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Eculizumab transplant

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https://www.readbyqxmd.com/read/29920784/eculizumab-for-transplant-associated-thrombotic-microangiopathy-in-adult-allogeneic-stem-cell-transplant-recipients
#1
Joslyn Rudoni, Anna Jan, Chitra Hosing, Fleur Aung, Jason Yeh
OBJECTIVE: To evaluate response rates and survival in adults with transplant-associated thrombotic microangiopathy (TA-TMA) after allogeneic hematopoietic stem cell transplantation (HSCT) who were treated with eculizumab (ECU). METHODS: Patients were identified retrospectively and data collected through HSCT and pharmacy databases. RESULTS: Ten patients with TA-TMA after allogeneic HSCT were treated with ECU between 2013 and 2016. TA-TMA was diagnosed at a median of 93 days post-HSCT...
June 19, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29897310/an-unusual-pattern-of-peritubular-capillary-injury-involving-apoptosis-in-a-renal-transplant-patient
#2
John K Brealey, John Cassidy, Jim Manavis
Microvascular injury is an important factor in renal allograft survival. Repeated episodes of endothelial injury from chronic antibody-mediated rejection typically manifest at the ultrastructural level as circumferential multilayering of remodeled glomerular basement membrane material and peritubular capillary basal lamina. In contrast to this typical pattern of microvascular injury, a renal transplantation case is presented in which focally dilated and multilayered segments of peritubular capillary basal lamina bearing lipid droplets were interspersed with ultrastructurally normal unilayered segments of basal lamina devoid of lipid droplets...
June 13, 2018: Ultrastructural Pathology
https://www.readbyqxmd.com/read/29870459/novel-approaches-to-block-complement
#3
Georg A Böhmig, Markus Wahrmann, Farsad Eskandary, Lionel Rostaing
The complement system may contribute in many ways to transplant injury, being a promising target for specific therapeutic interventions. There is evidence that the monoclonal anti-C5 antibody eculizumab is effective in the prevention and treatment of early antibody-mediated rejection (ABMR), but terminal complement blockade might be of limited efficiency in chronic rejection. Given the diversity of immunological events triggered by activation steps upstream to C5, in particular, opsonin and anaphylatoxin formation through C3 cleavage, one may argue that, in the specific context of ABMR, inhibition of antibody-triggered classical pathway (CP) activation might be beneficial...
June 4, 2018: Transplantation
https://www.readbyqxmd.com/read/29858281/c5b9-formation-on-endothelial-cells-reflects-complement-defects-among-patients-with-renal-thrombotic-microangiopathy-and-severe-hypertension
#4
Sjoerd A M E G Timmermans, Myrurgia A Abdul-Hamid, Judith Potjewijd, Ruud O M F I H Theunissen, Jan G M C Damoiseaux, Chris P Reutelingsperger, Pieter van Paassen
Background Severe hypertension can induce thrombotic microangiopathy (TMA) in the renal vasculature, the occurrence of which has been linked to mechanical stress to the endothelium. Complement defects may be the culprit of disease in patients who present with severe renal disease and often progress to ESRD, despite BP control. Methods We studied a well defined cohort of 17 patients with hypertension-associated TMA to define the prevalence of complement defects by a specific ex vivo serum-based microvascular endothelial cell assay...
June 1, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29778558/successful-kidney-transplant-with-eculizumab-thymoglobulin-and-belatacept-therapy-in-a-highly-sensitised-patient-with-atypical-haemolytic-uraemic-syndrome-due-to-factor-h-mutation
#5
John Fredy Nieto-Ríos, Mónica Zuluaga-Quintero, Diana Carolina Bello-Márquez, Arbey Aristizabal-Alzate, Catalina Ocampo-Kohn, Lina María Serna-Higuita, Lina Arias, Gustavo Zuluaga-Valencia
Atypical haemolytic uremic syndrome is a disease caused by complement regulation abnormalities that generally progresses to chronic end-stage renal disease with a high rate of recurrence in kidney transplantation and a high risk of graft loss. Anti-complement therapy has improved the prognosis of these patients, achieving disease remission in most cases, increasing the likelihood of a successful kidney transplant and increasing patient and graft survival. Drugs with low risk of induction of thrombotic microangiopathies such as belatacept and mycophenolate have also been used with satisfactory results...
May 16, 2018: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/29732228/de-novo-atypical-haemolytic-uremic-syndrome-after-kidney-transplantation
#6
Arnaud Devresse, Martine de Meyer, Selda Aydin, Karin Dahan, Nada Kanaan
De novo thrombotic microangiopathy (TMA) can occur after kidney transplantation. An abnormality of the alternative pathway of complement must be suspected and searched for, even in presence of a secondary cause. We report the case of a 23-year-old female patient who was transplanted with a kidney from her mother for end-stage renal disease secondary to Hinman syndrome. Early after transplantation, she presented with 2 episodes of severe pyelonephritis, associated with acute kidney dysfunction and biological and histological features of TMA...
