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https://www.readbyqxmd.com/read/29226095/atypical-hemolytic-uremic-syndrome-due-to-complement-factor-i-mutation
#1
Abdullah H Almalki, Laila F Sadagah, Mohammed Qureshi, Hatim Maghrabi, Abdulrahman Algain, Ahmed Alsaeed
Atypical hemolytic-uremic syndrome (aHUS) is a rare disease of complement dysregulation leading to thrombotic microangiopathy (TMA). Renal involvement and progression to end-stage renal disease are common in untreated patients. We report a 52-year-old female patient who presented with severe acute kidney injury, microangiopathic hemolytic anemia, and thrombocytopenia. She was managed with steroid, plasma exchange, and dialysis. Kidney biopsy shows TMA and renal cortical necrosis. Genetic analysis reveals heterozygous complement factor I (CFI) mutation...
November 6, 2017: World Journal of Nephrology
https://www.readbyqxmd.com/read/29225827/gemcitabine-and-carfilzomib-induced-thrombotic-microangiopathy-eculizumab-as-a-life-saving-treatment
#2
Rahul Gosain, Amitoj Gill, Jacob Fuqua, Lesley H Volz, Mika R Kessans Knable, Ryan Bycroft, Sarah Seger, Rohit Gosain, Jorge A Rios, Ju-Hsien Chao
Drug-induced aHUS is rare; however, early diagnosis is vital to reduce morbidity and mortality. With confirmation of the diagnosis, eculizumab appears to be a viable treatment option to suppress the pro-inflammatory surge. Furthermore, adverse side effects of medications such as carfilzomib and gemcitabine should be considered in the appropriate settings.
December 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/29225802/effective-immunosuppressive-management-with-belatacept-and-eculizumab-in-post-transplant-ahus-due-to-a-homozygous-deletion-of-cfhr1-cfhr3-and-the-presence-of-cfh-antibodies
#3
Johannes Münch, Anette Bachmann, Maik Grohmann, Christof Mayer, Michael Kirschfink, Tom H Lindner, Carsten Bergmann, Jan Halbritter
Atypical haemolytic uraemic syndrome (aHUS) may clinically present as acute renal graft failure resulting from excessive activation of the complement cascade. While mutations of complement-encoding genes predispose for aHUS, it is generally thought to require an additional insult (e.g. drugs) to trigger and manifest the full-blown clinical syndrome. Calcineurin inhibitors (CNIs) used for immunosuppression act as potential triggers, especially in the post-transplantation setting. Therefore, CNI-free immunosuppressive regimens may be beneficial...
December 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/29214126/pharmacologic-complement-inhibition-in-clinical-transplantation
#4
REVIEW
Vasishta S Tatapudi, Robert A Montgomery
Purpose of Review: Over the past two decades, significant strides made in our understanding of the etiology of antibody-mediated rejection (AMR) in transplantation have put the complement system in the spotlight. Here, we review recent progress made in the field of pharmacologic complement inhibition in clinical transplantation and aim to understand the impact of this therapeutic approach on outcomes in transplant recipients. Recent Findings: Encouraged by the success of agents targeting the complement cascade in disorders of unrestrained complement activation like paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), investigators are testing the safety and efficacy of pharmacologic complement blockade in mitigating allograft injury in conditions ranging from AMR to recurrent post-transplant aHUS, C3 glomerulopathies and antiphospholipid anti-body syndrome (APS)...
2017: Current Transplantation Reports
https://www.readbyqxmd.com/read/29212979/-clinical-features-and-quality-of-life-assessment-in-japanese-pnh-patients-enrolled-in-the-international-pnh-registry
#5
Masatoshi Sakurai, Shinichiro Okamoto
The aim of the present study was to clarify the clinical characteristics and quality of life (QOL) of Japanese patients (N=116) enrolled in the International PNH Registry, compared to the whole registry cohort (N=3,457), censored as of March 2015. The proportion of patients treated with eculizumab was comparable between the two cohorts; the Japanese cohort showed higher levels of lactate dehydrogenase and lower hemoglobin values at baseline. Compared to the whole cohort, the Japanese cohort had a greater incidence of bone marrow failure (67...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29199277/the-renaissance-of-complement-therapeutics
#6
REVIEW
Daniel Ricklin, Dimitrios C Mastellos, Edimara S Reis, John D Lambris
The increasing number of clinical conditions that involve a pathological contribution from the complement system - many of which affect the kidneys - has spurred a regained interest in therapeutic options to modulate this host defence pathway. Molecular insight, technological advances, and the first decade of clinical experience with the complement-specific drug eculizumab, have contributed to a growing confidence in therapeutic complement inhibition. More than 20 candidate drugs that target various stages of the complement cascade are currently being evaluated in clinical trials, and additional agents are in preclinical development...
