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J Med Chem 2019 Apr 17. Epub 2019 Apr 17.

Complement Factor D (FD), a highly specific S1 serine protease, plays a central role in the amplification of the alternative complement pathway (AP) of the innate immune system. Dysregulation of AP activity predisposes individuals to diverse disorders such as age-related macular degeneration (AMD), atypical hemolytic uremic syndrome (aHUS), membranoproliferative glomerulonephritis type II (MPGNII) and paroxysmal nocturnal hemoglobinuria (PNH). Previously, we have reported the screening efforts and identification of reversible benzylamine-based FD inhibitors (1 and 2) binding to the open active conformation of FD. Read More

J Med Microbiol 2019 Apr 17. Epub 2019 Apr 17.

4 Field Services, National Infection Service, Public Health England, London, UK.

Purpose: This study describes the epidemiology of Shiga toxin-producing Escherichia coli (STEC) infections in a population in the South East of England.

Methods: From 1 November 2013 to 31 March 2017 participating diagnostic laboratories reported Shiga toxin gene (stx) positive real-time PCR results to local public health teams. Stx positive faecal samples/isolates were referred to the Gastrointestinal Bacteria Reference Unit (GBRU) for confirmation by culture and typing by whole genome sequencing (WGS). Read More

Pediatr Nephrol 2019 Apr 15. Epub 2019 Apr 15.

Laboratory of Immunology, Hopital Europeen Georges Pompidou, INSERM UMRS 1138, Paris Descartes University, Paris, France.

Background: Hemolytic uremic syndrome (HUS) is a leading cause of acute kidney injury in children. Although international guidelines emphasize comprehensive evaluation and treatment with eculizumab, access to diagnostic and therapeutic facilities is limited in most developing countries. The burden of Shiga toxin-associated HUS in India is unclear; school-going children show high prevalence of anti-factor H (FH) antibodies. Read More

Rev Prat 2019 Mar;69(3):336-340

UMR BIPAR, Ecole nationale vétérinaire d'Alfort, Anses, INRA, université Paris-Est, Maisons- Alfort, France.

Zoonoses related to leisure activities. Many zoonoses can be contracted by humans during recreational activities. In the context of a walk, some of them, such as Lyme disease, are transmissible by biological vectors, particularly ticks, or by aerosol (Q fever, hantavirose), whereas others can be contracted in case of aquatic activities (leptospirosis), hunting (tularaemia), and visits to pet farms or fairs (especially the hemolytic uremic syndrome). Read More

G Ital Nefrol 2019 Apr;36(2)

Centro per la Cura e lo Studio della Sindrome Emolitico-Uremica. Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano.

Thrombotic microangiopathies (TMA) are a group of diseases that can complicate pregnancy and threaten the lives of both the mother and the fetus. Several conditions can lead to TMA, including thrombotic thrombocytopenic purpura (TTP), HELLP syndrome and hemolytic uremic syndrome (HUS). We describe the case of a 39-year-old woman who presented a HELLP syndrome in the immediate postpartum period. Read More

Kidney Int 2019 Mar 15. Epub 2019 Mar 15.

Centre de Recherche en Transplantation et Immunologie, UMR 1064, INSERM, Université de Nantes, Nantes, France; Institut de Transplantation Urologie Néphrologie, CHU Nantes, Nantes, France; Department of Nephrology and Immunology, Center Hospitalier Universitaire de Nantes, Nantes, France. Electronic address:

Secondary hemolytic uremic syndrome (HUS) is a heterogeneous group of thrombotic microangiopathies associated with various underlying conditions. Whether it belongs to the spectrum of complement-mediated HUS remains controversial. We analysed the presentation, outcome, and frequency of complement gene rare variants in a cohort of 110 patients with secondary HUS attributed to drugs (29%), autoimmune diseases (24%), infections (17%), malignancies (10%), glomerulopathies (9%), extra-renal organ transplantation (8%), and pancreatitis (3%). Read More

Thromb Res 2019 Mar 28;178:54-58. Epub 2019 Mar 28.

