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J Nephrol 2021 May 6. Epub 2021 May 6.

Kidney Transplant Unit, Center for HUS Prevention, Control and Management, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Rationale And Objective: Patients with atypical hemolytic uremic syndrome (aHUS) have long been considered ineligible for kidney transplantation (KTx) in several centers due to the high risk of disease recurrence, graft loss and life-threatening complications. The availability of Eculizumab (ECU) has now overcome this problem. However, the best approach towards timing, maintenance schedule, the possibility of discontinuation and patient monitoring has not yet been clearly established. Read More

Nat Rev Nephrol 2021 May 5. Epub 2021 May 5.

Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service d'Immunologie, Paris, France.

Studies of complement genetics have changed the landscape of thrombotic microangiopathies (TMAs), particularly atypical haemolytic uraemic syndrome (aHUS). Knowledge of complement genetics paved the way for the design of the first specific treatment for aHUS, eculizumab, and is increasingly being used to aid decisions regarding discontinuation of anti-complement treatment in this setting. Complement genetic studies have also been used to investigate the pathogenic mechanisms that underlie other forms of HUS and provided evidence that contributed to the reclassification of pregnancy- and postpartum-associated HUS within the spectrum of complement-mediated aHUS. Read More

Virulence 2021 Dec;12(1):1296-1305

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

Shiga toxin-producing , a foodborne bacterial pathogen, has been linked to a broad spectrum of clinical outcomes ranging from asymptomatic carriage to fatal hemolytic uremic syndrome (HUS). Here, we collected clinical data and STEC strains from HUS patients from 1994 through 2018, whole-genome sequencing was performed to molecularly characterize HUS-associated STEC strains, statistical analysis was conducted to identify bacterial genetic factors associated with severe outcomes in HUS patients. O157:H7 was the most predominant serotype (57%) among 54 HUS-associated STEC strains, followed by O121:H19 (19%) and O26:H11 (7%). Read More

Kidney Int 2021 Apr 27. Epub 2021 Apr 27.

Department of Immunodynamics, Institute of Experimental Immunology and Imaging, University Hospital Essen, Essen, Germany. Electronic address:

Enterohaemorrhagic E. coli cause major epidemics worldwide with significant organ damage and very high percentages of death. Due to the ability of enterohaemorrhagic E. Read More

Toxins (Basel) 2021 04 26;13(5). Epub 2021 Apr 26.

Centre de Référence des Microangiopathies Thrombotiques (CNR-MAT), Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, 75012 Paris, France.

Shiga toxin-producing -associated hemolytic uremic syndrome (STEC-HUS) is a form of thrombotic microangiopathy secondary to an infection by an enterohemorrhagic . Historically considered a pediatric disease, its presentation has been described as typical, with bloody diarrhea at the forefront. However, in adults, the clinical presentation is more diverse and makes the early diagnosis hazardous. Read More

J Pers Med 2021 Apr 15;11(4). Epub 2021 Apr 15.

Warsaw Genomics INC, 01-682 Warsaw, Poland.

Atypical hemolytic uremic syndrome (aHUS) is a rare disease triggered by dysregulation of the alternative complement pathway, consisting of a characteristic triad of nonimmune hemolytic anemia, thrombocytopenia, and renal failure. The risk of aHUS onset, recurrence, and allograft loss depends on the genetic background of a patient. We show a series of cases from a single family whose five members were affected by aHUS and presented distinct clinical outcomes. Read More

Foods 2021 Apr 10;10(4). Epub 2021 Apr 10.

Public Health Department, College of Public Health and Health Informatics, Ha'il University, Ha'il 2440, Saudi Arabia.

Background: The emergence of multiple antibiotic resistance (MAR) ( and virulent non-O157 Shiga toxin-producing (STEC) poses a growing concern to the meat industry. Non-O157 STEC strains including O26, O45, O103, O111, O121, and O145 have been implicated in the occurrence of bloody diarrhea and hemolytic uremic syndrome in humans. This research assessed prevalence, matrix-assisted laser desorption/ionization-time of flight mass-spectrometry (MALDI-TOF MS) protein mass-spectra profiles, multidrug-resistance traits, polymerase chain reaction detection of virulence, and antibiotic-resistance genes of isolated from beef carcasses and slaughterhouse environments. Read More

Kidney Int Rep 2021 Apr 3;6(4):1099-1109. Epub 2021 Feb 3.

Department of Nephrology and Clinical Immunology.

Introduction: The syndromes of thrombotic microangiopathy (TMA) are diverse and represent severe endothelial damage caused by various mechanisms. The complement system plays a major role in a subset of patients with TMA, and its recognition is of clinical importance because it guides choice and duration of treatment.

Methods: We studied a well-defined cohort of patients with TMA and hypothesized that assessment of serum-induced   C5b9 formation on the endothelium and screening for rare variants in complement genes can better categorize TMA. Read More

J Med Chem 2021 Apr 28. Epub 2021 Apr 28.

Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.

