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https://www.readbyqxmd.com/read/28934936/transitional-cell-carcinoma-involving-graft-kidney-in-a-kidney-transplant-recipient-a-case-report
#1
Yu Ah Hong, Hyeon Seok Hwang, Hae Joung Sul, Suk Young Kim, Yoon Kyung Chang
BACKGROUND: Kidney transplantation (KT) is the treatment option for patients with end stage renal disease (ESRD) to prolong survival and improve quality of life. Although the use of potent immunosuppressive agents increases graft survival in kidney transplantation recipients (KTRs), it may lead to the development of malignancy, including transitional cell carcinoma (TCC). TCC developing in the pelvis of graft kidney is very rare in KTRs. CASE PRESENTATION: A 40-year-old male visited hospital with complaints of nausea, vomiting and gross hematuria...
September 21, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28931653/combined-ox40l-and-mtor-blockade-controls-effector-t-cell-activation-while-preserving-treg-reconstitution-after-transplant
#2
Victor Tkachev, Scott N Furlan, Benjamin Watkins, Daniel J Hunt, Hengqi Betty Zheng, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, John B Schell, Katie Zeleski, Alison Yu, Ian Kirby, Sarah Cooley, Jeffrey S Miller, Bruce R Blazar, Duncan Casson, Phil Bland-Ward, Leslie S Kean
A critical question facing the field of transplantation is how to control effector T cell (Teff) activation while preserving regulatory T cell (Treg) function. Standard calcineurin inhibitor-based strategies can partially control Teffs, but breakthrough activation still occurs, and these agents are antagonistic to Treg function. Conversely, mechanistic target of rapamycin (mTOR) inhibition with sirolimus is more Treg-compatible but is inadequate to fully control Teff activation. In contrast, blockade of OX40L signaling has the capacity to partially control Teff activation despite maintaining Treg function...
September 20, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28927230/multi-azole-resistant-strains-of-cryptococcus-neoformans-var-grubii-isolated-from-a-flz-resistant-strain-by-culturing-in-medium-containing-voriconazole
#3
Rui Kano, Miki Okubo, Atsuhiko Hasegawa, Hiroshi Kamata
A Cryptococcus neoformans var. grubii strain, NUBS14020, was the first fluconazole (FLZ)-resistant strain isolated from a feline cryptococcosis. Subsequent work demonstrated that multi-azole-resistant strains are readily isolated from FLZ-resistant strains by culturing in medium containing voriconazole (VRZ). The resulting clones were assessed for mutation and expression of known target genes, including the loci encoding lanosterol 14-α demethylase (ERG11), an ATP-binding cassette (ABC) transporter (AFR1), or a multidrug efflux pump (MEP); mutation and/or overexpression of these genes is known to be associated with azole resistance...
September 11, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/28925592/defining-a-microrna-mrna-interaction-map-for-calcineurin-inhibitor-induced-nephrotoxicity
#4
Christopher J Benway, John Iacomini
Calcineurin inhibitors induce nephrotoxicity through poorly understood mechanisms thereby limiting their use in transplantation and other diseases. Here we define a microRNA (miRNA)-messenger RNA (mRNA) interaction map that facilitates exploration into the role of miRNAs in cyclosporine-induced nephrotoxicity (CIN) and the gene pathways they regulate. Using photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP), we isolated RNAs associated with Argonaute 2 in the RNA-Induced Silencing Complex (RISC) of cyclosporine A (CsA) treated and control human proximal tubule cells and identified mRNAs undergoing active targeting by miRNAs...