Deaprtment of Molecular and Laboratory Medicine, Mie University Hospital and Mie University Graduate School of Medicine, Tsu, Japan. Electronic address:

Background: Thrombotic microangiopathy (TMA) is caused by activated platelets. The plasma C-type lectin-like receptor 2 (CLEC2) levels in 58 patients with TMA were examined and compared with those in healthy volunteers and other diseases.

Materials And Methods: The plasma levels of soluble platelet surface glycoprotein VI (GPVI) and CLEC2 were measured in patients with TMA. Read More

Clin Kidney J 2019 Apr 16;12(2):196-205. Epub 2018 May 16.

Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

Background: Eculizumab, a terminal complement inhibitor, is approved for atypical haemolytic uraemic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA).

Methods: In five parent studies, eculizumab effectively prevented TMA and improved renal and haematologic outcomes in patients with aHUS; therefore, these patients could enrol in this long-term, prospective, observational and multicentre study. The primary endpoint was the TMA manifestation rate off and on eculizumab post-parent study. Read More

BMC Nephrol 2019 Apr 10;20(1):125. Epub 2019 Apr 10.

Division of Pediatric Nephrology, Emory University School of Medicine and Children's Healthcare of Atlanta, 2015 Uppergate Drive NE, Atlanta, GA, 30322, USA.

Background: There are limited long-term outcome data in eculizumab-treated patients with atypical hemolytic uremic syndrome (aHUS). We report final results from the largest prospective, observational, multicenter study of patients with aHUS treated with eculizumab.

Methods: Patients with aHUS who participated in any of five parent eculizumab trials and received at least one eculizumab infusion were eligible for enrollment in a long-term follow-up study. Read More

Toxins (Basel) 2019 Apr 9;11(4). Epub 2019 Apr 9.

Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USA.

species and Shiga toxin-producing (STEC) are agents of bloody diarrhea that may progress to potentially lethal complications such as diarrhea-associated hemolytic uremic syndrome (D+HUS) and neurological disorders. The bacteria share the ability to produce virulence factors called Shiga toxins (Stxs). Research over the past two decades has identified Stxs as multifunctional toxins capable of inducing cell stress responses in addition to their canonical ribotoxic function inhibiting protein synthesis. Read More

Kidney Res Clin Pract 2019 Apr 11. Epub 2019 Apr 11.

Department of Internal Medicine, Mediplex Sejong Hospital, Incheon, Korea.

SAGE Open Med Case Rep 2019 1;7:2050313X19839531. Epub 2019 Apr 1.

Department of Medicine, Weill Cornell Medicine/New York-Presbyterian Hospital, New York, NY, USA.

In this clinical vignette, we present a case of a 59-year-old woman with catastrophic antiphospholipid syndrome likely triggered by polymicrobial sepsis. The diagnostic criteria and clinical manifestations of catastrophic antiphospholipid syndrome are reviewed. We also compare diagnostic criteria and clinical manifestations with other clinical entities in the differential diagnosis, including thrombotic thrombocytopenic purpura-hemolytic-uremic syndrome, disseminated intravascular coagulation, sepsis, and inflammatory bowel disease. Read More

Pediatr Nephrol 2019 Apr 8. Epub 2019 Apr 8.

Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, 59 Boulevard Pinel, 69677, Bron, France.

Background: Liver lesions of hemolytic uremic syndrome due to Shiga-toxin-producing Escherichia coli (STEC-HUS) are uncommon.

Case-diagnosis/treatment: We report three observations of severe STEC-HUS with delayed hepatic involvement. They presented with multiple organ failure and received eculizumab; 15 days after the onset of STEC-HUS, cholestasis appeared and cytolysis worsened. Read More

BMJ Case Rep 2019 Apr 8;12(4). Epub 2019 Apr 8.

Department of Medical Oncology, Saint John of God Hospital Subiaco, Subiaco, Western Australia, Australia.

