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https://www.readbyqxmd.com/read/28058212/complement-related-kidney-diseases-recurrence-after-transplantation
#1
REVIEW
Maurizio Salvadori, Elisabetta Bertoni
The recurrence of renal disease after renal transplantation is becoming one of the main causes of graft loss after kidney transplantation. This principally concerns some of the original diseases as the atypical hemolytic uremic syndrome (HUS), the membranoproliferative glomerulonephritis (MPGN), in particular the MPGN now called C3 glomerulopathy. Both this groups of renal diseases are characterized by congenital (genetic) or acquired (auto-antibodies) modifications of the alternative pathway of complement...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28056875/turkish-pediatric-atypical-hemolytic-uremic-syndrome-registry-initial-analysis-of-146-patients
#2
Nesrin Besbas, Bora Gulhan, Oguz Soylemezoglu, Z Birsin Ozcakar, Emine Korkmaz, Mutlu Hayran, Fatih Ozaltin
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a devastating disease with significant morbidity and mortality. Its genetic heterogeneity impacts its clinical presentation, progress, and outcome, and there is no consensus on its clinical management. METHODS: To identify the characteristics of aHUS in Turkish children, an industry-independent registry was established for data collection that includes both retrospective and prospective patients. RESULTS: In total, 146 patients (62 boys, 84 girls) were enrolled; 53 patients (36...
January 5, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28056758/thrombotic-management-of-antiphospholipid-syndrome-towards-novel-targeted-therapies
#3
Md Asiful Islam, Fahmida Alam, Kah Keng Wong, Mohammad Amjad Kamal, Siew Hua Gan
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis and/or pregnancy morbidity with persistent levels of antiphospholipid antibodies (aPLs). The development of thrombosis in APS is mediated by aPLs and contributes to the high mortality rate in APS patients. However, although APS has been reported for more than 30 years, there has been no optimal regimen for its prevention or for the management of thrombosis, mainly because the mainstay treatment strategies for managing APS are not targeted towards aPL-mediated thrombotic pathophysiology...
5, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28045484/development-of-autologous-c5-vaccine-nanoparticles-to-reduce-intravascular-hemolysis-in-vivo
#4
Lingjun Zhang, Wen Qiu, Stephen Crooke, Yan Li, Areeba Abid, Bin Xu, M G Finn, Feng Lin
The complement system is emerging as a new target for treating many diseases. For example, Eculizumab, a humanized monoclonal antibody against complement component 5 (C5), has been approved for paroxysmal nocturnal hemoglobinuria (PNH) in which patient erythrocytes are lysed by complement. In this study, we developed vaccines to elicit autologous anti-C5 antibody production in mice for complement inhibition. Immunization of mice with a conservative C5 xenoprotein raised high titers of IgG's against the xenogenous C5, but these antibodies did not reduce C5 activity in the blood...
January 12, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28028023/incomplete-inhibition-by-eculizumab-mechanistic-evidence-for-residual-c5-activity-during-strong-complement-activation
#5
Markus J Harder, Nadine Kuhn, Hubert Schrezenmeier, Britta Höchsmann, Inge von Zabern, Christof Weinstock, Thomas Simmet, Daniel Ricklin, John D Lambris, Arne Skerra, Markus Anliker, Christoph Q Schmidt
Eculizumab inhibits the terminal, lytic pathway of complement by blocking the activation of the complement protein C5 and shows remarkable clinical benefits in certain complement-mediated diseases. However, several reports suggest that activation of C5 is not always completely suppressed in patients even under excess of eculizumab over C5 indicating that residual C5 activity may derogate the drug's therapeutic benefit under certain conditions. By using eculizumab and the tick-derived C5 inhibitor coversin we determine conditions ex vivo in which C5-inhibition is incomplete...
December 27, 2016: Blood
https://www.readbyqxmd.com/read/28025630/adjustment-of-eculizumab-dosage-pattern-in-patients-with-atypical-hemolytic-uremic-syndrome-with-suboptimal-response-to-standard-treatment-pattern
#6
Camino García Monteavaro, Carmen Peralta Roselló, Borja Quiroga, José María Baltar Martín, Lorena Castillo Eraso, Fernando de Álvaro Moreno, Alberto Martínez Vea, María Teresa Visus-Fernández de Manzanos
In patients with atypical hemolytic uremic syndrome (aHUS), complement blocking by eculizumab rapidly halts the process of thrombotic microangiopathy and it is associated with clear long-term hematologic and renal improvements. Eculizumab treatment consists of a 4-week initial phase with weekly IV administration of 900 mg doses, followed by a maintenance phase with a 1,200 mg dose in the fifth week and every 14 ± 2 days thereafter. We present three patients with aHUS and suboptimal response to eculizumab treatment at the usual administration dosage who showed hematologic and renal improvements after an adjustment in the eculizumab treatment protocol...
