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https://www.readbyqxmd.com/read/29042454/complement-activating-anti-hla-antibodies-in-kidney-transplantation-allograft-gene-expression-profiling-and-response-to-treatment
#1
Carmen Lefaucheur, Denis Viglietti, Luis G Hidalgo, Lloyd E Ratner, Serena M Bagnasco, Ibrahim Batal, Olivier Aubert, Babak J Orandi, Federico Oppenheimer, Oriol Bestard, Paolo Rigotti, Anna V Reisaeter, Nassim Kamar, Yvon Lebranchu, Jean-Paul Duong Van Huyen, Patrick Bruneval, Denis Glotz, Christophe Legendre, Jean-Philippe Empana, Xavier Jouven, Dorry L Segev, Robert A Montgomery, Adriana Zeevi, Philip F Halloran, Alexandre Loupy
Complement-activating anti-HLA donor-specific antibodies (DSAs) are associated with impaired kidney transplant outcome; however, whether these antibodies induce a specific rejection phenotype and influence response to therapy remains undetermined. We prospectively screened 931 kidney recipients for complement-activating DSAs and used histopathology, immunostaining, and allograft gene expression to assess rejection phenotypes. Effector cells were evaluated using in vitro human cell cultures. Additionally, we assessed the effect of complement inhibition on kidney allograft rejection phenotype and the clinical response to complement inhibition in 116 independent kidney recipients with DSAs at transplant receiving rejection prophylaxis with eculizumab or standard of care (plasma exchange and intravenous Ig) at ten international centers...
October 17, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28993886/thrombotic-microangiopathy-following-haematopoietic-stem-cell-transplant
#2
Eleanor G Seaby, Rodney D Gilbert
Thrombotic microangiopathy is a potentially lethal complication of haematopoietic stem cell (bone marrow) transplantation. The pathophysiology is incompletely understood, although endothelial damage appears to be central. Platelet activation, neutrophil extracellular traps and complement activation appear to play key roles. Diagnosis may be difficult and universally accepted diagnostic criteria are not available. Treatment remains controversial. In some cases, withdrawal of calcineurin inhibitors is adequate...
October 9, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28991129/a-heterozygous-cfhr3-cfhr1-gene-deletion-in-a-pediatric-patient-with-transplant-associated-thrombotic-microangiopathy-who-was-treated-with-eculizumab
#3
Akifumi Nozawa, Michio Ozeki, Tomohiro Hori, Norio Kawamoto, Masahiro Hirayama, Eiichi Azuma, Toshiyuki Fukao
Complement system dysregulation, such as complement Factor H (CFH) autoantibodies and deletions in CFH-related (CFHR) genes 3 and 1, might cause transplant-associated thrombotic microangiopathy (TA-TMA). The use of eculizumab, a terminal complement inhibitor, could be a targeted therapy for TA-TMA. We report a 1-year-old girl who developed TA-TMA, just after autologous peripheral blood stem cell transplantation in neuroblastoma therapy. Eculizumab improved TA-TMA. Investigation for the complement alternative pathway showed a heterozygous CFHR3-CFHR1 gene deletion, which is involved in complement activation...
October 4, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28947259/-hemolytic-and-uremic-syndrome-and-related-thrombotic-microangiopathies-treatment-and-prognosis
#4
C Rafat, P Coppo, F Fakhouri, V Frémeaux-Bacchi, C Loirat, J Zuber, E Rondeau
Major achievements in the understanding of thrombotic microangiopathies (TMA) have not only resulted in a reclassification of TMA but most of all they have culminated in the design of new treatments and have enabled clinicians to better delineate their prognosis. Recent multicenter studies have improved our understanding of the prognosis of atypical hemolytic and uremic syndromes (aHUS). More specifically, they have highlighted the role of genetic testing on predicting the recurrence of aHUS, the risk of chronic kidney disease and the recurrence following kidney transplantation...
September 22, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28946961/secondary-thrombotic-microangiopathy-and-eculizumab-a-reasonable-therapeutic-option
#5
Elena Román, Santiago Mendizábal, Isidro Jarque, Javier de la Rubia, Amparo Sempere, Enrique Morales, Manuel Praga, Ana Ávila, José Luis Górriz
Understanding the role of the complement system in the pathogenesis of atypical haemolytic uraemic syndrome and other thrombotic microangiopathies (TMA) has led to the use of anti-complement therapy with eculizumab in these diseases, in addition to its original use in patients with paroxysmal nocturnal haemoglobinuria andatypical haemolytic uraemic syndrome. Scientific evidence shows that both primary and secondary TMAs with underlying complement activation are closely related. For this reasons, control over the complement system is a therapeutic target...