Shiga toxin is an AB toxin produced by species, while related toxins are produced by Shiga toxin-producing (STEC). Infection by Shigella can lead to bloody diarrhea followed by the often fatal hemolytic uremic syndrome (HUS). In the present paper, we aimed for a simple and effective toxin inhibitor by comparing three classes of carbohydrate-based inhibitors: glycodendrimers, glycopolymers, and oligosaccharides. Read More

Emerg Infect Dis 2021 May;27(5):1509-1512

We report a fatal case of hemolytic uremic syndrome with urinary tract infection in Japan caused by Shiga toxin-producing Escherichia coli. We genotypically identified the isolate as OX18:H2. Whole-genome sequencing revealed 3 potentially pathogenic lineages (OX18:H2, H19, and H34) that have been continuously isolated in Japan. Read More

Front Med (Lausanne) 2021 8;8:642864. Epub 2021 Apr 8.

Nephrology Department, University Hospital Dr. Peset, Valencia, Spain.

Thrombotic microangiopathy is a rare but serious complication that affects kidney transplant recipients. It appears in 0.8-14% of transplanted patients and negatively affects graft and patient survival. Read More

Clin Nephrol 2021 Apr 26. Epub 2021 Apr 26.

Background: Bevacizumab is a recombinant monoclonal antibody against the vascular endothelial growth factor A (VEGF-A) ligand that is used in the management of various solid malignancies. The adverse effect profiles of angiogenesis inhibitors, such as bevacizumab, have become increasingly well characterized and include renal manifestations such as hypertension, proteinuria, and thrombotic microangiopathy. Eculizumab inhibits terminal-complement activation and is used to treat atypical hemolytic uremic syndrome. Read More

J Comp Pathol 2021 Apr 8;184:95-100. Epub 2021 Apr 8.

Anderson Moores Veterinary Specialists, Hursley, Winchester, UK.

Cutaneous and renal glomerular vasculopathy (CRGV) is an emerging disease in the UK, but its aetiology remains unclear. It is considered a thrombotic microangiopathy (TMA) in which the kidney and skin are the most commonly affected organs. We now document two cases of CRGV with brain lesions, which may have accounted for neurological signs displayed by these animals. Read More

Kidney Int 2021 May;99(5):1244

Clin Nephrol Case Stud 2021 16;9:45-48. Epub 2021 Apr 16.

Pediatric Nephrology, Dialysis, and Transplantation Department of Woman and Child Health, University of Padova, Padova.

A 3-year-old girl came to our attention for fever and upper respiratory tract infection associated with thrombocytopenia, non-immune hemolytic anemia, and acute kidney injury (AKI). Complete blood count and renal function slowly normalized, with no need for dialysis. She was always normotensive with valid diuresis; her neurological status also rapidly improved. Read More

J Pediatr Intensive Care 2021 Jun 20;10(2):106-109. Epub 2020 Jul 20.

Department of Pediatric Intensive Care, Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Therapeutic plasma exchange (TPE) is a treatment administered with the aim of removing a pathogenic material or compound causing morbidity in a variety of neurologic, hematologic, renal, and autoimmune diseases. In this study, we aimed to assess the indications, efficacy, reliability, complications, and treatment response of pediatric patients for TPE. This retrospective study analyzed data from 39 patients aged from 0 to 18 years who underwent a total of 172 TPE sessions from January 2015 to April 2018 in a tertiary pediatric intensive care unit. Read More

Sci Rep 2021 Apr 21;11(1):8601. Epub 2021 Apr 21.

Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, 66506, USA.

Shiga toxin-producing Escherichia coli (STEC) are foodborne pathogens that cause illnesses in humans ranging from mild to hemorrhagic enteritis with complications of hemolytic uremic syndrome and even death. Cattle are a major reservoir of STEC, which reside in the hindgut and are shed in the feces, a major source of food and water contaminations. Seven serogroups, O26, O45, O103, O111, O121, O145 and O157, called 'top-7', are responsible for the majority of human STEC infections in North America. Read More

BMC Nephrol 2021 Apr 20;22(1):140. Epub 2021 Apr 20.

Department Paediatric Nephrology, King Abdullah Specialists Children Hospital, Riyadh, Saudi Arabia.

Background: Atypical haemolytic uraemic syndrome (aHUS) is a rare systemic syndrome characterized by non-immune haemolytic anaemia, thrombocytopenia, and kidney injury. In most cases, alternative complement pathway dysregulation is the identifying cause. Recently, other genetic causes have been identified, including a mutation in the diacylglycerol kinase epsilon (DGKE) gene, which theoretically affect the coagulation pathway and does not affect the complement pathway. Read More

Nephron 2021 Apr 19:1-13. Epub 2021 Apr 19.

Department of Nephrology, Beijing Children's Hospital, Capital Medical University, Beijing, China.

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare but critical illness. To this date, few studies have reported on the disease in Chinese children.

Methods: We studied a Chinese pediatric cohort to delineate the clinical characteristics, genotypes, and prognosis. Read More

Drugs 2021 Apr;81(6):737

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

Can J Kidney Health Dis 2021 31;8:20543581211003763. Epub 2021 Mar 31.

Nephrology Service, Walter Reed National Military Medical Center, Bethesda, MD, USA.

