Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study.

The optimal duration of eculizumab treatment in patients with atypical hemolytic uremic syndrome (aHUS) remains poorly defined. We conducted a prospective national multicenter open-label study to assess eculizumab discontinuation in children and adults with aHUS. Fifty-five patients (including 19 children) discontinued eculizumab (mean treatment duration, 16.

Management of thrombotic microangiopathy in pregnancy and postpartum: report from an international working group.

Pregnancy and postpartum are high-risk periods for different forms of thrombotic microangiopathy (TMA). However, the management of pregnancy-associated TMA remains ill defined. This report, by an international multidisciplinary working group of obstetricians, nephrologists, hematologists, intensivists, neonatologists, and complement biologists, summarizes the current knowledge of these potentially severe disorders and proposes a practical clinical approach to diagnose and manage an episode of pregnancy-associated TMA.

Use of Highly Individualized Complement Blockade Has Revolutionized Clinical Outcomes after Kidney Transplantation and Renal Epidemiology of Atypical Hemolytic Uremic Syndrome.

Background: Atypical hemolytic uremic syndrome (HUS) is associated with high recurrence rates after kidney transplant, with devastating outcomes. In late 2011, experts in France recommended the use of highly individualized complement blockade-based prophylaxis with eculizumab to prevent post-transplant atypical HUS recurrence throughout the country.

Methods: To evaluate this strategy's effect on kidney transplant prognosis, we conducted a retrospective multicenter study from a large French nationwide registry, enrolling all adult patients with atypical HUS who had undergone complement analysis and a kidney transplant since January 1, 2007.

Paediatric haemolytic uraemic syndrome related to Shiga toxin-producing , an overview of 10 years of surveillance in France, 2007 to 2016.

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.

Successful treatment of a associated haemolytic uraemic syndrome by eculizumab.

Haemolytic uraemic syndrome (HUS) is a rare complication of invasive infection by (SP-HUS), especially in adults. Here we report an unusual case of a 53-year-old man presenting SP-HUS with severe multivisceral involvement. After failure of supportive care and plasma exchanges, eculizumab (anti-C5 antibody) resulted in a favourable outcome.

Complement Gene Variants and Shiga Toxin-Producing -Associated Hemolytic Uremic Syndrome: Retrospective Genetic and Clinical Study.

Background And Objectives: Inherited complement hyperactivation is critical for the pathogenesis of atypical hemolytic uremic syndrome (HUS) but undetermined in postdiarrheal HUS. Our aim was to investigate complement activation and variants of complement genes, and their association with disease severity in children with Shiga toxin-associated HUS.

Design, Setting, Participants, & Measurements: Determination of complement biomarkers levels and next-generation sequencing for the six susceptibility genes for atypical HUS were performed in 108 children with a clinical diagnosis of post-diarrheal HUS (75 Shiga toxin-positive, and 33 Shiga toxin-negative) and 80 French controls.

Anticomplement Treatment in Atypical and Typical Hemolytic Uremic Syndrome.

The dissection of the pathogenic mechanisms of the various forms of the hemolytic uremic syndrome (HUS) has paved the way for the design of specific efficacious treatments. Such mechanistic approach led to a revolution in the management of atypical HUS with the use of the first-in class C5 blocker, eculizumab. The availability of this anticomplement drug has also raised unsettled questions regarding the cost or burden and optimal duration of therapy and its use in secondary HUS.

Patterns of Clinical Response to Eculizumab in Patients With C3 Glomerulopathy.

Background: Cases reports and small series of patients with C3 glomerulopathy have reported variable efficacy of eculizumab.

Study Design: Case series of C3 glomerulopathy.

Setting & Participants: Pediatric and adult patients with C3 glomerulopathy treated with eculizumab between 2010 and 2016 were identified through the C3 glomerulopathy French registry database, and a questionnaire was sent to participating French pediatric and adult nephrology centers, as well as one pediatric referral center in Québec, Canada.

Hemolytic uremic syndrome due to Shiga toxin-producing Escherichia coli infection.

The leading cause of hemolytic uremic syndrome (HUS) in children is Shiga toxin-producing Escherichia coli (STEC) infection, which has a major outbreak potential. Since the early 2010s, STEC epidemiology is characterized by a decline of the historically predominant O157 serogroup and the emergence of non-O157 STEC, especially O26 and O80 in France. STEC contamination occurs through the ingestion of contaminated food or water, person-to-person transmission, or contact with ruminants or their contaminated environment.

[Hemolytic and uremic syndrome and related thrombotic microangiopathies: Treatment and prognosis].

Major achievements in the understanding of thrombotic microangiopathies (TMA) have not only resulted in a reclassification of TMA but most of all they have culminated in the design of new treatments and have enabled clinicians to better delineate their prognosis. Recent multicenter studies have improved our understanding of the prognosis of atypical hemolytic and uremic syndromes (aHUS). More specifically, they have highlighted the role of genetic testing on predicting the recurrence of aHUS, the risk of chronic kidney disease and the recurrence following kidney transplantation.

[Hemolytic and uremic syndrome and related thrombotic microangiopathies: Epidemiology, pathophysiology and clinics].

Thrombotic microangiopathies (TMA) represent an eclectic group of conditions, which share hemolytic anemia and thrombocytopenia as a common defining basis. Remarkable breakthroughs in the physiopathological setting have allowed for a thorough recomposition of the disparate syndromes, which form the constellation of TMA. In this view, clinicians now discriminate thrombocytopenic thrombotic purpura (TTP) defined by a severe deficiency in ADAMTS13, which is rarely associated with a severe renal involvement and the hemolytic and uremic syndrome (HUS) in which renal impairment is the most prominent clinical feature.