September 2017: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/28940540/successful-kidney-transplantation-in-a-patient-with-congenital-thrombotic-thrombocytopenic-purpura-upshaw-schulman-syndrome
#6
Hasan Fattah, Dhiren Kumar, James N George, H Davis Massey, Anne L King, Kenneth D Friedman, Gaurav Gupta
BACKGROUND: Congenital thrombotic thrombocytopenic purpura (TTP) may not be recognized until organ failure related to the microvascular thrombosis occurs. Kidney failure may be the initial presenting clinical feature. Kidney transplantation has been contraindicated because of the assumption that the continuing microvascular thrombosis will cause inevitable graft failure. CASE REPORT: We report a 48-year-old nulliparous woman who presented with end-stage kidney disease that was attributed to hypertension...
September 20, 2017: Transfusion
https://www.readbyqxmd.com/read/28894081/eculizumab-in-renal-transplantation-a-2017-update
#7
Ryszard Grenda, Magdalena Durlik
Despite ongoing progress in renal transplantation, there are still emerging challenges in this field, including consequences of ischemia-reperfusion injury (IRI), pre-existing and produced de novo anti-HLA donor-specific antibodies (DSA), and acute/chronic humoral rejection (AMR), as well as the recurrence of atypical hemolytic-uremic syndrome (aHUS) in genetically predisposed patients. All these conditions are related to the prominent role of the complement system and are deleterious to the fate of the renal graft...
September 12, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28860002/thrombotic-microangiopathy-after-allogeneic-stem-cell-transplantation-a-comparison-of-eculizumab-therapy-and-conventional-therapy
#8
Stephan R Bohl, Florian Kuchenbauer, Stefanie von Harsdorf, Nadine Kloevekorn, Stefan S Schönsteiner, Arefeh Rouhi, Phyllis Schwarzwälder, Hartmut Döhner, Donald Bunjes, Martin Bommer
We report the results of a single-center analysis of a cohort of 39 patients treated between 1997 and 2016 for transplantion-associated thrombotic microangiopathy. We evaluated 2 subgroups of patients: 24 patients treated between 1997 and 2014 who received conventional therapy and 15 patients treated with the complement-inhibiting monoclonal antibody eculizumab between 2014 and 2016. The conventional therapy group was treated predominantly with defibrotide alone or in combination with plasmapheresis or rituximab...
August 30, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28858176/midterm-outcomes-of-12-renal-transplant-recipients-treated-with-eculizumab-to-prevent-atypical-hemolytic-syndrome-recurrence
#9
Charlène Levi, Véronique Frémeaux-Bacchi, Julien Zuber, Marion Rabant, Magali Devriese, Renaud Snanoudj, Anne Scemla, Lucile Amrouche, Arnaud Mejean, Christophe Legendre, Rebecca Sberro-Soussan
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is an orphan disease with a high rate of recurrence after kidney transplantation. However, reports of successful prevention of posttransplant aHUS recurrence with eculizumab emerged a few years ago. To further delineate its optimal use, we describe the largest series of kidney transplant recipients treated with prophylactic eculizumab. METHODS: Twelve renal transplant recipients with aHUS-related end stage renal disease received eculizumab: 10 from day 0 and 2 at the time of recurrence (days 6 and 25)...
August 25, 2017: Transplantation
https://www.readbyqxmd.com/read/28852487/rare-genetic-variants-in-shiga-toxin-associated-haemolytic-uraemic-syndrome-genetic-analysis-prior-to-transplantation-is-essential
#10
Frances Dowen, Katrina Wood, Alison L Brown, Jennifer Palfrey, David Kavanagh, Vicky Brocklebank
We present a case of haemolytic uraemic syndrome (HUS) in a 16-year-old female with serological evidence of acute Escherichia coli O157:H7 infection. She progressed to established renal failure and received a deceased donor kidney transplant. Shiga toxin-associated HUS (STEC-HUS) does not recur following renal transplantation, but unexpectedly this patient did experience rapid and severe HUS recurrence. She responded to treatment with the terminal complement inhibitor eculizumab and subsequent genetic analysis revealed a rare variant in a complement gene...