2016: Case Reports in Nephrology
https://www.readbyqxmd.com/read/28010051/qmg-and-mg-adl-correlations-study-of-eculizumab-treatment-of-myasthenia-gravis
#7
James F Howard, Miriam Freimer, Fanny O'Brien, Jing Jing Wang, Stephen R Collins, John T Kissel, Laura Herbelin, April L McVey, Mazen M Dimachkie, Mamatha Pasnoor, Debbie Lu, Alexander Waltz, Vinay Chaudhry, Andrea Corse, Elizabeth Mosmiller, Caroline Klein, Manisha Chopra, Elizabeth Richardson, Janice M Massey, Lisa D Hobson-Webb, Jeffrey Guptill, Wendy King, Annabel K Wang, Kaveh Saremi, Patricia A Tully, Denise Davis, Veronica Martin, Robert M Pascuzzi, Sandy Guingrich, Angela Micheels, Michael Pulley, Kenneth Hentschel, Lisa Smith, Rhonda Calhoun, James Gilchrist, George Sachs, Brigid Crabtree, Elena Kim Perez, Kenneth Gorson, Elizabeth Harrahy Cobb, Elinita Rosseto, Zaeem Siddiqi, Syed Nizamuddin Ahmed, Derrick Blackmore, Shannon Butler-Tyler, Sarah Louise Miller, Caroline Carmichael, Ted Burns, William David, Peter Donofrio, Bashar Katirji, Richard Lewis, Shin Oh, David Richman, Mark Sivak, Rup Tandan, Gil Wolfe, Shawn Bird, David Hilton-Jones
INTRODUCTION: A phase 2 study of eculizumab for treating myasthenia gravis (MG) used the quantitative myasthenia gravis score (QMG) and myasthenia gravis activities of daily living profile (MG-ADL) to evaluate baseline disease severity and treatment response. Correlations were then analyzed between these assessments. METHODS: Patients were given eculizumab or placebo during the first 16-week treatment period of the crossover study, with treatment assignments reversed for the second treatment period following a 5-week washout...
December 23, 2016: Muscle & Nerve
https://www.readbyqxmd.com/read/28004336/quantification-of-the-igg2-4-kappa-monoclonal-therapeutic-eculizumab-from-serum-using-isotype-specific-affinity-purification-and-microflow-lc-esi-q-tof-mass-spectrometry
#8
Paula M Ladwig, David R Barnidge, Maria A V Willrich
As therapeutic monoclonal antibodies (mAbs) become more humanized, traditional tryptic peptide approaches used to measure biologics in serum become more challenging since unique clonotypic peptides used for quantifying the mAb may also be found in the normal serum polyclonal background. An alternative approach is to monitor the unique molecular mass of the intact light chain portion of the mAbs using liquid chromatography-mass spectrometry (LC-MS). Distinguishing a therapeutic mAb from a patient's normal polyclonal immunoglobulin (Ig) repertoire is the primary limiting factor when determining the limit of quantitation (LOQ) in serum...
December 21, 2016: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/27990486/successful-simultaneous-liver-kidney-transplantation-in-the-presence-of-multiple-high-titered-class-i-and-ii-antidonor-hla-antibodies
#9
Flavio Paterno, Alin Girnita, Paul Brailey, David Witte, Jiang Wang, Madison C Cuffy, Tayyab Diwan, Simon Tremblay, Jane Y Revollo, Rita R Alloway, Michael R Schoech, Nadim Anwar, Shimul A Shah, Steve E Woodle
The results of simultaneous liver-kidney transplants in highly sensitized recipients have been controversial in terms of antibody-mediated rejection and kidney allograft outcomes. This case report provides a detailed and sophisticated documentation of histocompatibility and pathologic data in a simultaneous liver-kidney transplant performed in a recipient with multiple high-titered class I and II antidonor HLA antibodies and a strongly positive cytotoxic crossmatch. Patient received induction with steroids, rituximab, and eculizumab without lymphocyte depleting agents...