A woman in her mid-70s with metastatic pancreatic adenocarcinoma presented with fatigue, nausea and bilateral leg swelling, 4 days after an intravenous gemcitabine infusion. Additional examination and laboratory tests showed mild hypertension, low haemoglobin, high lactate dehydrogenase, low platelet count and high serum creatinine. The patient was subsequently diagnosed with haemolytic uraemic syndrome (HUS), and gemcitabine administration was immediately ceased. Read More

Sci Rep 2019 Apr 4;9(1):5619. Epub 2019 Apr 4.

Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.

Hybrid E. coli pathotypes are representing emerging public health threats with enhanced virulence from different pathotypes. Hybrids of Shiga toxin-producing and enterotoxigenic E. Read More

J Allergy Clin Immunol Pract 2019 Apr 1. Epub 2019 Apr 1.

Department of Pediatrics, Division of Allergy, Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.

Inflamm Bowel Dis 2019 04 1. Epub 2019 Apr 1.

NESMOS Department, Faculty of Medicine & Psychology, Sapienza University of Rome, Sant'Andrea University Hospital, Rome, Italy.

PLoS One 2019 1;14(4):e0214620. Epub 2019 Apr 1.

Division of Microbiology, Center for Food Safety and Applied Nutrition, Food and Drug Administration, College Park, MD, United States of America.

Illnesses caused by Shiga toxin-producing Escherichia coli (STECs) can be life threatening, such as hemolytic uremic syndrome (HUS). The STECs most frequently identified by USDA's Microbiological Data Program (MDP) carried toxin gene subtypes stx1a and/or stx2a. Here we described the genome sequences of 331 STECs isolated from foods regulated by the FDA 2010-2017, and determined their genomic identity, serotype, sequence type, virulence potential, and prevalence of antimicrobial resistance. Read More

J Pediatr Hematol Oncol 2019 Mar 29. Epub 2019 Mar 29.

Pediatric Nephrology, Cliniques Universitaires St. Luc (UCL), Brussels, Belgium.

Typical hemolytic uremic syndrome (HUS) in children is caused mostly by Escherichia coli 0157:H7 in our country. Atypical HUS (aHUS) causes include Streptococcus pneumoniae, methyl malonic aciduria, deficiency of ADAMST 13, and genetic or acquired disorder of the complement. Treatment of HUS relies on supportive measures while treatment of aHUS includes plasmapheresis and specific treatments. Read More

Proc Natl Acad Sci U S A 2019 Apr 29;116(16):7926-7931. Epub 2019 Mar 29.

Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH-4056 Basel, Switzerland;

Dysregulation of the alternative complement pathway (AP) predisposes individuals to a number of diseases including paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, and C3 glomerulopathy. Moreover, glomerular Ig deposits can lead to complement-driven nephropathies. Here we describe the discovery of a highly potent, reversible, and selective small-molecule inhibitor of factor B, a serine protease that drives the central amplification loop of the AP. Read More

Emerg Microbes Infect 2019 ;8(1):486-502

a Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile , Santiago , Chile.

Shiga toxin-producing Escherichia coli (STEC) are foodborne pathogens causing severe gastroenteritis, which may lead to hemolytic uremic syndrome. The Locus of Enterocyte Effacement (LEE), a Pathogenicity Island (PAI), is a major determinant of intestinal epithelium attachment of a group of STEC strains; however, the virulence repertoire of STEC strains lacking LEE, has not been fully characterized. The incidence of LEE-negative STEC strains has increased in several countries, highlighting the relevance of their study. Read More

Br J Haematol 2019 Mar 27. Epub 2019 Mar 27.

Department of Haematology, UCLH, Cardiometabolic programme- NIHR UCLH/UCL BRC, London, UK.

The complement inhibitor, eculizumab, has revolutionised the management of atypical haemolytic uraemic syndrome (aHUS), although the optimum treatment duration is debated. Twenty-two cases of acute aHUS managed with eculizumab were retrospectively reviewed, including outcomes after eculizumab withdrawal. Although 41% had an associated complement genetic abnormality, mutation status did not affect severity of clinical presentation. Read More

Kidney Int 2019 Feb 27. Epub 2019 Feb 27.

Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Electronic address:

Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) caused by dysregulated complement activation. Clinically, aHUS is effectively treated by an anti-C5 monoclonal antibody (mAb) but whether the disease is mediated by the C5a receptor (C5aR) or C5b-9 pathway, or both, is unknown. Here we address this in a factor H mutant mouse (FH) which developed complement-mediated TMA as well as macrovascular thrombosis caused by an aHUS-related factor H point mutation (mouse W1206R, corresponding to human W1183R). Read More

J Clin Med 2019 Mar 24;8(3). Epub 2019 Mar 24.

Department of Obstetrics and Gynecology, Helsinki University and Helsinki University Hospital, Haartmaninkatu 2, 00290 Helsinki, Finland.

Excessive complement activation is involved in the pathogenesis of many diseases and the kidney is an organ with particular susceptibility to complement-mediated injury. Apart from paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), there are several other diseases with clear evidence of complement activation affecting both maternal and fetal kidneys during pregnancy and causing long-term adverse outcomes. Several novel drugs have been recently developed for blocking the complement cascade, including purified plasma proteins, new monoclonal antibodies, recombinant proteins, small molecules, and small interfering RNA agents. Read More

Biomed Rep 2019 Mar 7;10(3):175-182. Epub 2019 Feb 7.

Department of Animal Microbiology, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 980-8577, Japan.

Enterohemorrhagic (EHEC) O157:H7 has been known to cause outbreaks of hemorrhagic colitis and hemolytic uremic syndrome. We previously demonstrated that intestinal flora contribute to the prevention of EHEC infection in a mouse model. However, it has not yet been determined whether , a predominant genus in the human intestine, contributes to the prevention of EHEC infection. Read More

Clin Chim Acta 2019 Mar 21;494:143-150. Epub 2019 Mar 21.

Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. Electronic address:

Although atypical hemolytic uremic syndrome (aHUS) is a genetic disorder, molecular defects are detected in only 60% of patients. We aim to dissect the genetic background by whole exome sequence and the clinical characteristics of pediatric patients with aHUS. Ten patients (6 male and 4 female) with mean age 5. Read More

Kidney Int Rep 2019 Mar 3;4(3):434-446. Epub 2018 Dec 3.

Columbia University Medical Center, New York, New York, USA.

Introduction: Recurrence of atypical hemolytic uremic syndrome (aHUS) in renal allografts is common, leading to dialysis and graft failure. Pretransplant versus posttransplant initiation of eculizumab treatment in patients with aHUS has not been rigorously investigated. We hypothesized eculizumab pretransplant would reduce dialysis incidence posttransplant. Read More

Kidney Int Rep 2019 Mar 28;4(3):420-424. Epub 2018 Nov 28.

The George Institute for Global Health, New Delhi, India.

Introduction: Pregnancy-related acute kidney injury is the most common cause of renal cortical necrosis (RCN). Atypical hemolytic uremic syndrome (aHUS) as a cause of RCN in pregnant/postpartum is underevaluated. In the current article, we describe a series of cases of pregnancy-related RCN. Read More

Front Immunol 2019 27;10:337. Epub 2019 Feb 27.

Division of Biodiagnostic Sciences and Technologies, INRASTES, National Center for Scientific Research Demokritos, Athens, Greece.

Thrombotic microangiopathies (TMAs) are a heterogeneous group of syndromes presenting with a distinct clinical triad: microangiopathic hemolytic anemia, thrombocytopenia, and organ damage. We currently recognize two major entities with distinct pathophysiology: thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Beyond them, differential diagnosis also includes TMAs associated with underlying conditions, such as drugs, malignancy, infections, scleroderma-associated renal crisis, systemic lupus erythematosus (SLE), malignant hypertension, transplantation, HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), and disseminated intravascular coagulation (DIC). Read More

Haematologica 2019 Mar 19. Epub 2019 Mar 19.

