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Acute renal allograft rejection

G Varela-Fascinetto, C Benchimol, R Reyes-Acevedo, M Genevray, D Bradley, J Ives, H T Silva
This multicenter, open-label study evaluated the tolerability of extended prophylaxis with valganciclovir in pediatric kidney transplant recipients at risk of CMV disease. Fifty-six patients aged 4 months to 16 years received once-daily valganciclovir oral solution and/or tablets, dosed by BSA and renal function, for up to 200 days. The most common AEs on treatment were upper respiratory tract infection (33.9%), urinary tract infection (33.9%), diarrhea (32.1%), leukopenia (25.0%), neutropenia (23.2%), and headache (21...
October 17, 2016: Pediatric Transplantation
Catherine Forconi, Philippe Gatault, Elodie Miquelestorena-Standley, Johan Noble, Sally Al-Hajj, Romain Guillemain, Marc Stern, Thomas Hoffmann, Louis Prat, Caroline Suberbielle, Emeline Masson, Anne Cesbron-Gautier, Catherine Gaudy-Graffin, Alain Goudeau, Gilles Thibault, Fabrice Ivanes, Roseline Guibon, Ihab Kazma, Yvon Lebranchu, Matthias Büchler, Antoine Magnan, Jean-Michel Halimi, Christophe Baron
BACKGROUND: Cytomegalovirus (CMV) has a role in chronic rejection and graft loss in kidney transplant (KTx) and lung transplant (LTx) recipients. In addition, donor CMV seropositivity is an independent risk factor for renal graft loss. The anti-CMV response might modulate this risk. Expression of programmed cell death 1 (PD-1), a receptor involved in viral-specific T-cell exhaustion, is influenced by a single nucleotide polymorphism called PD-1.3 (wild-type allele G, variant allele A)...
August 26, 2016: Journal of Heart and Lung Transplantation
Ahmer M Hameed, Henry C Pleass, Germaine Wong, Wayne J Hawthorne
BACKGROUND: The two main options for renal allograft preservation are static cold storage (CS) and machine perfusion (MP). There has been considerably increased interest in MP preservation of kidneys, however conflicting evidence regarding its efficacy and associated costs have impacted its scale of clinical uptake. Additionally, there is no clear consensus regarding oxygenation, and hypo- or normothermia, in conjunction with MP, and its mechanisms of action are also debated. The primary aims of this article were to elucidate the benefits of MP preservation with and without oxygenation, and/or under normothermic conditions, when compared with CS prior to deceased donor kidney transplantation...
October 2016: Medicine (Baltimore)
David Wojciechowski, Flavio Vincenti
Kidney transplantation immunosuppression relies on a calcineurin inhibitor backbone. Calcineurin inhibitors have reduced early-acute rejection rates but failed to improve long-term allograft survival. Their nephrotoxicity has shifted the focus of investigation to calcineurin inhibitor-free regimens. Costimulation blockade with belatacept, a second generation, higher avidity variant of CTLA4-Ig, has emerged as part of a calcineurin inhibitor-free regimen. Belatacept has demonstrated superior glomerular filtration rate compared with calcineurin inhibitors albeit with an increased risk of early and histologically severe rejection...
September 2016: Advances in Chronic Kidney Disease
F Toth, G Zadori, R Fedor, L Illesy, M Szabo-Pap, Z Kanyari, D A Kovacs, L Asztalos, B Nemes
INTRODUCTION: Approximately 10% of renal allografts fail during the first year after kidney transplantation (KT) and 3%-5% thereafter yearly. The indication and timing of allograft nephrectomy (AN) is still uncertain in some cases. The aim of this study was to reveal the ratio, etiology, and complications of AN at our center. MATERIAL AND METHODS: This is a retrospective study of all patients who underwent KT at our center between January 1, 2004 and December 31, 2014...
September 2016: Transplantation Proceedings
Anne Tsampalieros, Greg A Knoll, Amber O Molnar, Nicholas Fergusson, Dean A Fergusson
BACKGROUND: A number of corticosteroid minimization and avoidance protocols for post-solid organ transplant have been developed. The study objective was to examine the effect of corticosteroid withdrawal/avoidance on growth and safety parameters in pediatric solid organ transplant recipients. METHODS: A systematic review using Medline and Embase was performed. All randomized controlled trials (RCT) and observational studies comparing corticosteroid withdrawal/avoidance to controls receiving corticosteroids in pediatric transplant recipients which reported growth as change in height or final height were included...