December 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27987277/eculizumab-refractory-thrombotic-thrombocytopenic-purpura-secondary-to-post-endoscopic-retrograde-cholangiopancreatography-pancreatitis-in-a-patient
#10
Faizan Malik, Naveed Ali, Irfan Ahsan, Ali Raza Ghani, Christian Fidler
Thrombotic thrombocytopenic purpura (TTP) is a rare multisystem microvascular disorder, which is characterized by pentad of thrombocytopenia, microangiopathic hemolytic anemia, and organ dysfunction due to occlusive thrombi. The proposed pathophysiology involves an imbalance between unusually large von Willebrand factor multimers and the cleaving protease ADAMTS13. Acute pancreatitis is a well-described consequence of TTP, but TTP secondary to acute pancreatitis is a rare phenomenon. We present a patient who developed TTP due to post-ERCP pancreatitis with hematologic, cardiovascular, pulmonary, and renal complications and is the first case of this kind...
2016: Journal of Community Hospital Internal Medicine Perspectives
https://www.readbyqxmd.com/read/27974740/a-case-report-and-literature-review-of-eculizumab-withdrawal-in-atypical-hemolytic-uremic-syndrome
#11
Borja Quiroga, Alberto de Lorenzo, Cristina Vega, Fernando de Alvaro
BACKGROUND Recent advances in the treatment of atypical hemolytic-uremic syndrome (aHUS) have resulted to better long-term survival rates for patients with this life-threatening disease. However, many questions remain such as whether or not long-term treatment is necessary in some patients and what are the risks of prolonged therapy. CASE REPORT Here, we discuss the case of a 37-year-old woman with CFH and CD46 genetic abnormalities who developed aHUS with severe renal failure. She was successfully treated with three doses of rituximab and a three month treatment with eculizumab...
December 15, 2016: American Journal of Case Reports
https://www.readbyqxmd.com/read/27974406/thrombotic-microangiopathy-in-inverted-formin-2-mediated-renal-disease
#12
Rachel C Challis, Troels Ring, Yaobo Xu, Edwin K S Wong, Oliver Flossmann, Ian S D Roberts, Saeed Ahmed, Michael Wetherall, Giedrius Salkus, Vicky Brocklebank, Julian Fester, Lisa Strain, Valerie Wilson, Katrina M Wood, Kevin J Marchbank, Mauro Santibanez-Koref, Timothy H J Goodship, David Kavanagh
The demonstration of impaired C regulation in the thrombotic microangiopathy (TMA) atypical hemolytic uremic syndrome (aHUS) resulted in the successful introduction of the C inhibitor eculizumab into clinical practice. C abnormalities account for approximately 50% of aHUS cases; however, mutations in the non-C gene diacylglycerol kinase-ε have been described recently in individuals not responsive to eculizumab. We report here a family in which the proposita presented with aHUS but did not respond to eculizumab...
December 14, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27964705/biological-drugs-in-guillain-barr%C3%A3-syndrome-an-update
#13
Nazgol Motamed-Gorji, Nassim Matin, Omidreza Tabatabaie, Piero Pavone, Catia Romano, Raffaele Falsaperla, Giovanna Vitaliti
BACKGROUND: Guillain-Barré Syndrome (GBS) is currently considered the most common global cause of acute flaccid paralysis. Currently, standard therapy for Guillain-Barré Syndrome includes intravenous immunoglobulin or plasma exchange. Despite medical advances regarding these treatments many patients treated with them do not reach full recovery. Therefore, during last decades several biological agents have attracted the attentions from researchers and various studies have investigated their role in Guillain-Barré Syndrome...
