santoyo, J Ortiz de Urbina
Our aim was to study the safety and efficacy of immunosuppression with everolimus (EVL) within the 1st month after orthotopic liver transplantation (LT) when calcineurin inhibitors are not recommended. For this purpose, 28 recipients who had been treated with EVL within the 1st month after adult LT were eligible to enter in a retrospective multicenter study. Patients were followed up for 12 months after LT. EVL therapy was initiated at a median of 14 days (range, 4-24) after LT. The reason for early EVL was neurotoxicity in 14 cases, renal dysfunction in 12, and acute cellular rejection combined with renal impairment in 2...
September 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27648523/controlled-randomized-study-comparing-the-cardiovascular-profile-of-everolimus-with-tacrolimus-in-renal-transplantation
#7
Josep M Cruzado, Julio Pascual, Ana Sánchez-Fructuoso, Daniel Serón, Joan M Díaz, Manuel Rengel, Federico Oppenheimer, Domingo Hernández, Alexandra Paravisini, Núria Saval, José M Morales
Left ventricular hypertrophy (LVH) regression after kidney transplantation may be influenced by immunosuppression. In a 24-month open-label, multicenter, phase-IV study, 71 kidney allograft recipients without previous acute rejection, showing eGFR >40 ml/min and proteinuria <500 mg/day and between 6 months and 3 years post-transplantation, were randomized to receive everolimus (EVR) + mycophenolic acid (MPA) or were maintained on tacrolimus (TAC) + MPA. The aim was to assess whether the conversion to EVR could reduce left ventricular mass index (LVMi) at month-24...
September 20, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27639190/early-conversion-to-prednisolone-everolimus-as-an-alternative-weaning-regimen-associates-with-beneficial-renal-transplant-histology-and-function-the-randomized-controlled-mecano-trial
#8
F J Bemelman, J W de Fijter, J Kers, C Meyer, H Peters-Sengers, E F de Maar, K A M I van der Pant, A P J de Vries, J-S Sanders, A Zwinderman, M M Idu, S Berger, M E J Reinders, C Krikke, I M Bajema, M C van Dijk, I J M Ten Berge, J Ringers, J Lardy, D Roelen, D-J Moes, S Florquin, J J Homan van der Heide
In renal transplantation, use of calcineurin inhibitors (CNIs) is associated with nephrotoxicity and immunosuppression with malignancies and infections. This trial aimed to minimize CNI exposure and total immunosuppression while maintaining efficacy. We performed a randomized controlled, open-label multicenter trial with early cyclosporine A (CsA) elimination. Patients started with basiliximab, prednisolone (P), mycophenolate sodium (MPS), and CsA. At 6 months, immunosuppression was tapered to P/CsA, P/MPS, or P/everolimus (EVL)...
September 17, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27601910/profile-of-everolimus-in-the-treatment-of-tuberous-sclerosis-complex-an-evidence-based-review-of-its-place-in-therapy
#9
REVIEW
Jamie K Capal, David Neal Franz
Tuberous sclerosis complex (TSC) is a relatively rare genetic disorder, affecting one in 6,000 births. Mammalian target of rapamycin (mTOR) inhibitors, such as everolimus, which have been previously used to prevent solid organ transplant rejection, augment anticancer treatment regimens, and prevent neovascularization of artificial cardiac stents, are now approved for treating TSC-related manifestations, such as subependymal giant cell astrocytomas and renal angiomyolipomas. The use of everolimus in treating subependymal giant cell astrocytomas is supported by long-term Phase II and III clinical trials...
2016: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/27586504/the-influence-of-exposure-to-immunosuppressive-treatment-during-pregnancy-on-renal-function-and-rate-of-apoptosis-in-native-kidneys-of-female-wistar-rats
#10
Joanna Kabat-Koperska, Agnieszka Kolasa-Wołosiuk, Irena Baranowska-Bosiacka, Krzysztof Safranow, Danuta Kosik-Bogacka, Izabela Gutowska, Anna Pilutin, Edyta Gołembiewska, Karolina Kędzierska, Kazimierz Ciechanowski
Pregnancy puts a significant additional strain on kidneys. The aim of our study was to investigate the impact of immunosuppressive drugs on changes in native kidneys in female Wistar rats after exposure during pregnancy. The study was conducted on 32 dams, subjected to immunosuppressive regimens commonly used in the therapy of human kidney transplant recipients (cyclosporine A, mycophenolate mofetil and prednisone; tacrolimus, mycophenolate mofetil and prednisone; cyclosporine A, everolimus and prednisone)...