July 12, 2016: Transplantation
Omar Wever-Pinzon, Leah B Edwards, David O Taylor, Abdallah G Kfoury, Stavros G Drakos, Craig H Selzman, James C Fang, Lars H Lund, Josef Stehlik
BACKGROUND: Survival beyond 1 year after heart transplantation has remained without significant improvement for the last 2 decades. A more individualized approach to post-transplant care could result in a reduction of long-term mortality. Although recipient age has been associated with an increased incidence of certain post-transplant morbidities, its effect on cause-specific mortality has not been established. METHODS: We analyzed overall and cause-specific mortality of heart transplant recipients registered in the International Society for Heart and Lung Transplantation Registry between 1995 and 2011...
August 20, 2016: Journal of Heart and Lung Transplantation
Xiaoguang Xu, Haiyan Huang, Qiang Wang, Ming Cai, Yeyong Qian, Yong Han, Xinying Wang, Yu Gao, Ming Yuan, Liang Xu, Chen Yao, Li Xiao, Bingyi Shi
PURPOSE: IFN-γ is a protypical proinflammatory cytokine that plays a central role in inflammation and acute graft rejection. Accumulating evidence indicates that IFN-γ can exert previously unexpected immunoregulatory activities. However, little is known about the role of IFN-γ secreted by Th1-like regulatory T cells in human kidney transplantation. METHODS: To determine the function of IFN-γ in acute T cell-mediated renal allograft rejection (ACR), we examined serum cytokine expression profiles in ACR patients by human cytokine multiplex immunoassay and analyzed the cellular origins of IFN-γ in peripheral blood and renal allograft biopsies from ACR cases and controls by flow cytometry and immunohistochemistry, respectively...
September 19, 2016: Immunobiology
Sourabh Chand, David Atkinson, Clare Collins, David Briggs, Simon Ball, Adnan Sharif, Kassiani Skordilis, Bindu Vydianath, Desley Neil, Richard Borrows
BACKGROUND: Causes of "true" late kidney allograft failure remain unclear as study selection bias and limited follow-up risk incomplete representation of the spectrum. METHODS: We evaluated all unselected graft failures from 2008-2014 (n = 171; 0-36 years post-transplantation) by contemporary classification of indication biopsies "proximate" to failure, DSA assessment, clinical and biochemical data. RESULTS: The spectrum of graft failure changed markedly depending on the timing of allograft failure...
2016: PloS One
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
Katja Hueper, Marcel Gutberlet, Jan Hinrich Bräsen, Mi-Sun Jang, Anja Thorenz, Rongjun Chen, Barbara Hertel, Amelie Barrmeyer, Martina Schmidbauer, Martin Meier, Sibylle von Vietinghoff, Abedalrazag Khalifa, Dagmar Hartung, Hermann Haller, Frank Wacker, Song Rong, Faikah Gueler
BACKGROUND: Kidney transplantation (ktx) in mice is used to learn about rejection and to develop new treatment strategies. Past studies have mainly been based on histological or molecular biological methods. Imaging techniques to monitor allograft pathology have rarely been used. METHODS: Here we investigated mice after isogenic and allogenic ktx over time with functional MRI with diffusion-weighted imaging (DWI) and mapping of T2-relaxation time (T2-mapping) to assess graft inflammation and edema formation...
2016: PloS One
Takeshi Maehana, Toshiaki Tanaka, Hiroshi Kitamura, Nobuyuki Fukuzawa, Hideki Ishida, Hiroshi Harada, Kazunari Tanabe, Naoya Masumori
BACKGROUND: Heat shock protein 90 (HSP90), a molecular chaperone associated with the activation of client proteins, was recently reported to play an important role in immunologic reactions. To date, the role of HSP90 in solid organ transplantations has remained unknown. The aim of this study was to evaluate the relationship between serum HSP90α levels and acute allograft rejection after organ and tissue transplantation using serum samples from kidney allograft recipients, an in vitro antibody-mediated rejection model, and a murine skin transplantation...
2016: PloS One
L Song, A Ma, H Dun, Y Hu, Y Fujii, F Kinugasa, S Oshima, Y Higashi, P Daloze, H Chen
Belatacept is the first costimulatory blockade agent approved for maintenance immunosuppression in kidney transplant recipients. Clinical results have indicated that belatacept is associated with superior renal function and improved metabolic profile. However, higher incidence of acute rejection and PTLD are the shortcomings of this agent. In this study, ASP2409, a new CTLA4-Ig possessing 14-fold higher in vitro CD86 binding affinity than belatacept, was tested for renal allograft survival in cynomolgus monkeys...