APHP, Hôpital Européen Georges Pompidou, laboratoire d'Immunologie, INSERM, UMR_S 1138.

Atypical hemolytic uremic syndrome is a prototypic thrombotic microangiopathy attributable to complement dysregulation. Hypertensive emergency, characterized by elevation of systolic (>180mmHg) or diastolic (>120mmHg) blood pressure together with end-organ damage, can cause thrombotic microangiopathy which may mimic atypical hemolytic uremic syndrome. We sought to retrospectively evaluate the clinical, biological and complement genetic characteristics of 76 and 61 atypical hemolytic uremic syndrome patients with and without hypertensive emergency, respectively. Read More

Nephron 2019 Mar 19:1-7. Epub 2019 Mar 19.

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy.

A 6-month-old boy presented with acute renal failure, thrombocytopenia, and severe non-immune hemolytic anemia. Infection by Shiga-like toxin-producing Escherichia coli and other causes of microangiopathic hemolysis were ruled out, leading to a diagnosis of atypical hemolytic uremic syndrome (aHUS). Neither pathogenic variants in HUS-associated genes nor anti-factor H antibodies were identified. Read More

Nephron 2019 Mar 14:1-5. Epub 2019 Mar 14.

Department of Nephrology and Clinical Immunology, Maastricht University Medical Center, Maastricht, The Netherlands,

Severe hypertension can lead to irreversible kidney failure and end-stage renal disease (ESRD) and vice versa. Patients are often classified as hypertensive ESRD with no confirmative proof and the true cause of disease can therefore be missed, affecting outcomes. We present a case of chronic thrombotic microangiopathy (TMA) after kidney transplantation in a recipient who had been classified as hypertensive ESRD and found to have a genetic defect in CD46, a transmembrane protein that regulates complement activation, indicating atypical hemolytic uremic syndrome (HUS). Read More

Anasthesiol Intensivmed Notfallmed Schmerzther 2019 Mar 13;54(3):194-205. Epub 2019 Mar 13.

Nowadays, management of hemotherapy is regulated in Germany by the transfusion act and several guidelines while the transfusing physician is responsible for correct implementation at the bedside. Indications for blood products have to be carefully adapted to the patient's current clinical situation and pre-existing diseases have to be considered as well. Today, for most perioperative elective surgeries, evidence-based transfusion thresholds for packed red blood cell concentrates (RBC) have been defined and should be considered. Read More

Curr Opin Nephrol Hypertens 2019 May;28(3):278-287

Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Cedars Sinai Medical Center, Los Angeles, California, USA.

Purpose Of Review: Atypical hemolytic uremic syndrome (aHUS) is a diagnosis that has captured the interest of specialists across multiple fields. The hallmark features of aHUS are microangiopathic hemolysis and thrombocytopenia, which creates a diagnostic dilemma because of the occurrence of these findings in a wide variety of clinical disorders.

Recent Findings: In most of the instances, aHUS is a diagnosis of exclusion after ruling out causes such as Shigella toxin, acquired or genetic a disintegrin and metalloproteinase thrombospondin motif 13 deficiency (thrombotic thrombocytopenic purpura), and vitamin B12 deficiency. Read More

Methods Mol Biol 2019 ;1954:187-202

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.

Escherichia coli serotype O104:H4 (ECO104) is a potent intestinal pathogen that causes severe bloody diarrhea and hemolytic-uremic syndrome. The O antigenic polysaccharides of ECO104 consist of repeating units with the structure [4Galα1-4Neu5,7,9Ac3α2-3Galβ1-3GalNAcβ1-]. These repeating units are assembled sequentially by specific glycosyltransferases on a diphosphate-undecaprenol intermediate. Read More

Clin J Am Soc Nephrol 2019 Apr 12;14(4):557-566. Epub 2019 Mar 12.