December 4, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/29157988/de-novo-thrombotic-microangiopathy-after-kidney-transplantation
#7
REVIEW
Neetika Garg, Helmut G Rennke, Martha Pavlakis, Kambiz Zandi-Nejad
Thrombotic microangiopathy (TMA) is a serious complication of transplantation that adversely affects kidney transplant recipient and allograft survival. Post-transplant TMA is usually classified into two categories: 1) recurrent TMA and 2) de novo TMA. Atypical hemolytic uremic syndrome (aHUS) resulting from dysregulation and over-activation of the alternate complement pathway is a rare disease but the most common diagnosis associated with recurrence in the allografts. De novo TMA, on the other hand, represents an overwhelming majority of the cases of post-transplant TMA and is a substantially more heterogeneous entity than recurrent aHUS...
November 4, 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/29156357/generation-of-complement-molecular-complex-c5b-9-c5b-9-in-response-to-poly-traumatic-hemorrhagic-shock-and-evaluation-of-c5-cleavage-inhibitors-in-non-human-primates
#8
R Madelaine Paredes, Sarah Reyna, Philip Vernon, Douglas K Tadaki, Jurandir J Dallelucca, Forest Sheppard
Severe trauma initiates a systemic inflammatory cascade and that involves early activation of complement and cleavage of C5 into C5a (anaphylatoxin) and C5b (C5b-9 membrane attack complex). We examined activation of C5 in non-human primate (NHP) models of hemorrhagic shock. Blood plasma concentrations of C5b-9 were significantly increased in NHPs in response to hemorrhage alone and were further increased with the addition of tissue trauma. The onset of increased C5 cleavage was accelerated in NHPs that experienced decompensated poly-traumatic hemorrhagic shock...
November 17, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29152520/a-case-of-escherichia-coli-hemolytic-uremic-syndrome-in-a-10-year-old-male-with-severe-neurologic-involvement-successfully-treated-with-eculizumab
#9
Malia Rasa, James Musgrave, Keith Abe, Len Tanaka, Konstantine Xoinis, Bruce Shiramizu, Gretchen Foskett, Rhiana Lau
Hemolytic uremic syndrome (HUS) can be classified as typical and atypical, and the treatment recommendations currently differ between the 2 types. Eculizumab is recommended as first-line treatment for atypical HUS; however, its use in typical HUS has been controversial. We report a case of a 10-year-old male with severe neurologic impairment who was successfully treated with eculizumab, which was started 4 days after onset of neurologic symptoms. Our case supports the use of eculizumab in typical HUS with neurologic involvement, even when given later in the course, as the pathophysiology of typical HUS has been shown to involve activation of the complement pathway, similar to atypical HUS...
October 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/29147590/paroxysmal-nocturnal-hemoglobinuria-in-pregnancy-a-dilemma-in-treatment-and-thromboprophylaxis
#10
Arpan Patel, Athira Unnikrishnan, Martina Murphy, Robert Egerman, Sarah Wheeler, Ashley Richards, John Wingard
Paroxysmal nocturnal hemoglobinuria (PNH) is a hematologic disorder characterized by an acquired somatic mutation in the phosphatidylinositol glycan class A gene which leads to a higher risk for increased venous and arterial thrombosis. Current treatment for PNH includes eculizumab. Pregnant patients who have PNH have higher risk for thrombosis and hemorrhage with both pregnancy and their underlying PNH. Treatment frequently poses conundrum. The safety and efficacy of eculizumab during pregnancy and breast feeding have not been extensively studied and contraception has been recommended due to potential for teratogenicity...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/29138283/frequency-of-and-reasons-for-paroxysmal-nocturnal-haemoglobinuria-screening-in-patients-with-unexplained-anaemia
#11
James T England, Bakul Dalal, Heather A Leitch
Referral to hematology for anemia is common. In paroxysmal nocturnal hemoglobinuria (PNH), cells deficient in the glycosylphosphatidyl inositol (GPI) anchor are lysed by complement. Eculizumab improves overall survival and quality of life while reducing hemolysis, transfusion requirements, and thrombosis. We evaluated the frequency of screening for PNH in patients with unexplained anemia. Key clinical features, laboratory data, and investigations were recorded for patients referred for anemia since 2010, without a specific cause found...
November 14, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29136640/long-term-outcomes-of-the-atypical-hemolytic-uremic-syndrome-after-kidney-transplantation-treated-with-eculizumab-as-first-choice
#12
Luis Gustavo Modelli de Andrade, Mariana Moraes Contti, Hong Si Nga, Ariane Moyses Bravin, Henrique Mochida Takase, Rosa Marlene Viero, Trycia Nunes da Silva, Kelem De Nardi Chagas, Lilian Monteiro Pereira Palma
INTRODUCTION: The treatment of choice for Atypical Hemolytic Uremic Syndrome (aHUS) is the monoclonal antibody eculizumab. The objective of this study was to assess the efficacy and safety of eculizumab in a cohort of kidney transplant patients suffering from aHUS. METHODS: Description of the prospective cohort of all the patients primarily treated with eculizumab after transplantation and divided into the therapeutic (onset of aHUS after transplantation) and prophylactic use (patients with previous diagnosis of aHUS undergoing kidney transplantation)...
