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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
#1
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/28799704/the-nature-consequences-and-management-of-neurological-disorders-in-chronic-kidney-disease
#2
REVIEW
Bahman Jabbari, Nosratola D Vaziri
Perhaps no other organ in the body is affected as often and in as many ways as the brain is in patients with chronic kidney disease (CKD). Several factors contribute to the neurological disorders in CKD including accumulation of uremic toxins, metabolic and hemodynamic disorders, oxidative stress, inflammation, and impaired blood brain barrier among others. The neurological disorders in CKD involve both peripheral and central nervous system. The peripheral neurological symptoms of CKD are due to somatic and cranial peripheral neuropathies as well as a myopathy...
August 11, 2017: Hemodialysis International
https://www.readbyqxmd.com/read/28798244/atypical-haemolytic-uremic-syndrome-ahus-and-membranoproliferative-glomerulonephritis-mpgn-different-diseases-or-a-spectrum-of-complement-mediated-glomerular-diseases
#3
Ghada A Ankawi, William F Clark
Historically, patients with kidney diseases caused by genetic or acquired dysregulation of the complement alternative pathway have been grouped into clinical syndromes, C3 glomerulopathy (C3GN/DDD) and thrombotic microangiopathy (TMA), specifically atypical haemolytic uremic syndrome (aHUS). Recent data suggested that these diseases share a common pathophysiology and that patients can transition between glomerulopathies in this spectrum. Histopathologically, the main difference cited is the immunofluorescence (IF) findings, with C3 predominance in C3 glomerulopathy (compared with immunoglobulins and complements in immune complex-mediated membranoproliferative glomerulonephritis (MPGN)) and negative IF in TMA...
August 10, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28794069/phase-i-study-of-the-anti-cd22-immunotoxin-moxetumomab-pasudotox-for-childhood-acute-lymphoblastic-leukemia
#4
Alan S Wayne, Nirali N Shah, Deepa Bhojwani, Lewis B Silverman, James A Whitlock, Maryalice Stetler-Stevenson, Weili Sun, Meina Liang, Jie Yang, Robert J Kreitman, Mark C Lanasa, Ira Pastan
Novel therapies are needed to overcome chemotherapy resistance for children with relapsed/refractory acute lymphoblastic leukemia (ALL). Moxetumomab pasudotox is a recombinant anti-CD22 immunotoxin. A multicenter, phase I study was conducted to determine the maximum tolerated cumulative dose (MTCD) and evaluate safety, activity, pharmacokinetics, and immunogenicity of moxetumomab pasudotox in children, adolescents, and young adults with ALL (n=55). Moxetumomab pasudotox was administered as a 30-minute intravenous infusion at doses of 5 to 50 µg/kg every other day (QOD) for six (Cohorts A and B) or 10 (Cohort C) doses, on 21-day cycles...
August 9, 2017: Blood
https://www.readbyqxmd.com/read/28780656/hus-induced-cardiac-and-circulatory-failure-is-reversible-using-cardiopulmonary-bypass-as-rescue
#5
René F Andersen, Jesper V Bjerre, Johan V Povlsen, Mette Veien, Konstantinos Kamperis, Søren Rittig
BACKGROUND: Extra-renal involvement in hemolytic uremic syndrome (HUS) includes gastrointestinal, pancreatic, hepatic, neurological and cardiac manifestations. The current 3-5% mortality rate in HUS patients is primarily attributed to complications related to the central nervous system and the heart. In this brief report, we illustrate that severe cardiac involvement in a patient with HUS is potentially reversible using cardiopulmonary bypass as rescue. CASE-DIAGNOSIS/TREATMENT: A 12-year-old boy was diagnosed with enterohemorrhagic Escherichia coli-induced HUS related to E...
August 5, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28780041/quinine-induced-thrombotic-microangiopathy-a-report-of%C3%A2-19%C3%A2-patients
#6
Evaren E Page, Dustin J Little, Sara K Vesely, James N George
BACKGROUND: Quinine can cause diverse and severe immune-mediated adverse reactions, including thrombotic microangiopathy (TMA). Our objective was to describe the presenting features and long-term outcomes of patients with quinine-induced TMA. STUDY DESIGN: A case series of 19 patients with quinine-induced TMA treated with plasma exchange. SETTING & PARTICIPANTS: Patients with quinine-induced TMA initially suspected of having thrombotic thrombocytopenic purpura (TTP) were identified among patients enrolled in the Oklahoma TTP-Hemolytic Uremic Syndrome Registry...
August 3, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28766381/development-and-validation-of-an-enzyme-linked-immunosorbent-assay-to-measure-free-eculizumab-concentration-in-serum
#7
Christophe Passot, Céline Desvignes, David Ternant, Theodora Bejan-Angoulvant, Anne-Claire Duveau, Philippe Gatault, Gilles Paintaud
AIM: Eculizumab is a monoclonal antibody toward C5 fraction of the complement system. It is approved to treat paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. To perform pharmacokinetic studies and therapeutic drug monitoring, a validated assay is required. MATERIALS & METHODS: An indirect ELISA with recombinant human C5 sensitized microtiter plates were developed. RESULTS: The assay allows the measurement of free eculizumab concentration in human serum...