Service de Néphrologie-hypertension, Dialyses, Transplantation Rénale, Hôpital Bretonneau et hôpital Clocheville,

Background And Objectives: Thrombotic microangiopathies constitute a diagnostic and therapeutic challenge. Secondary thrombotic microangiopathies are less characterized than primary thrombotic microangiopathies (thrombotic thrombocytopenic purpura and atypical hemolytic and uremic syndrome). The relative frequencies and outcomes of secondary and primary thrombotic microangiopathies are unknown. Read More

Front Immunol 2019 25;10:240. Epub 2019 Feb 25.

Research Laboratory, MTA-SE Research Group of Immunology and Hematology, 3rd Department of Internal Medicine, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.

Pentraxin-3 (PTX3) and C-reactive protein (CRP) have been shown to regulate complement activation , but their role has not been investigated in complement consumption . Thrombotic microangiopathies (TMA) are often accompanied by complement overactivation and consumption, therefore we analyzed the relation of the systemic pentraxin levels to the complement profile, laboratory parameters and clinical outcome of TMA patients. We determined the PTX3 and CRP levels, complement factor and activation product concentrations in blood samples of 171 subjects with the diagnosis of typical hemolytic uremic syndrome (STEC-HUS) ( = 34), atypical HUS (aHUS) ( = 44), secondary TMA ( = 63), thrombotic thrombocytopenic purpura (TTP) ( = 30) and 69 age-matched healthy individuals. Read More

Am J Kidney Dis 2019 Mar 6. Epub 2019 Mar 6.

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Clinical Research Center for Rare Diseases Aldo e Cele Daccò and Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy; L. Sacco Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.

Rationale & Objective: Although primary atypical hemolytic uremic syndrome (aHUS) is associated with abnormalities in complement genes and antibodies to complement factor H, the role of complement in secondary aHUS remains debatable. We evaluated the usefulness of an ex vivo test to: (1) detect complement activation within the endothelium in primary and secondary aHUS, (2) differentiate active disease from remission, (3) monitor the effectiveness of eculizumab therapy, and (4) identify relapses during eculizumab dosage tapering and after discontinuation of treatment.

Study Design: Case series. Read More

Iran J Kidney Dis 2019 Jan;13(1):32-35

Department of Pediatrics, Iran University of Medical and Sciences, Tehran, Iran.

Introduction: Central nervous system (CNS) involvement is the most common extrarenal involvement in hemolytic uremic syndrome (HUS). There are limited reports on clinical cause of chronic neurologic problems in HUS. We evaluated residual neurologic involvement in children with HUS. Read More

Eur J Ophthalmol 2019 Mar 6:1120672119833277. Epub 2019 Mar 6.

Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain.

Purpose:: To report a case of Purtscher-like retinopathy due to atypical hemolytic uremic syndrome and the changes seen in the optical coherence tomography angiography before and after treatment with eculizumab.

Case Description:: A 22-year-old man with an unremarkable medical history presented with acute, bilateral blurred vision and headache of 1-week duration. Best corrected visual acuity of 20/50 and 20/40, respectively, in the patient's right eye and left eye. Read More

J Emerg Med 2019 Apr 27;56(4):441-443. Epub 2019 Feb 27.

Geisel School of Medicine at Dartmouth, Hanover, New Hampshire and Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire.

Background: Atypical hemolytic uremic syndrome (aHUS) is a complement-mediated disease manifesting in thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury. It has a higher incidence of extrarenal manifestations, including central nervous system findings like seizure or stroke, pancreatitis, and cardiac manifestations.

Case Report: We present a case of an unimmunized 14-month-old girl presenting with generalized seizure and ultimately diagnosed with aHUS. Read More

Med Arch 2018 Dec;72(6):453-455

Clinic of Hemodialysis, Clinical Center University of Sarajevo, Bosnia and Herzegovina.

Introduction: Plasmapheresis is often used as a therapy in the treatment of thrombotic thrombocytopenic purpura (TTP). TTP is manifested in thrombotic microangiopathy, consumed thrombocytopenia, hemolytic anemia and acute kidney injury with HUS development, neurologic dysfunction, and fever.