2017: PloS One
https://www.readbyqxmd.com/read/29136616/no-relapse-of-calcineurin-inhibitor-associated-thrombotic-microangiopathy-after-discontinuation-of-eculizumab
#13
Thomas Neumann, Andrzej Plis, Martin Weigel, Sylvia Stracke, Sigrun Friesecke, Stephanie-Susanne Stecher, Laila Schneidewind, Christoph Busemann, Christian Andreas Schmidt, William H Krüger
No abstract text is available yet for this article.
November 15, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/29131151/combined-intensive-immunosuppression-and-eculizumab-for-aplastic-anemia-in-the-context-of-hemolytic-paroxysmal-nocturnal-hemoglobinuria-a-retrospective-analysis
#14
S Pagliuca, A M Risitano, F S De Fontbrune, M Robin, A P Iori, S Marotta, D Michonneau, A Villate, D Desmier, G Socié, R P De Latour
No abstract text is available yet for this article.
November 13, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29106598/safety-and-effectiveness-of-restrictive-eculizumab-treatment-in-atypical-haemolytic-uremic-syndrome
#15
Kioa L Wijnsma, Caroline Duineveld, Elena B Volokhina, Lambertus P van den Heuvel, Nicole C A J van de Kar, Jack F M Wetzels
Background: Atypical haemolytic uremic syndrome (aHUS) is a rare but severe form of thrombotic microangiopathy as a consequence of complement dysregulation. aHUS has a poor outcome with high mortality and >50% of patients developing end-stage renal disease. Since the end of 2012, these outcomes have greatly improved with the introduction of eculizumab. Currently the duration of treatment is debated. Most guidelines advise lifelong treatment. However, there is no hard evidence to support this advice...
July 4, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29102415/hereditary-hemochromatosis-manifesting-after-treatment-of-paroxysmal-nocturnal-hemoglobinuria-with-eculizumab
#16
Elizabeth Elliott, Salman Waheed, Sahr Syed, Sheila Eswaran, Stephanie Gregory, Jamile Shammo
No abstract text is available yet for this article.
October 7, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29097196/recurrent-allograft-c3-glomerulonephritis-and-unsuccessful-eculizumab-treatment
#17
Kati Kaartinen, Leena Martola, Anne Räisänen-Sokolowski, Seppo Meri
There is a great lack of efficient treatments for membranoproliferative glomerulonephritis (MPGN) and recently emerged complement therapies have been proposed to be useful. We report a patient with a complement-mediated MPGN having recurrencies in kidney allografts and an unsuccessful treatment with complement inhibitor, eculizumab (anti-C5 monoclonal antibody). Nephritic factor (C3Nef), an autoantibody against C3bBb, in the patient serum activated C3 but not C5 showing that major damage was mediated by C3 activation with clearly less involvement of C5 explaining unresponsiveness to eculizumab...
October 31, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29094316/neisseria-cinerea-bacteremia-in-a-patient-receiving-eculizumab-a-case-report
#18
Thomas L Walsh, Holly R Bean, Robert B Kaplan
Neisseria cinerea is a commensal species capable of colonizing the upper respiratory tract of humans. Bacteremia associated with this organism is very uncommon, with only seven previous cases described. We report a case of Neisseria cinerea bacteremia in a patient maintained on indefinite eculizumab therapy. It is the eighth reported case of Neisseria cinerea bacteremia and represents the first case in a patient receiving eculizumab.
November 1, 2017: Infection
https://www.readbyqxmd.com/read/29069327/the-role-of-complement-inhibition-in-kidney-transplantation
#19
C Legendre, R Sberro-Soussan, J Zuber, V Frémeaux-Bacchi
Introduction and background: The complement system which belongs to the innate immune system acts both as a first line of defence against various pathogens and as a guardian of host homeostasis. The role of complement has been recently highlighted in several aspects of kidney transplantation: ischaemia-reperfusion, antibody-mediated rejection and native kidney disease recurrence. Sources of data: Experimental data, availability of complement-blocking molecules (mainly the anti-C5 monoclonal antibody, eculizumab) and several trials in human kidney transplant recipients has led to some areas of agreement and some disappointment...
October 21, 2017: British Medical Bulletin
https://www.readbyqxmd.com/read/29066164/eculizumab-a-treatment-option-for-mysthenia-gravis
#20
Nils Erik Gilhus
No abstract text is available yet for this article.
October 20, 2017: Lancet Neurology
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