Introduction: Among kidney transplant recipients (KTRs) with end-stage kidney disease (ESKD) due to atypical hemolytic uremic syndrome (aHUS), recurrence is associated with poor allograft outcomes. We compared graft and patient survival of aHUS KTRs with and without prophylactic/early use of eculizumab, a monoclonal antibody that binds complement protein C5, at the time of transplantation.

Methods: We conducted a retrospective cohort study using the United States Renal Data System. Read More

Epidemiol Infect 2021 Apr 19;149:e108. Epub 2021 Apr 19.

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

Recurrent outbreaks of haemolytic uraemic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) serotype O55:H7 occurred in England between 2014 and 2018. We reviewed the epidemiological evidence to identify potential source(s) and transmission routes of the pathogen, and to assess the on-going risk to public health. Over the 5-year period, there were 43 confirmed and three probable cases of STEC O55:H7. Read More

Ann Clin Microbiol Antimicrob 2021 Apr 15;20(1):24. Epub 2021 Apr 15.

Molecular Biology Department, Pasteur Institute of Iran, Tehran, Iran.

Background: Shiga toxin-producing Escherichia coli (STEC) are among common foodborne bacterial pathogens and healthy livestock are the main source of this bacterium. Severe diseases attribute to two types of cytotoxin Stx1 and Stx2, which are also called Shiga toxin (Stx). Infection of humans with STEC may result in Acute diarrhea with or without bleeding, hemorrhagic colitis (HC) and the hemolytic uremic syndrome (HUS). Read More

Acad Pathol 2021 Jan-Dec;8:23742895211001312. Epub 2021 Mar 30.

Robert J. Tomsich Department of Pathology and Laboratory Medicine, Cleveland Clinic Foundation, OH, USA.

http://journals.sagepub.com/doi/10. Read More

Methods Mol Biol 2021 ;2227:133-139

Clinic of Nephrology, University Hospital-"Tzaritza Yoanna-ISUL", Medical University of Sofia, Sofia, Bulgaria.

Autoantibodies against complement proteins are involved in the pathological process of many diseases, including lupus nephritis, C3 glomerulopathies, and atypical hemolytic uremic syndrome. This method describes the detection of autoantibodies targeting the central complement component C3 by ELISA. These autoantibodies (IgG) are detected in up to 30% of the patients with lupus nephritis and more rarely in cases with C3 glomerulopathies. Read More

Methods Mol Biol 2021 ;2227:97-105

Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Paris, France.

The three pathways of the complement system converge toward the cleavage of the central complement component C3 into its activated fragments, with C3b being able to bind covalently to the activating surface. The endothelial cells are among the major targets for complement attack in pathological conditions, as the atypical hemolytic uremic syndrome. Therefore, study of complement C3 deposition on endothelial cells by flow cytometry is a sensitive test to measure complement activation. Read More

Methods Mol Biol 2021 ;2227:83-96

Department of Pediatric Nephrology, Radboud Institute for Molecular Life Sciences, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.

The complement system is a key part of innate immunity. However, if the system becomes dysregulated, damage to healthy host cells can occur, especially to the glomerular cells of the kidney. The convertases of the alternative pathway of the complement system play a crucial role in complement activation. Read More

Methods Mol Biol 2021 ;2227:69-81

INSERM, UMRS 1138, "Inflammation, Complement and Cancer" Team, Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, Paris, France.

Impairment of the complement regulatory protein Factor H (FH) is implicated in the physiopathological mechanisms of different diseases like atypical hemolytic and uremic syndrome and C3 glomerulopathies. It may be due to genetic abnormalities or acquired with the development of autoantibodies. FH has several ligands; therefore, the exploration of its functions requires to perform different tests. Read More

Methods Mol Biol 2021 ;2227:1-20

INSERM, UMRS 1138, Inflammation, Complement and Cancer Team, Centre de Recherche des Cordelier, Sorbonne Universités, Université de Paris, Paris, France.

The complement cascade is an evolutionary ancient innate immune defense system, playing a major role in the defense against infections. Its function in maintaining host homeostasis on activated cells has been emphasized by the crucial role of its overactivation in ever growing number of diseases, such as atypical hemolytic uremic syndrome (aHUS), autoimmune diseases as systemic lupus erythematosus (SLE), C3 glomerulopathies (C3GN), age-related macular degeneration (AMD), graft rejection, Alzheimer disease, and cancer, to name just a few. The last decade of research on complement has extended its implication in many pathological processes, offering new insights to potential therapeutic targets and asserting the necessity of reliable, sensitive, specific, accurate, and reproducible biomarkers to decipher complement role in pathology. Read More

Clin Kidney J 2021 Apr 20;14(4):1255-1260. Epub 2020 Aug 20.

Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.

Background: Pregnancies in patients with complement gene variant-mediated thrombotic microangiopathy (cTMA) are challenging, and pregnancies in such patients after kidney transplantation (KTX) are even more so.

Methods: We identified nine pregnancies following KTX of three genetically high-risk cTMA patients enrolled in the Vienna thrombotic microangiopathy cohort. Preventive plasma therapy was used in three pregnancies, and one patient had ongoing eculizumab (ECU) therapy during two pregnancies. Read More