August 2, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28765569/locus-of-adhesion-and-autoaggregation-laa-a-pathogenicity-island-present-in-emerging-shiga-toxin-producing-escherichia-coli-strains
#8
David A Montero, Juliana Velasco, Felipe Del Canto, Jose L Puente, Nora L Padola, David A Rasko, Mauricio Farfán, Juan C Salazar, Roberto Vidal
Shiga Toxin-producing Escherichia coli (STEC) are a group of foodborne pathogens associated with diarrhea, dysentery, hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS). Shiga toxins are the major virulence factor of these pathogens, however adhesion and colonization to the human intestine is required for STEC pathogenesis. A subset of STEC strains carry the Locus of Enterocyte Effacement (LEE) pathogenicity island (PAI), which encodes genes that mediate the colonization of the human intestine. While LEE-positive STEC strains have traditionally been associated with human disease, the burden of disease caused by STEC strains that lacks LEE (LEE-negative) has increased recently in several countries; however, in the absence of LEE, the molecular pathogenic mechanisms by STEC strains are unknown...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28764223/frequency-of-polyneuropathy-in-patients-on-long-term-peritoneal-dialysis-treatment
#9
Taner Basturk, Yener Koc, Aarzu Ozdemir Kayalar, Figen Yilmaz, Nuri Baris Hasbal, Tamer Sakaci, Elbis Ahbap, Abdulkadir Unsal
INTRODUCTION: Uremic polyneuropathy is very common among patients with Chronic Kidney Disease (CKD). The patients have electrophysiologic signs of impaired nerve function, although a lower percentage of patients are symptomatic. Electrophysiological parameters are quantitative indices of Polyneuropathy (PNP) severity. AIM: To assess the frequency of PNP in patients on long term Peritoneal Dialysis (PD) treatment. MATERIALS AND METHODS: Twenty three PD patients were analysed, who were receiving dialysis for at least five years and the study population divided into two groups according to duration of PD treatment...
June 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28757042/occurrence-and-characterization-of-stx-and-or-eae-positive-escherichia-coli-isolated-from-wildlife-including-a-typical-epec-strain-from-a-wild-boar
#10
Carla Andrea Alonso, Azucena Mora, Dafne Díaz, Miguel Blanco, David González-Barrio, Francisco Ruiz-Fons, Carmen Simón, Jorge Blanco, Carmen Torres
Shiga toxin-producing E. coli (STEC) and enteropathogenic E. coli (EPEC) strains are food-borne pathogens associated with acute diarrhea. Haemolytic-uremic syndrome (HUS) is often a complication of STEC infection. In order to examine the occurrence, serotypes, virulence and antimicrobial-resistance profiles of STEC and EPEC in wildlife, 326 faecal E. coli strains from 304 clinically healthy animals were analyzed. For this approach stx1, stx2 and eae genes, as well as accessory virulence determinants (ehx, hlyA, saa, tia, bfp, subAB) were PCR-screened and sequenced...
August 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28750931/factor-h-autoantibody-is-associated-with-atypical-hemolytic-uremic-syndrome-in-children-in-the-united-kingdom-and-ireland
#11
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/28747219/role-of-eculizumab-in-a-pediatric-refractory-gemcitabine-induced-thrombotic-microangiopathy-a-case-report
#12
Ludovica Facchini, Maurizio Lucchesi, Alessia Stival, Rosa Maria Roperto, Francesca Melosi, Marco Materassi, Silvia Farina, Veronica Tintori, Maurizio de Martino, Iacopo Sardi
BACKGROUND: The incidence of gemcitabine-induced hemolytic uremic syndrome has already been described in adults. Several approaches have been employed in the treatment of gemcitabine-induced hemolytic uremic syndrome with different outcomes. One of the most promising agents is eculizumab, which is a monoclonal antibody directed against C5 complement protein. CASE PRESENTATION: We reported the case of a 3-year-old white boy with medulloblastoma who underwent high-dose chemotherapy and craniospinal irradiation...
July 27, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28738049/atypical-hemolytic-uremic-syndrome-achieving-positive-patient-outcomes-with-early-diagnosis-and-appropriate-management%C3%A2
#13
Dmitriy Sverdlin, Brenda Peters-Watral
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS), a condition found in adult and pediatric populations, can be idiopathic or acquired as a result of major systemic changes. aHUS presents with a wide array of symptoms that can be attributed to other less dangerous conditions. Because of its complex nature and rare occurrence, it is typically diagnosed in later stages and with multiple organ involvement.
. OBJECTIVES: This article provides an overview of aHUS and available interventions...