September 6, 2016: American Journal of Transplantation
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
Daniela Cristina Dos Santos, Niels Olsen Saraiva Camara, Daisa Silva Ribeiro David, Denise Maria Avancini Costa Malheiros
BACKGROUND: The study investigated whether immunohistochemical features of interstitial and glomerular CD56 and CD16 infiltrates - NK cells markers - could be associated with microcirculation injury scores - peritubular capillaritis (ptc) and glomerulitis (g) - and graft survival. METHODS: The research analyzed the immunohistochemical pattern of CD56 and CD16 in interstitial and glomerular compartments of biopsies for-cause biopsies from 59 recipients diagnosed with acute rejection (mean = 135...
August 18, 2016: Nephrology
Hans A Schlößer, Martin Thelen, Georg Dieplinger, Anke von Bergwelt-Baildon, Maria Garcia-Marquez, Sabrina Reuter, Alexander Shimabukuro-Vornhagen, Kerstin Wennhold, Natalie Haustein, Denise Buchner, Nadine Heiermann, Robert Kleinert, Roger Wahba, Vanessa Ditt, Christine Kurschat, Tülay Cingöz, Jan Becker, Dirk L Stippel, Michael von Bergwelt-Baildon
Immunosuppressive strategies applied in renal transplantation traditionally focus on T-cell inhibition. B cells were mainly examined in the context of antibody-mediated rejection, whereas the impact of antibody-independent B-cell functions has only recently entered the field of transplantation. Similar to T cells distinct B-cell subsets can enhance or inhibit immune responses. In this study, we prospectively analyzed the evolution of B-cell subsets in peripheral blood of AB0-compatible (n=27) and AB0-incompatible (n=10) renal transplant recipients...
August 16, 2016: American Journal of Transplantation
Jennifer L McRae, Joanne Sj Chia, Sandra A Pommey, Karen M Dwyer
AIM: Regulatory T cells (Treg) are important in mediating immune tolerance and outcomes of allotransplantation. CD4(+) CD25(+) CD39(+) co-expression identifies memory Treg; CD4(+) CD25(-) CD39(+) memory T effectors. We sought to determine CD4(+) CD25(+/-) CD39(+) expression from the peripheral blood of patients with end stage renal failure, following transplantation and during episodes of acute cellular rejection. METHODS: CD4(+) T cells were isolated from peripheral blood leucocytes and analysed for CD25 and CD39 expression by flow cytometry...
August 12, 2016: Nephrology
David Wojciechowski, Flavio Vincenti
PURPOSE OF REVIEW: The review will focus on the impact and current status of costimulatory blockade in renal transplantation. RECENT FINDINGS: The mainstay of immunosuppression in kidney transplantation is calcineurin inhibitors (CNIs) which have reduced acute rejection rates but failed to improve long-term allograft survival. Their cardiometabolic side-effects and nephrotoxicity have shifted the focus of investigation to CNI-free regimens. Costimulation blockade with belatacept, a second generation, higher avidity variant of cytotoxic T-lymphocyte associated protein 4 has emerged as part of a CNI-free regimen...
November 2016: Current Opinion in Nephrology and Hypertension
Helio Tedesco-Silva, V Ram Peddi, Ana Sánchez-Fructuoso, Brad A Marder, Graeme R Russ, Fritz Diekmann, Alison Flynn, Carolyn M Hahn, Huihua Li, Michael A Tortorici, Seth L Schulman
UNLABELLED: Calcineurin inhibitor-associated nephrotoxicity and other adverse events have prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney transplant recipients. METHODS: This open-label, randomized, multinational study evaluated the effect of planned transition from tacrolimus to sirolimus on kidney function in renal allograft recipients. Patients received tacrolimus-based immunosuppression and then were randomized 3 to 5 months posttransplantation to transition to sirolimus or continue tacrolimus...
April 2016: Transplantation Direct
Anneke Brand
Most adverse blood transfusion (BT) events are immune-mediated and in the majority of severe reactions antibodies can be identified as causal factors. Alloimmunization not only causes symptomatic reactions, transfused cells can also be (silently) destroyed. Immunization by BT can contribute to hemolytic disease of the newborn as well as to allograft rejection after transplantation. Reversely, pregnancy and transplantation may evoke immunity hampering transfusion therapy. Besides causing mortality and morbidity, alloimmunization has a huge economic impact...
July 2016: La Presse Médicale
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