September 19, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28923863/synergistic-effects-of-tacrolimus-and-azoles-against-exophiala-dermatitidis
#5
Lujuan Gao, Yi Sun, Chengyan He, Tongxiang Zeng, Ming Li
In vitro interactions of tacrolimus, a calcineurin inhibitor, and azoles including itraconazole, voriconazole, and posaconazole against planktonic cells and biofilms of Exophiala dermatitidis were assessed via broth microdilution checkerboard technique. A total of 16 clinical isolates were studied. The results revealed favorable synergistic inhibitory activity between tacrolimus and itraconazole, voriconazole, or posaconazole against planktonic cells of E. dermatitidis However, limited synergism was observed against biofilms of E...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28923650/does-renal-tubular-injury-induced-local-tissue-hypoxia-involve-post-transplantation-erythrocytosis
#6
A Unal, S Ata, C Karakurkcu, M Z Ciraci, I Kocyigit, M H Sipahioglu, B Tokgoz, O Oymak
BACKGROUND: The pathogenesis of post-transplantation erythrocytosis (PTE) is not well understood and appears to be multifactorial. Our hypothesis in this study was that several factors, including toxicity of calcineurin inhibitor, immunologic factors, and chronic allograft nephropathy, can trigger local tissue hypoxia in peritubular interstitium, which is where production of erythropoietin (EPO) takes place. This local interstitial tissue hypoxia can cause an increase in renal EPO production, which induces the development of PTE...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28923619/ten-year-follow-up-of-pharmacokinetics-guided-very-early-cyclosporine-minimization-synchronized-with-everolimus-initiation-in-de-novo-kidney-transplantation
#7
V Sumethkul, P Tankee, S Worawichawong, S Jirasiritham
BACKGROUND: Minimization of calcineurin inhibitor (CNI) from the 1st week after kidney transplantation (KT) may reduce the risk of CNI nephrotoxicity. METHODS: Ten de novo KT recipients who received full exposure cyclosporine (CsA) and prednisolone as initial therapy were enrolled. Initial CsA minimization was 50% and started at day 7 after KT. This was synchronized with everolimus (EVL) initiation. Target trough level of EVL was 3-8 ng/mL. Pharmacokinetics studies of CsA and EVL were studied at week 4...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28921505/nfatc1-activation-by-dna-hypomethylation-in-chronic-lymphocytic-leukemia-correlates-with-clinical-staging-and-can-be-inhibited-by-ibrutinib
#8
Christine Wolf, Angela Garding, Katharina Filarsky, Jasmin Bahlo, Sandra Robrecht, Natalia Becker, Manuela Zucknick, Arefeh Rouhi, Anja Weigel, Rainer Claus, Dieter Weichenhan, Barbara Eichhorst, Kirsten Fischer, Michael Hallek, Florian Kuchenbauer, Christoph Plass, Hartmut Döhner, Stephan Stilgenbauer, Peter Lichter, Daniel Mertens
B cell receptor (BCR) signaling is key for survival of chronic lymphocytic leukemia (CLL) cells, and BCR signaling inhibitors are clinically active. However, relapse and resistance to treatment require novel treatment options. In order to detect novel candidate therapeutic targets, we performed a genome-wide DNA methylation screen with custom arrays and identified aberrant promoter DNA methylation in 2192 genes. The transcription factor NFATC1 that is a downstream effector of BCR signaling was among the top hypomethylated genes and was concomitantly transcriptionally upregulated in CLL...
September 18, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28915690/efficacy-and-safety-of-a-reduced-calcineurin-inhibitor-dose-combined-with-mycophenolate-mofetil-in-liver-transplant-patients-with-chronic-renal-dysfunction
#9
Pusen Wang, Weitao Que, Hao Li, Lvnan Yan, Zhiren Fu, Qifa Ye, Guihua Chen, Kefeng Dou, Shichun Lu, Zhanyu Yang, Zhijun Zhu, Zhihai Peng, Lin Zhong
Calcineurin inhibitors (CNIs) are frequently given at a reduced dose in combination with mycophenolate mofetil (MMF) to avoid nephrotoxicity, but the optimal reduction in CNI dose has not been established. In this prospective, open-label, multicenter study, liver transplant recipients with chronic renal dysfunction who were administered a CNI-based immunosuppressive regimen were included in the intent-to-treat (ITT) population. The primary endpoint was declination in renal function, which was defined as a ≥ 20% decrease in the glomerular filtration rate during the year following regimen adjustment...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912999/tacrolimus-aggravated-tube-feeding-syndrome-with-acute-renal-failure-in-a-pediatric-liver-transplant-recipient
#10
R Kula, M Melter, J Kunkel, C Dörfler, S Alikadic, B Knoppke, R Zant
Acute renal failure can be caused by calcineurin inhibitors (CNIs), due to arteriolopathy and altered tubular function. Within this context, we present the case of a 14-month-old liver transplant recipient who suffered an acute polyuric renal failure during a short episode of hypercaloric feeding. In our case, CNI-induced distal RTA led to nephrocalcinosis and therefore to secondary nephrogenic diabetes insipidus. The diet with high renal solute load consequently resulted in an acute polyuric renal failure with severe hypernatremic dehydration...