November 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27578428/immunosuppressive-therapy-for-kidney-transplantation-in-adults-a-systematic-review-and-economic-model
#11
Tracey Jones-Hughes, Tristan Snowsill, Marcela Haasova, Helen Coelho, Louise Crathorne, Chris Cooper, Ruben Mujica-Mota, Jaime Peters, Jo Varley-Campbell, Nicola Huxley, Jason Moore, Matt Allwood, Jenny Lowe, Chris Hyde, Martin Hoyle, Mary Bond, Rob Anderson
BACKGROUND: End-stage renal disease is a long-term irreversible decline in kidney function requiring renal replacement therapy: kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation, followed by immunosuppressive therapy (induction and maintenance therapy) to reduce the risk of kidney rejection and prolong graft survival. OBJECTIVES: To review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect(®), Novartis Pharmaceuticals UK Ltd) and rabbit anti-human thymocyte immunoglobulin (rATG) (Thymoglobulin(®), Sanofi) as induction therapy, and immediate-release tacrolimus (TAC) (Adoport(®), Sandoz; Capexion(®), Mylan; Modigraf(®), Astellas Pharma; Perixis(®), Accord Healthcare; Prograf(®), Astellas Pharma; Tacni(®), Teva; Vivadex(®), Dexcel Pharma), prolonged-release tacrolimus (Advagraf(®) Astellas Pharma), belatacept (BEL) (Nulojix(®), Bristol-Myers Squibb), mycophenolate mofetil (MMF) (Arzip(®), Zentiva; CellCept(®), Roche Products; Myfenax(®), Teva), mycophenolate sodium (MPS) (Myfortic(®), Novartis Pharmaceuticals UK Ltd), sirolimus (SRL) (Rapamune(®), Pfizer) and everolimus (EVL) (Certican(®), Novartis) as maintenance therapy in adult renal transplantation...
August 2016: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/27569936/pilot-randomized-trial-of-tacrolimus-everolimus-vs-tacrolimus-enteric-coated-mycophenolate-sodium-in-adult-primary-kidney-transplant-recipients-at-a-single-center
#12
G Ciancio, P Tryphonopoulos, J J Gaynor, G Guerra, J Sageshima, D Roth, L Chen, W Kupin, A Mattiazzi, L Tueros, S Flores, L Hanson, R H Powell, P Ruiz, R Vianna, G W Burke
BACKGROUND: Recent studies suggest that the combination of tacrolimus (TAC) and everolimus (EVL) could become a viable option for use as standard maintenance immunosuppression in non-highly sensitized kidney transplant recipients. METHODS: We conducted a single-center, open-label, randomized pilot trial comparing two maintenance immunosuppression regimens in non-highly sensitized, adult, primary kidney transplant recipients: (TAC/EVL, Group A) vs our standard maintenance regimen of TAC plus enteric-coated mycophenolate mofetil (TAC/EC-MPS, Group B)...
July 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27557331/immunosuppressive-therapy-for-kidney-transplantation-in-children-and-adolescents-systematic-review-and-economic-evaluation
#13
Marcela Haasova, Tristan Snowsill, Tracey Jones-Hughes, Louise Crathorne, Chris Cooper, Jo Varley-Campbell, Ruben Mujica-Mota, Helen Coelho, Nicola Huxley, Jenny Lowe, Jan Dudley, Stephen Marks, Chris Hyde, Mary Bond, Rob Anderson
BACKGROUND: End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation followed by induction and maintenance immunosuppressive therapy to reduce the risk of kidney rejection and prolong graft survival. OBJECTIVES: To systematically review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect,(®) Novartis Pharmaceuticals) and rabbit antihuman thymocyte immunoglobulin (Thymoglobuline,(®) Sanofi) as induction therapy and immediate-release tacrolimus [Adoport(®) (Sandoz); Capexion(®) (Mylan); Modigraf(®) (Astellas Pharma); Perixis(®) (Accord Healthcare); Prograf(®) (Astellas Pharma); Tacni(®) (Teva); Vivadex(®) (Dexcel Pharma)], prolonged-release tacrolimus (Advagraf,(®) Astellas Pharma); belatacept (BEL) (Nulojix,(®) Bristol-Myers Squibb), mycophenolate mofetil (MMF) [Arzip(®) (Zentiva), CellCept(®) (Roche Products), Myfenax(®) (Teva), generic MMF is manufactured by Accord Healthcare, Actavis, Arrow Pharmaceuticals, Dr Reddy's Laboratories, Mylan, Sandoz and Wockhardt], mycophenolate sodium, sirolimus (Rapamune,(®) Pfizer) and everolimus (Certican,(®) Novartis Pharmaceuticals) as maintenance therapy in children and adolescents undergoing renal transplantation...