August 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28729648/a-haplotype-in-cfh-family-genes-confers-high-risk-of-rare-glomerular-nephropathies
#14
Yin Ding, Weiwei Zhao, Tao Zhang, Hao Qiang, Jianping Lu, Xin Su, Shuzhen Wen, Feng Xu, Mingchao Zhang, Haitao Zhang, Caihong Zeng, Zhihong Liu, Huimei Chen
Despite distinct renal lesions, a series of rare glomerular nephropathies are reportedly mediated by complement overactivation. Genetic variations in complement genes contribute to disease risk, but the relationship of genotype to phenotype has not been straightforward. Here, we screened 11 complement genes from 91 patients with atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G) and membranoproliferative glomerulonephritis type I (MPGN I), and identified the concomitant presence of three missense variations located within the human complement Factor H (CFH) gene cluster...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729035/a-novel-cfhr1-cfhr5-hybrid-leads-to-a-familial-dominant-c3-glomerulopathy
#15
Shambhuprasad K Togarsimalemath, Sidharth K Sethi, Rajan Duggal, Moglie Le Quintrec, Pranaw Jha, Régis Daniel, Florence Gonnet, Shyam Bansal, Lubka T Roumenina, Veronique Fremeaux-Bacchi, Vijay Kher, Marie-Agnes Dragon-Durey
The intrinsic similarity shared between the members of the complement factor H family, which comprises complement factor H and five complement factor H-related (CFHR) genes, leads to various recombination events. In turn these events lead to deletions of some genes or abnormal proteins, which are found in patients with atypical hemolytic uremic syndrome or C3 glomerulopathies. Here we describe a novel genetic rearrangement generated from a heterozygous deletion spanning 146 Kbp involving multiple CFHR genes leading to a CFHR1-R5 hybrid protein...
July 17, 2017: Kidney International
https://www.readbyqxmd.com/read/28726627/mucus-activatable-shiga-toxin-genotype-stx2d-in-escherichia-coli-o157-h7
#16
Sergio Sánchez, María Teresa Llorente, Laura Herrera-León, Raquel Ramiro, Sandra Nebreda, María Antonia Remacha, Silvia Herrera-León
We identified the mucus-activatable Shiga toxin genotype stx2d in the most common hemolytic uremic syndrome-associated Escherichia coli serotype, O157:H7. stx2d was detected in a strain isolated from a 2-year-old boy with bloody diarrhea in Spain, and whole-genome sequencing was used to confirm and fully characterize the strain.
August 2017: Emerging Infectious Diseases
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/28720077/hemolytic-uremic-syndrome-as-the-presenting-manifestation-of-wt1-mutation-and-denys-drash-syndrome-a-case-report
#18
Joseph L Alge, Scott E Wenderfer, John Hicks, Mir Reza Bekheirnia, Deborah A Schady, Jamey S Kain, Michael C Braun
BACKGROUND: Hemolytic uremic syndrome (HUS) can occur as a primary process due to mutations in complement genes or secondary to another underlying disease. HUS sometimes occurs in the setting of glomerular diseases, and it has been described in association with Denys-Drash syndrome (DDS), which is characterized by the triad of abnormal genitourinary development; a pathognomonic glomerulopathy, diffuse mesangial sclerosis; and the development of Wilms tumor. CASE PRESENTATION: We report the case of a 46, XX female infant who presented with HUS and biopsy-proven thrombotic microangiopathy...
July 18, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28718863/nya-rutiner-f%C3%A3-r-smittskydds%C3%A2-%C3%A3-tg%C3%A3-rder-vid-ehec-infektion-endast-ehec-som-b%C3%A3-r-p%C3%A3-stx2-genen-kan-kopplas-till-hus-%C3%A2-dessa-smittb%C3%A3-rare-m%C3%A3-ste-avst%C3%A3-ngas-fr%C3%A3-n-arbete-eller-f%C3%A3-rskola
#19
Peter Nolskog, Bo Svenungsson, Cecilia Jernberg
New regulations concerning EHEC/VTEC Hemolytic Uremic Syndrome (HUS) is the most severe complication to an infection with EHEC (enterohemorrhagic E. coli), also called VTEC (verocytotoxin-producing E. coli). Risk of severe complications such as HUS is an important reason why the Swedish Communicable Diseases Act (Smittskyddslag. 2004:168) includes infection with EHEC. With very few exceptions, only EHEC with the stx2 gene is associated with HUS. According to the law, persons working with unpackaged foods, infants or severely immunocompromised patients, and children attending preschool can be suspended awaiting negative test results for EHEC...
July 12, 2017: Läkartidningen
https://www.readbyqxmd.com/read/28718802/ouabain-protects-human-renal-cells-against-the-cytotoxic-effects-of-shiga-toxin-type-2-and-subtilase-cytotoxin
#20
María M Amaral, Magalí C Girard, Romina S Álvarez, Adrienne W Paton, James C Paton, Horacio A Repetto, Flavia Sacerdoti, Cristina A Ibarra
Hemolytic uremic syndrome (HUS) is one of the most common causes of acute renal failure in children. The majority of cases are associated with Shiga toxin (Stx)-producing Escherichia coli (STEC). In Argentina, HUS is endemic and presents the highest incidence rate in the world. STEC strains expressing Stx type 2 (Stx2) are responsible for the most severe cases of this pathology. Subtilase cytotoxin (SubAB) is another STEC virulence factor that may contribute to HUS pathogenesis. To date, neither a licensed vaccine nor effective therapy for HUS is available for humans...
July 18, 2017: Toxins
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