2017: Case Reports in Transplantation
https://www.readbyqxmd.com/read/28906028/graft-outcomes-following-diagnosis-of-posttransplant-lymphoproliferative-disease-in-pediatric-kidney-recipients-a-retrospective-study
#11
Nele K Kanzelmeyer, Britta Maecker-Kolhoff, Henriette Zierhut, Christian Lerch, Murielle Verboom, Dieter Haffner, Lars Pape
Data related to graft outcomes following posttransplant lymphoproliferative disease (PTLD) in pediatric kidney transplantation are scarce. Data were analyzed retrospectively from 12 children (8 boys) for three years after diagnosis of PTLD, with a loss of follow-up after 2 years in 2/12. In all cases, intensity of immunosuppressive therapy was reduced, with switch from calcineurin inhibitor to a mammalian target of rapamcyin (mTOR) inhibitor in 6 cases. Nine children were treated with 6 doses of rituximab according to the PED-PTLD-2005 protocol, with additional treatment in one child as per protocol...
September 14, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28904428/collapsing-glomerulopathy-a-troublemaker-for-the-renal-allograft-lessons-learnt
#12
K V Kanodia, A V Vanikar, L K Nigam, R D Patel, K S Suthar, H V Patel, H L Trivedi
Collapsing glomerulopathy (CG) is a well-recognized distinct morphological pattern of proliferative parenchymal injury leading to rapid graft failure. We conducted a single-center retrospective study to evaluate the prevalence, clinicopathological features, and prognosis of CG in renal transplant recepient. We analyzed 2518 renal allograft biopsies performed from 2007 to 2015 and correlated their clinicopathological features. The prevalence of CG was 0.83% (21 out of 2518) of allograft biopsies with a higher prevalence of 1...
September 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28899790/alisporivir-rescues-defective-mitochondrial-respiration-in-duchenne-muscular-dystrophy
#13
Marco Schiavone, Alessandra Zulian, Sara Menazza, Valeria Petronilli, Francesco Argenton, Luciano Merlini, Patrizia Sabatelli, Paolo Bernardi
Duchenne muscular dystrophy (DMD) is a severe muscle disease of known etiology without effective, or generally applicable therapy. Mitochondria are affected by the disease in animal models but whether mitochondrial dysfunction is part of the pathogenesis in patients remains unclear. We show that primary cultures obtained from muscle biopsies of DMD patients display a decrease of the respiratory reserve, a consequence of inappropriate opening of the permeability transition pore (PTP). Treatment with the cyclophilin inhibitor alisporivir - a cyclosporin A derivative that desensitizes the PTP but does not inhibit calcineurin - largely restored the maximal respiratory capacity without affecting basal oxygen consumption in cells from patients, thus reinstating a normal respiratory reserve...
September 9, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28899698/betulinic-acid-derivative-ba5-a-dual-nf-kb-calcineurin-inhibitor-alleviates-experimental-shock-and-delayed-hypersensitivity
#14
Cássio Santana Meira, Renan Fernandes do Espírito Santo, Tatiana Barbosa Dos Santos, Iasmim Diniz Orge, Dahara Keyse Carvalho Silva, Elisalva Teixeira Guimarães, Luciana Souza de Aragão França, José Maria Barbosa-Filho, Diogo Rodrigo Magalhães Moreira, Milena Botelho Pereira Soares
Betulinic acid (BA) is a naturally occurring triterpenoid with several biological properties already described, including immunomodulatory activity. Here we investigated the immunomodulatory activity of eight semi-synthetic amide derivatives of betulinic acid. Screening of derivatives BA1-BA8 led to the identification of compounds with superior immunomodulatory activity than BA on activated macrophages and lymphocytes. BA5, the most potent derivative, inhibited nitric oxide and TNFα production in a concentration-dependent manner, and decreased NF-κB activation in Raw 264...
September 9, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28895956/atopic-dermatitis-skin-care-and-topical-therapies
#15
David M Fleischer, Jeremy Udkoff, Jenna Borok, Adam Friedman, Noreen Nicol, Jeffrey Bienstock, Peter Lio, Megha M Tollefson, Lawrence F Eichenfield
Atopic dermatitis (AD) pathogenesis is strongly influenced by Type 2 innate lymphoid cell and T-helper cell type 2 lymphocyte-driven inflammation and skin barrier dysfunction. AD therapies attempt to correct this pathology, and guidelines suggest suggest basics of AD therapy, which include repair of the skin barrier through bathing practices and moisturizers, infection control, and further lifestyle modifications to avoid and reduce AD triggers.While some patients' AD may be controlled using these measures, inflammatory eczema including acute flares and maintenance therapy in more severe patients are treated with topical pharmacologic agents such as topical corticosteroids, topical calcineurin inhibitors, and, more recently, topical PDE-4 inhibitors...