Case Report: we will present a case of a patient with acute kidney injury and refractory TTP at the beginning of hospitalization, subsequently manifested in secondary nephrotic syndrome. Read More

Euro Surveill 2019 Feb;24(8)

Members of the Réseau français hospitalier de surveillance du SHU pédiatrique have been listed at the end of the article.

IntroductionHaemolytic uraemic syndrome (HUS) related to Shiga toxin-producing (STEC) is the leading cause of acute renal failure in young children. In France, HUS surveillance in children aged < 15 years was implemented starting from 1996.AimWe present the results of this surveillance between 2007 and 2016. Read More

Saudi J Kidney Dis Transpl 2019 Jan-Feb;30(1):194-201

Department of Nephrology, The Kidney Centre Postgraduate Training Institute, Karachi, Pakistan.

Acute kidney injury (AKI) in pregnancy is associated with significant maternal morbidity and mortality. Several studies from worldwide have shown different frequencies of the causes of pregnancy-related AKI (PRAKI). The present study aimed to provide local data on frequency of causes of PRAKI. Read More

Blood Adv 2019 Feb;3(4):621-632

Department of Immunopathology, Sanquin Research, and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Mutations in the gene encoding for complement regulator factor H (FH) severely disrupt its normal function to protect human cells from unwanted complement activation, resulting in diseases such as atypical hemolytic uremic syndrome (aHUS). aHUS presents with severe hemolytic anemia, thrombocytopenia, and renal disease, leading to end-stage renal failure. Treatment of severe complement-mediated disease, such as aHUS, by inhibiting the terminal complement pathway, has proven to be successful but at the same time fails to preserve the protective role of complement against pathogens. Read More

Nefrologia 2019 Feb 21. Epub 2019 Feb 21.

Servicio de Nefrología, Hospital Universitario Puerta del Mar, Cádiz, España.

Cureus 2018 Dec 8;10(12):e3706. Epub 2018 Dec 8.

Hematology, Thomas Jefferson University Hospital, Philadelphia, USA.

Spontaneous tumor lysis syndrome is an exceedingly rare manifestation of metastatic prostate cancer. It can masquerade as thrombotic thrombocytopenic purpura (TTP) or complement-mediated hemolytic uremic syndrome (HUS). These entities present with microangiopathic hemolytic anemia, thrombocytopenia, and renal failure, and improve with the initiation of plasma exchange and steroids. Read More

Br J Haematol 2019 Apr 15;185(2):297-310. Epub 2019 Feb 15.

Hannover Medical School, Hannover, Germany.

Eculizumab is the first and only medication approved for paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS) treatment. However, eculizumab safety based on long-term pharmacovigilance is unknown. This analysis summarises safety data collected from spontaneous and solicited sources from 16 March 2007 through 1 October 2016. Read More

Drugs 2019 Feb;79(3):347-352

Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.

Ravulizumab (ravulizumab-cwvz; ULTOMIRIS™), a humanized monoclonal antibody, is a complement C5 inhibitor developed by Alexion Pharmaceuticals for the treatment of paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS). Like the first-generation C5 inhibitor, eculizumab, ravulizumab binds specifically and with high affinity to the complement protein C5, thereby preventing formation of the terminal complement complex C5b-9, which mediates cell lysis. In December 2018, intravenous ravulizumab received its first global approval in the USA for the treatment of adults with PNH, and is under regulatory review in the European Union and Japan in this indication. Read More

Clin Pharmacokinet 2019 Feb 13. Epub 2019 Feb 13.

Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.

Eculizumab is the first drug approved for the treatment of complement-mediated diseases, and current dosage schedules result in large interindividual drug concentrations. This review provides insight into the pharmacokinetic and pharmacodynamic properties of eculizumab, both for reported on-label (paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia gravis) and off-label (hematopoietic stem cell transplantation-associated thrombotic microangiopathy) indications. Furthermore, we discuss the potential of therapeutic drug monitoring to individualize treatment and reduce costs. Read More