2018: Case Reports in Nephrology
https://www.readbyqxmd.com/read/29724174/eculizumab-as-salvage-therapy-for-recurrent-monoclonal-gammopathy-induced-c3-glomerulopathy-in-a-kidney-allograft
#7
Philipp Moog, Philipp J Jost, Maike Büttner-Herold
BACKGROUND: Monoclonal gammopathy causes several kinds of renal pathology. A rare and special form is monoclonal gammopathy-induced C3 glomerulopathy (MG-C3G). Like idiopathic C3G, MG-C3G frequently leads to end-stage renal disease. MG-C3G frequently recurs after renal transplantation, leading to graft failure in most of the patients. While there is some evidence for successful treatment of recurrent idiopathic C3 glomerulopathy with eculizumab after renal transplantation, nothing is known about its efficacy in the setting of recurrent MG-C3G...
May 3, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29699703/where-are-we-with-haemolytic-uremic-syndrome
#8
REVIEW
Teresa Cavero, Marina Alonso
Haemolytic uremic syndrome (HUS) is characterised by microangiopathic haemolytic anaemia with acute kidney injury. It is currently classified into two main categories: Shiga-toxin producing E. coli-hemolytic uremic syndrome (STEC-HUS) and atypical haemolytic uremic syndrome (aHUS). Endothelial cell damage is the common pathway in HUS to developing thrombotic microangiopathy. Atypical HUS includes primary, secondary and aHUS due to metabolic diseases. In the majority of aHUS cases, hyperactivity of the alternative complement pathway plays a central role...
April 23, 2018: Medicina Clínica
https://www.readbyqxmd.com/read/29674658/high-dose-carboplatin-etoposide-melphalan-increases-risk-of-thrombotic-microangiopathy-and-organ-injury-after-autologous-stem-cell-transplantation-in-patients-with-neuroblastoma
#9
Sonata Jodele, Christopher E Dandoy, Kasiani Myers, Gregory Wallace, Adam Lane, Ashley Teusink-Cross, Brian Weiss, Stella M Davies
Transplant-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication of hematopoietic cell transplant that can result in multi-organ failure (MOF). Patients undergoing high-dose chemotherapy with autologous stem cell transplant (aHCT) for neuroblastoma require good organ function to receive post-transplant radiation and immunotherapy. We examined TA-TMA incidence and transplant outcomes in patients with neuroblastoma receiving different transplant preparative regimens. Sixty patients underwent aHCT using high-dose chemotherapy: 41 patients received carboplatin/etoposide/melphalan (CEM), 13 patients busulfan/melphalan (Bu/Mel) and six patients received tandem transplant (cyclophosphamide/thiotepa and CEM)...
April 19, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29661469/successful-7-year-eculizumab-treatment-of-plasmapheresis-resistant-recurrent-atypical-hemolytic-uremic-syndrome-due-to-complement-factor-h-hybrid-gene-a-case-report
#10
K Vondrák, T Seeman
Atypical hemolytic-uremic syndrome (aHUS) is an extremely rare disease, and up to 70% of the patients have a genetic mutation in the encoding components of complement activation or anti-complement factor H autoantibodies. The risk of recurrence after kidney transplantation is 10% to 80%. Eculizumab, a monoclonal antibody that binds complement protein C5, has shown to be highly effective in patients with aHUS; however, there are only few reports on the efficacy and safety of long-term eculizumab treatment in children with recurrent aHUS...
April 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29659362/-recurrent-atypical-hemolytic-uremic-syndrome-after-renal-transplantation-treatment-with-eculizumab
#11
Ana B Latzke, Pehuén Fernández, Carlos Chiurchiu, Daniela Sarmantano, Javier De Arteaga, Walter Douthat, Jorge De la Fuente
Atypical hemolytic uremic syndrome (aHUS) is a rare entity. It is characterized by a thrombotic microangiopathy (nonimmune hemolytic anemia, thrombocytopenia, and acute renal failure), with a typical histopathology of thickening of capillary and arteriolar walls and an obstructive thrombosis of the vascular lumen. The syndrome is produced by a genetic or acquired deregulation of the alternative pathway of the complement system, with high rates of end stage renal disease, post-transplant recurrence, and high mortality...
2018: Medicina
https://www.readbyqxmd.com/read/29657196/atypical-hemolytic-uremic-syndrome-a-monocentric-adult-tunisian-study-and-review-of-literature
#12
R Kherder-Elfekih, M Hajji, L Ben Fatma, H Jebali, I Mami, W Smaoui, M Krid, L Rais, S Beji, K Zouaghi, M Sellami-Kallel
Atypical hemolytic uremic syndrome (aHUS) is characterized by microvascular thrombosis resulting in thrombocytopenia, hemolytic anemia, and multiorgan dysfunction. It is associated with genetic or acquired disorders of regulatory components of the complement system. For our study, we collected data from 16 patients diagnosed with aHUS between January 2010 and January 2014. The mean age was 33.6 years. The female-to-male ratio was 3. The median follow-up duration was 27 ± 3.5 months. The most common clinical presentation was hypertension...