September 2017: Seminars in Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28890387/peptides-derived-from-transcription-factor-eb-bind-to-calcineurin-at-a-similar-region-as-the-nfat-type-motif
#16
Ruiwen Song, Jing Li, Jin Zhang, Lu Wang, Li Tong, Ping Wang, Huan Yang, Qun Wei, Huaibin Cai, Jing Luo
Calcineurin (CN) is involved in many physiological processes and interacts with multiple substrates. Most of the substrates contain similar motifs recognized by CN. Recent studies revealed a new CN substrate, transcription factor EB (TFEB), which is involved in autophagy. We showed that a 15-mer QSYLENPTSYHLQQS peptide from TFEB (TFEB-YLENP) bound to CN. When the TFEB-YLENP peptide was changed to YLAVP, its affinity for CN increased and it had stronger CN inhibitory activity. Molecular dynamics simulations revealed that the TFEB-YLENP peptide has the same docking sites in CN as the 15-mer DQYLAVPQHPYQWAK motif of the nuclear factor of activated T cells, cytoplasmic 1 (NFATc1-YLAVP)...
September 7, 2017: Biochimie
https://www.readbyqxmd.com/read/28889715/-simultaneous-hepatorenal-transplantation-from-a-brain-dead-donor-for-graft-dysfunction-and-renal-insufficiency-in-a-liver-transplant-recipient-a-case-report
#17
Hideaki Takada, Takashi Kobayashi, Kohei Ogawa, Hitomi Miyata, Atsuro Sawada, Shusuke Akamatsu, Hiromitsu Negoro, Ryoichi Saito, Naoki Terada, Toshinari Yamasaki, Takahiro Inoue, Yuki Teramoto, Shinsuke Shibuya, Hironori Haga, Toshimi Kaido, Shinji Uemoto, Osamu Ogawa
We report a case of lethal hepatorenal insufficiency in a 52-year-old man who received successful simultaneous hepatorenal transplantation from a deceased donor. The patient had undergone live-donor liver transplantation for type-C hepatitis and liver cirrhosis 11 years before he developed graft liver dysfunction due to recurrent viral hepatitis and cirrhosis. At that instance, he also developed end-stage renal dysfunction due to calcineurin inhibitor nephropathy and hepatorenal syndrome. Although he needed three open hemostases and abundant blood transfusion, he was withdrawn from continuous hemodiafiltration on the 55th day and discharged from the hospital on the 272nd day postoperatively...
August 2017: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/28882776/immunosuppressant-medication-induced-lower-extremity-pain-after-combined-liver-and-kidney-transplant-a-case-report
#18
Thanzeela Kausar Mohideen, Hong Wu
Calcineurin inhibitors are imperative in the success of a transplanted organ. However, these immunosuppressants can lead to a rare complication known as calcineurin inhibitor induced pain syndrome (CIPS), which may not be recognized early and managed appropriately. We present a case of a 35-year-old female who underwent a combined liver/kidney transplant and developed lower extremity pain while being maintained on tacrolimus. This case illustrates a patient with previously reported characteristic clinical features of CIPS in addition to uncharacteristic neuropathic symptoms and imaging findings...
September 4, 2017: PM & R: the Journal of Injury, Function, and Rehabilitation
https://www.readbyqxmd.com/read/28882100/low-dose-cyclosporine-in-treatment-of-membranous-nephropathy-with-nephrotic-syndrome-effectiveness-and-renal-safety
#19
Xiaojuan Yu, Lin Ruan, Zhen Qu, Zhao Cui, Yimiao Zhang, Xin Wang, Liqiang Meng, Xiaojing Liu, Fang Wang, Ying Zhang, Gang Liu, Li Yang
BACKGROUND: To observe effectiveness and renal safety of long-term low-dose cyclosporine in idiopathic membranous nephropathy (IMN). METHODS: Sixty-eight patients were enrolled in this prospective cohort study. Renal endpoint was defined as a decrease in eGFR ≥50% from baseline and a development of eGFR ≤60 ml/min/1.73m(2). RESULTS: A cyclosporine dose of 2.0 ± 0.5 mg/kg/d and a prednisone of 0.3 ± 0.2 mg/kg/d were prescribed...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28879428/difficult-to-treat-idiopathic-nephrotic-syndrome-established-drugs-open-questions-and-future-options
#20
REVIEW
Markus J Kemper, Lisa Valentin, Michael van Husen
The idiopathic nephrotic syndrome in childhood can be classified according to the International Study of Kidney Disease in Children (ISKDC) based on the response to steroids. Typically, steroid-sensitive nephrotic syndrome (SSNS) is characterised by minimal changes in disease (MCD) histology, whereas in steroid-resistant nephrotic syndrome (SRNS) focal segmental glomerulosclerosis (FSGS) is the most prevalent lesion. Patients with SSNS may develop frequent relapses and/or steroid dependency, which can be difficult to treat...
September 6, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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