August 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28838443/first-treatment-of-relapsing-rapidly-progressive-iga-nephropathy-with-eculizumab-after-living-kidney-donation-a-case-report
#11
A L Herzog, C Wanner, K Amann, K Lopau
BACKGROUND: IgA nephropathy (IGAN) rarely can present as a crescent and progressive form leading to end-stage renal disease (ESRD) in a short period of time. Recurrence of IGAN after kidney transplantation is frequent, and complement components such as C3, C4d, and C5 seem to be involved. We present a case of a young male patient with ESRD caused by rapidly progressive IGAN and who demonstrated rapid recurrence of crescentic IGAN after kidney donation. CASE REPORT: In September 2014, a 28-year-old male patient was hospitalized due to IGAN with 60% of crescents...
September 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28836275/impact-of-treatment-and-outcomes-for-patients-with-posttransplant-drug-associated-thrombotic-microangiopathy
#12
Narendranath Epperla, Kathleen Hemauer, Mehdi Hamadani, Kenneth D Friedman, Lisa Baumann Kreuziger
BACKGROUND: Drug-induced transplant-associated thrombotic microangiopathy (DTA-TMA) is a rare but serious complication that can occur after hematopoietic cell transplantation (HCT) or solid organ transplantation (SOT) without guidelines for optimal management of this condition. STUDY DESIGN AND METHODS: Given the ambiguity surrounding the treatment for DTA-TMA, we conducted a retrospective review to evaluate the impact of different treatment strategies in DTA-TMA patients...
August 23, 2017: Transfusion
https://www.readbyqxmd.com/read/28832357/recurrent-glomerular-disease-after-kidney-transplantation
#13
Christopher D Blosser, Roy D Bloom
PURPOSE OF REVIEW: With improving short-term kidney transplant outcomes, recurrent glomerular disease is being increasingly recognized as an important cause of chronic allograft failure. Further understanding of the risks and pathogenesis of recurrent glomerular disease enable informed transplant decisions, along with the development of preventive and treatment strategies. RECENT FINDINGS: Multiple observational studies have highlighted differences in rates and outcomes for various recurrent glomerular diseases, although these rates have not markedly improved over the last decade...
November 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28821363/living-donor-kidney-transplantation-in-atypical-hemolytic-uremic-syndrome-a-case-series
#14
Caroline Duineveld, Jacobien C Verhave, Stefan P Berger, Nicole C A J van de Kar, Jack F M Wetzels
BACKGROUND: The development of complement inhibitors has greatly improved the outcome of patients with atypical hemolytic uremic syndrome (aHUS), making kidney transplantation a more feasible option. Although prophylactic eculizumab therapy may prevent recurrent disease after transplantation, its necessity for all transplant recipients is debated. STUDY DESIGN: A case series. SETTING & PARTICIPANTS: Patients with aHUS who underwent living donor kidney transplantation after 2011 at 2 university centers, prospectively followed up with a protocol of eculizumab therapy limited to only recipients with documented posttransplantation recurrent thrombotic microangiopathy...
August 16, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28801959/outcomes-of-patients-with-atypical-hemolytic-uremic-syndrome-with-native-and-transplanted-kidneys-treated-with-eculizumab-a-pooled-post-hoc-analysis
#15
Christophe M Legendre, Josep M Campistol, Thorsten Feldkamp, Giuseppe Remuzzi, John F Kincaid, Åsa Lommelé, Jimmy Wang, Laurent E Weekers, Neil S Sheerin
Atypical hemolytic uremic syndrome (aHUS) often leads to end-stage renal disease (ESRD) and kidney transplantation; graft loss rates are high due to disease recurrence. A post hoc analysis of four prospective clinical trials in aHUS was performed to evaluate eculizumab, a terminal complement inhibitor, in patients with native or transplanted kidneys. The trials included 26-week treatment and extension periods. Dialysis, transplant, and graft loss were evaluated. Study endpoints included complete thrombotic microangiopathy (TMA) response, TMA event-free status, hematologic and renal parameters, and adverse events...
August 12, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28750931/factor-h-autoantibody-is-associated-with-atypical-hemolytic-uremic-syndrome-in-children-in-the-united-kingdom-and-ireland
#16
Vicky Brocklebank, Sally Johnson, Thomas P Sheerin, Stephen D Marks, Rodney D Gilbert, Kay Tyerman, Meredith Kinoshita, Atif Awan, Amrit Kaur, Nicholas Webb, Shivaram Hegde, Eric Finlay, Maggie Fitzpatrick, Patrick R Walsh, Edwin K S Wong, Caroline Booth, Larissa Kerecuk, Alan D Salama, Mike Almond, Carol Inward, Timothy H Goodship, Neil S Sheerin, Kevin J Marchbank, David Kavanagh
Factor H autoantibodies can impair complement regulation, resulting in atypical hemolytic uremic syndrome, predominantly in childhood. There are no trials investigating treatment, and clinical practice is only informed by retrospective cohort analysis. Here we examined 175 children presenting with atypical hemolytic uremic syndrome in the United Kingdom and Ireland for factor H autoantibodies that included 17 children with titers above the international standard. Of the 17, seven had a concomitant rare genetic variant in a gene encoding a complement pathway component or regulator...