August 2016: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/27518575/differential-antitumoral-properties-and-renal-associated-tissue-damage-induced-by-tacrolimus-and-mammalian-target-of-rapamycin-inhibitors-in-hepatocarcinoma-in-vitro-and-in-vivo-studies
#14
Elena Navarro-Villarán, José Tinoco, Granada Jiménez, Sheila Pereira, Jize Wang, Sara Aliseda, María A Rodríguez-Hernández, Raúl González, Luís M Marín-Gómez, Miguel A Gómez-Bravo, Francisco J Padillo, José M Álamo-Martínez, Jordi Muntané
Orthotopic liver transplantation (OLT) is the recommended treatment for patients at early stages of hepatocarcinoma (HCC) with potential portal hypertension and/or bilirubinemia, but without vascular-associated diseases. The patients are receiving immunosuppressive therapy to reduce graft rejection, but differential side effects have been related to calcineurin and mTOR inhibitor administration regarding tumor recurrence and nephrotoxicity. The in vitro studies showed that Tacrolimus exerted a more potent pro-apoptotic effect than Everolimus (Huh 7>Hep 3B>HepG2), being sirolimus only active in Hep3B cell line...
2016: PloS One
https://www.readbyqxmd.com/read/27513345/ingenol-mebutate-vs-daylight-photodynamic-therapy-in-a-kidney-transplant-recipient
#15
Michael Mühlstädt
We present the case of a 73-year-old male patient who had received a first renal transplant at 36 years and a second one at the age of 55 years. He is currently under immunosuppression with everolimus 2.5 mg/day and prednisone 5 mg/day. The patient presented with multiple actinic keratoses on both cheeks and the forehead and received treatment by ingenol mebutate 150 µg/g gel daily on 3 consecutive days on his right cheek and methyl aminolevulinate (MAL) photodynamic therapy activated by daylight (MAL-dPDT) on the forehead and the left cheek...
2016: Dermatology: International Journal for Clinical and Investigative Dermatology
https://www.readbyqxmd.com/read/27496505/kaposi-sarcoma-in-the-genital-area-in-a-kidney-transplant-patient-a%C3%A2-case-report-and-literature-review
#16
B Imko-Walczuk, M Kielbowicz, J Malyszko, J Malyszko, M Barczyk, A Debska-Slizien, M Mysliwiec, B Rutkowski
BACKGROUND: Kaposi sarcoma (KS) is a cancer with an incidence in patients after transplantation (Tx) that is 500 times greater than that in the healthy population. The risk of KS increases significantly during therapy, especially when immunosuppressive therapy with cyclosporine A (CsA) is used. Most cases of KS develop during the first 2 years after transplantation. After a KS diagnosis, it is recommended to reduce the doses of immunosuppressive medications. Conversion of immunosuppressive treatment into mammalian target of rapamycin (m-TOR) inhibitors is strongly suggested...
June 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27495768/use-of-everolimus-in-liver-transplantation-recommendations-from-a-working-group
#17
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, mTOR inhibitors have received considerable attention as immunosuppressants as they are associated with a more favorable renal profile vs. CNI, as well as anti-proliferative activity in clinical studies. Comprehensive guidelines on use of everolimus (EVR) in LT are still lacking...
August 5, 2016: Transplantation
https://www.readbyqxmd.com/read/27495747/recent-advances-in-mammalian-target-of-rapamycin-inhibitor-use-in-heart-and-lung-transplantation
#18
Nowell M Fine, Sudhir S Kushwaha
The mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus are increasingly used in cardiothoracic transplantation. Several recent clinical trials have demonstrated their efficacy in combination with reduced cyclosporine dosing in de novo heart transplant recipients, in particular with everolimus. A number of other studies have demonstrated their efficacy for improving renal function and reducing calcineurin inhibitor use, attenuating cardiac allograft vasculopathy progression and reducing cytomegalovirus infections in maintenance heart transplant populations...
December 2016: Transplantation
https://www.readbyqxmd.com/read/27403615/antineoplastic-treatment-and-renal-injury-an-update-on-renal-pathology-due-to-cytotoxic-and-targeted-therapies
#19
Megan L Troxell, John P Higgins, Neeraja Kambham
Cancer patients experience kidney injury from multiple sources, including the tumor itself, diagnostic procedures, hypovolemia, infection, and drug exposure, superimposed upon baseline chronic damage. This review will focus on cytotoxic or targeted chemotherapy-associated renal injury. In this setting, tubulointerstitial injury and thrombotic microangiopathy (vascular injury) are more common than other forms of kidney injury including glomerular. Cisplatin, pemetrexed, and ifosfamide are well-known causes of acute tubular injury/necrosis...
September 2016: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/27338360/role-of-mtor-inhibitors-in-kidney-disease
#20
REVIEW
Moto Kajiwara, Satohiro Masuda
The first compound that inhibited the mammalian target of rapamycin (mTOR), sirolimus (rapamycin) was discovered in the 1970s as a soil bacterium metabolite collected on Easter Island (Rapa Nui). Because sirolimus showed antiproliferative activity, researchers investigated its molecular target and identified the TOR1 and TOR2. The mTOR consists of mTOR complex 1 (mTORC1) and mTORC2. Rapalogues including sirolimus, everolimus, and temsirolimus exert their effect mainly on mTORC1, whereas their inhibitory effect on mTORC2 is mild...
2016: International Journal of Molecular Sciences
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