December 13, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/27932157/belatacept-and-eculizumab-for-treatment-of-calcineurin-inhibitor-induced-thrombotic-microangiopathy-after-kidney-transplantation-case-report
#14
J Merola, P S Yoo, J Schaub, J D Smith, M I Rodriguez-Davalos, E Tichy, D C Mulligan, W Asch, R Formica, M Kashgarian, S Kulkarni
Thrombotic microangiopathy (TMA) after kidney transplantation is an uncommon and challenging cause of graft dysfunction and is associated with early graft loss. An idiosyncratic endothelial reaction to calcineurin inhibitors (CNIs) has been implicated as a frequent cause of TMA. This reaction is marked by uncontrolled activation of complement and subsequent cellular destruction. Usual therapy consists of withdrawal of the inciting drug and plasmapheresis to minimize levels of circulating complement. Recently, eculizumab, a monoclonal antibody to complement component C5, has been used for the treatment of atypical hemolytic uremic syndrome...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27932156/dosing-eculizumab-for-antibody-mediated-rejection-in-kidney-transplantation-a-case-report
#15
B Smith, V Kumar, D Mompoint-Williams, R D Reed, P A MacLennan, K Stegner, J E Locke
Severe antibody-mediated rejection (AMR) of a blood type-incompatible (ABOi) living donor kidney transplantation (LDKT) can lead to graft failure, and aggressive therapies, such as the anticomplement antibody eculizumab, are often used to rescue the affected graft. Eculizumab therapy can be crippling financially. Current literature suggests a wide variation in the amount and timing of eculizumab given as rescue therapy in the setting of AMR. Herein we describe a limited-eculizumab regimen in the setting of severe AMR that is both clinically and cost effective...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27904864/nephrotic-range-proteinuria-and-peripheral-edema-in-a-child-not-only-idiopathic-nephrotic-syndrome
#16
Valentina Dolcemascolo, Marina Vivarelli, Manuela Colucci, Francesca Diomedi-Camassei, Rossella Piras, Marta Alberti, Francesco Emma
Hemolytic uremic syndrome (HUS) is defined by the simultaneous occurrence of hemolytic anemia, thrombocytopenia, and acute kidney injury due to thrombotic microangiopathy (TMA) mainly occurring in renal and cerebral microvessels. Although the most common cause of HUS in children is Shiga toxin-producing Escherichia coli, atypical forms in which Shiga toxin is not the trigger may occur. Research over the last few years has shown that complement dysregulation secondary to mutations of genes coding for proteins involved in the regulation of the alternative pathway of complement account for most forms of atypical HUS (aHUS)...
September 2016: Case Reports in Nephrology and Dialysis
https://www.readbyqxmd.com/read/27886797/catastrophic-antiphospholipid-syndrome-the-current-management-approach
#17
REVIEW
Ignasi Rodriguez-Pintó, Gerard Espinosa, Ricard Cervera
The current recommendation for catastrophic antiphospholipid syndrome (CAPS) management is the standard triple therapy with anticoagulation (AC), glucocorticoids (GCs), plasma exchange (PE), and/or intravenous immunoglobulins (IVIGs). Of note, only AC has a significant effect on the prognosis of these patients. However, from the experimental or basic point of view, there is only indirect evidence to advocate the use of these immunomodulatory therapies (GC, PE, and IVIG) in CAPS. Recently, there have been reports of severe or refractory CAPS patients treated with the monoclonal antibodies rituximab and eculizumab...
April 2016: Best Practice & Research. Clinical Rheumatology
https://www.readbyqxmd.com/read/27879189/gemcitabine-induced-hemolytic-uremic-syndrome-treated-with-eculizumab-or-plasmapheresis-two-case-reports%C3%A2
#18
María Esperanza López Rubio, Raquel Rodado Martínez, María Luisa Illescas, Encarnación Mateo Bosch, Mercedes Martinez Díaz, Lourdes de la Vara Inesta, Basilio Cabezuelo, María Elisa Morales Albuja, Eladio Lucas Guillén, Luisa Jimeno García
BACKGROUND: Drug-induced hemolytic-uremic syndrome (HUS) has shown good response to eculizumab (ECU). We present 2 cases of patients with gemcitabine-induced HUS (GEM-HUS), one of whom was treated with ECU and the other with conventional treatment. Patient 1: A 74-year-old male with resected adenocarcinoma of the pancreas started adjuvant treatment with GEM, but after 5 months GEM was discontinued due to acute kidney injury and severe hypertension. Laboratory analyses identified microangiopathic hemolytic anemia (MHA) and thrombocytopenia...
February 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/27871301/an-innovative-and-collaborative-partnership-between-patients-with-rare-disease-and-industry-supported-registries-the-global-ahus-registry
#19
REVIEW
Len Woodward, Sally Johnson, Johan Vande Walle, Joran Beck, Christoph Gasteyger, Christoph Licht, Gema Ariceta
BACKGROUND: Patients are becoming increasingly involved in research which can promote innovation through novel ideas, support patient-centred actions, and facilitate drug development. For rare diseases, registries that collect data from patients can increase knowledge of the disease's natural history, evaluate clinical therapies, monitor drug safety, and measure quality of care. The active participation of patients is expected to optimise rare-disease management and improve patient outcomes...
November 21, 2016: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/27857121/guillain-barr%C3%A3-syndrome-a-century-of-progress
#20
REVIEW
John A Goodfellow, Hugh J Willison
In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts - novel findings that identified the disease we now know as Guillain-Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise...
November 18, 2016: Nature Reviews. Neurology
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