March 2018: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/29521880/acute-antibody-mediated-rejection-one-week-after-lung-transplantation-successfully-treated-with-eculizumab-intravenous-immunoglobulins-and-rituximab
#13
Yannick D Muller, John-David Aubert, Julien Vionnet, Samuel Rotman, Salima Sadallah, Vincent Aubert, Manuel Pascual
No abstract text is available yet for this article.
March 8, 2018: Transplantation
https://www.readbyqxmd.com/read/29417722/is-there-a-case-for-eculizumab-for-pediatric-renal-transplantation
#14
EDITORIAL
Guido Filler, Christoph Licht, Shih-Han Susan Huang
No abstract text is available yet for this article.
March 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29407333/eculizumab-for-prevention-of-antibody-mediated-rejection-in-blood-group-incompatible-renal-transplantation
#15
P West-Thielke, K Progar, M Campara, N Jasiak, L Gallon, I Tang, M Spaggiari, I Tzvetanov, E Benedetti
Antibody-mediated rejection (AMR) is one of the leading causes of allograft failure especially in patients undergoing ABO-incompatible (ABOi) renal transplantation. We hypothesized that complement inhibition with eculizumab, a C5 inhibitor, would protect against AMR and maintain graft function in ABOi renal transplant recipients. Four patients undergoing living donor kidney transplant from ABOi donors were treated with a 9-week eculizumab course without therapeutic plasma exchange, intravenous immunoglobulin, or splenectomy...
January 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29377474/a-prospective-randomized-controlled-trial-of-eculizumab-to-prevent-ischemia-reperfusion-injury-in-pediatric-kidney-transplantation
#16
Michael Kaabak, Nadeen Babenko, Ron Shapiro, Allan Zokoyev, Olga Dymova, Edward Kim
Ischemia-reperfusion injury has multiple effects on a transplanted allograft, including delayed or impaired graft function, compromised long-term survival, and an association with an increased incidence of rejection. Eculizumab, a monoclonal antibody blocking terminal complement activation, has been postulated to be an effective agent in the prevention or amelioration of IRI. We performed a single-center prospective, randomized controlled trial involving 57 pediatric kidney transplant recipients between 2012 and 2016...
March 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29370420/c3-glomerulonephritis-secondary-to-mutations-in-factors-h-and-i-rapid-recurrence-in-deceased-donor-kidney-transplant-effectively-treated-with-eculizumab
#17
Neetika Garg, Yuzhou Zhang, Anne Nicholson-Weller, Eliyahu V Khankin, Nicolò Ghiringhelli Borsa, Nicole C Meyer, Susan McDermott, Isaac E Stillman, Helmut G Rennke, Richard J Smith, Martha Pavlakis
Background: C3 glomerulonephritis (C3GN) is caused by alternate complement pathway over-activation. It frequently progresses to end-stage renal disease, recurs in two-thirds of transplants and in half of these cases progresses to allograft loss. There is currently no proven treatment for C3GN. Case Presentation: We describe a family segregating pathogenic alleles of complement factor H and I (CFH and CFI). The only member carrying both mutations developed C3GN. Prolonged delayed graft function after deceased donor transplantation, heavy proteinuria and isolated C3 hypocomplementemia prompted an allograft biopsy confirming diagnosis of recurrent C3GN...
January 23, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29322327/combined-and-sequential-liver-kidney-transplantation-in-children
#18
Ryszard Grenda, Piotr Kaliciński
Combined and sequential liver-kidney transplantation (CLKT and SLKT) is a definitive treatment in children with end-stage organ failure. There are two major indications: - terminal insufficiency of both organs, or - need for transplanting new liver as a source of lacking enzyme or specific regulator of the immune system in a patient with renal failure. A third (uncommon) option is secondary end-stage renal failure in liver transplant recipients. These three clinical settings use distinct qualification algorithms...
January 10, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29315141/the-treatment-of-antibody-mediated-rejection-in-kidney-transplantation-an-updated-systematic-review-and-meta-analysis
#19
Susan S Wan, Tracey D Ying, Kate Wyburn, Darren M Roberts, Melanie Wyld, Steven J Chadban
BACKGROUND: Current treatments for antibody-mediated rejection (AMR) in kidney transplantation are based on low-quality data from a small number of controlled trials. Novel agents targeting B cells, plasma cells, and the complement system have featured in recent studies of AMR. METHODS: We conducted a systematic review and meta-analysis of controlled trials in kidney transplant recipients using Medline, EMBASE, and CENTRAL from inception to February 2017. RESULTS: Of 14 380 citations, we identified 21 studies, including 10 randomized controlled trials, involving 751 participants...
April 2018: Transplantation
https://www.readbyqxmd.com/read/29296809/in-vitro-evidence-of-complement-activation-in-transplantation-associated-thrombotic-microangiopathy
#20
Seth J Rotz, Nathan Luebbering, Bradley P Dixon, Eleni Gavriilaki, Robert A Brodsky, Christopher E Dandoy, Sonata Jodele, Stella M Davies
Transplantation-associated thrombotic microangiopathy is associated with complement activation in vitro.This data further supports the use of eculizumab for the treatment of patients with TA-TMA.
September 12, 2017: Blood Advances
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