July 24, 2017: Kidney International
https://www.readbyqxmd.com/read/28725563/atypical-hemolytic-uremic-syndrome-triggered-by-varicella-infection
#17
Pauline Condom, Jean-Michel Mansuy, Stéphane Decramer, Jacques Izopet, Catherine Mengelle
Varicella Zoster Virus (VZV) is a well-known virus that belongs to the Herpesviridae family which induces a self-limited disease except in specific cases in particular among stem cell transplant patients. This virus is not known however to trigger atypical Hemolytic Uremic Syndrome (aHUS). Here we report the case of a six-year-old boy who was hospitalized with fever and abdominal pains associated to pruritic and vesicular rash, thrombocytopenia and acute renal failure. He was diagnosed with aHUS precipitated by varicella virus...
2017: IDCases
https://www.readbyqxmd.com/read/28647502/alternative-complement-pathway-hemolytic-assays-reveal-incomplete-complement-blockade-in-patients-treated-with-eculizumab
#18
Bénédicte Puissant-Lubrano, Sylvain Puissochet, Nicolas Congy-Jolivet, Dominique Chauveau, Stéphane Decramer, Arnaud Garnier, Antoine Huart, Nassim Kamar, David Ribes, Antoine Blancher
Eculizumab is a monoclonal anti-C5 antibody used in the treatment of atypical hemolytic uremic syndrome (aHUS). We monitored complement inhibition in 16 eculizumab-treated patients suffering from HUS or transplant rejection (not aHUS patients). Blood samples were obtained one to four weeks after the last eculizumab injection. We observed that eculizumab efficiently blocked the terminal pathway (TP) through classical pathway (CP) activation measured by kinetic hemolytic assay (HA) (<10%) but incompletely blocked the TP through alternative pathway (AP) activation measured by rabbit (APH50>23%) or chicken erythrocytes HA (AP100>15%)...
June 21, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28596415/hemolytic-uremic-syndrome-in-pregnancy-and-postpartum
#19
Alexandra Bruel, David Kavanagh, Marina Noris, Yahsou Delmas, Edwin K S Wong, Elena Bresin, François Provôt, Vicky Brocklebank, Caterina Mele, Giuseppe Remuzzi, Chantal Loirat, Véronique Frémeaux-Bacchi, Fadi Fakhouri
BACKGROUND: Pregnancy is associated with various forms of thrombotic microangiopathy, including hemolytic uremic syndrome. A previous small French study suggested that pregnancy-associated hemolytic uremic syndrome was to be included in the spectrum of atypical hemolytic uremic syndrome linked to complement alternative pathway dysregulation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We sought to retrospectively analyze the presentation, outcome, and frequency of complement alternative pathway gene variants in a larger international (France, United Kingdom, Italy) cohort of patients with pregnancy-associated hemolytic uremic syndrome...
August 7, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28538511/successful-treatment-of-transplantation-associated-atypical-hemolytic-uremic-syndrome-with-eculizumab
#20
Daiichiro Hasegawa, Atsuro Saito, Nanako Nino, Suguru Uemura, Satoru Takafuji, Takehito Yokoi, Aiko Kozaki, Toshiaki Ishida, Keiichiro Kawasaki, Takahiro Yasumi, Naoki Sakata, Yasufumi Ohtsuka, Satoshi Hirase, Takeshi Mori, Noriyuki Nishimura, Mayumi Kusumoto, Yoshiharu Ogawa, Kenta Tominaga, Taku Nakagawa, Kyoko Kanda, Ryojiro Tanaka, Yoshiyuki Kosaka
We herein reported a 4-month-old boy with transplantation-associated atypical hemolytic uremic syndrome (TA-aHUS) who was successfully treated with eculizumab. The patient diagnosed with type 3 of familial hemophagocytic lymphohistiocytosis underwent cord blood transplantation. After transplantation, he developed TA-aHUS, but plasma exchanges were unsuccessful. We identified deletions in CFH-related gene 1 (del-CFHR1) by the multiplex ligation-dependent probe amplification testing procedure and CFH autoantibodies...
June 22, 2017: Journal of Pediatric Hematology/oncology
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