Hemolytic Uremic Syndrome in Pregnancy and Postpartum.

Background: Pregnancy is associated with various forms of thrombotic microangiopathy, including hemolytic uremic syndrome. A previous small French study suggested that pregnancy-associated hemolytic uremic syndrome was to be included in the spectrum of atypical hemolytic uremic syndrome linked to complement alternative pathway dysregulation.

Design, Setting, Participants, & Measurements: We sought to retrospectively analyze the presentation, outcome, and frequency of complement alternative pathway gene variants in a larger international (France, United Kingdom, Italy) cohort of patients with pregnancy-associated hemolytic uremic syndrome.

[Well-being in adulthood of patients with chronic conditions in childhood: The GEDEPAC-2 questionnaire].

Background: In France, chronic diseases affect 3 million children. In children with chronic conditions, long-term somatic outcome has been well described, but little is known about the psychosocial aspects of well-being.

Methods: Our aim was to build a self-administered questionnaire of global well-being in adults who had a chronic disease since or during childhood using a multidimensional and nonspecific approach.

Haemolytic uraemic syndrome.

Haemolytic uraemic syndrome is a form of thrombotic microangiopathy affecting predominantly the kidney and characterised by a triad of thrombocytopenia, mechanical haemolytic anaemia, and acute kidney injury. The term encompasses several disorders: shiga toxin-induced and pneumococcus-induced haemolytic uraemic syndrome, haemolytic uraemic syndrome associated with complement dysregulation or mutation of diacylglycerol kinase ɛ, haemolytic uraemic syndrome related to cobalamin C defect, and haemolytic uraemic syndrome secondary to a heterogeneous group of causes (infections, drugs, cancer, and systemic diseases). In the past two decades, experimental, genetic, and clinical studies have helped to decipher the pathophysiology of these various forms of haemolytic uraemic syndrome and undoubtedly improved diagnostic approaches.

[Improving the quality of life of residents].

The socially interactive therapeutic robot Paro is presented in the form of a soft toy. It can benefit patients suffering from Alzheimer's as well as nurses.

Pathogenic Variants in Complement Genes and Risk of Atypical Hemolytic Uremic Syndrome Relapse after Eculizumab Discontinuation.

Background And Objectives: The complement inhibitor eculizumab has dramatically improved the outcome of atypical hemolytic uremic syndrome. However, the optimal duration of eculizumab treatment in atypical hemolytic uremic syndrome remains debated. We report on the French atypical hemolytic uremic syndrome working group's first 2-year experience with eculizumab discontinuation in patients with atypical hemolytic uremic syndrome.

Child-onset and adolescent-onset acquired thrombotic thrombocytopenic purpura with severe ADAMTS13 deficiency: a cohort study of the French national registry for thrombotic microangiopathy.

Background: Thrombotic thrombocytopenic purpura is a rare thrombotic microangiopathy, related to a severe ADAMTS13 deficiency (a disintegrin and metalloprotease with thromboSpondin type 1 repeats, member 13; activity <10% of normal). Childhood-onset thrombotic thrombocytopenic purpura is very rare and initially often misdiagnosed, especially when ADAMTS13 deficiency is acquired (ie, not linked to inherited mutations of the ADAMTS13 gene). We aimed to investigate initial presentation, management, and outcome of acquired thrombotic thrombocytopenic purpura in children.

Observations of a large Dent disease cohort.

Dent disease classically combines low-molecular-weight proteinuria, hypercalciuria with nephrocalcinosis, and renal failure. Nephrotic range proteinuria, normal calciuria, and hypokalemia have been rarely reported. It is unknown whether the changes in phenotype observed over time are explained by a decrease in glomerular filtration rate (GFR) or whether there is any phenotype-genotype relationship.

Mutation Update of the CLCN5 Gene Responsible for Dent Disease 1.

Dent disease is a rare X-linked tubulopathy characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis and/or nephrolithiasis, progressive renal failure, and variable manifestations of other proximal tubule dysfunctions. It often progresses over a few decades to chronic renal insufficiency, and therefore molecular characterization is important to allow appropriate genetic counseling. Two genetic subtypes have been described to date: Dent disease 1 is caused by mutations of the CLCN5 gene, coding for the chloride/proton exchanger ClC-5; and Dent disease 2 by mutations of the OCRL gene, coding for the inositol polyphosphate 5-phosphatase OCRL-1.

An international consensus approach to the management of atypical hemolytic uremic syndrome in children.

Atypical hemolytic uremic syndrome (aHUS) emerged during the last decade as a disease largely of complement dysregulation. This advance facilitated the development of novel, rational treatment options targeting terminal complement activation, e.g.

Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies.

Atypical hemolytic uremic syndrome (aHUS) is a rare, possibly life-threatening disease characterized by platelet activation, hemolysis and thrombotic microangiopathy (TMA) leading to renal and other end-organ damage. We originally conducted two phase 2 studies (26 weeks and 1 year) evaluating eculizumab, a terminal complement inhibitor, in patients with progressing TMA (trial 1) and those with long duration of aHUS and chronic kidney disease (trial 2). The current analysis assessed outcomes after 2 years (median eculizumab exposure 100 and 114 weeks, respectively).

An audit analysis of a guideline for the investigation and initial therapy of diarrhea negative (atypical) hemolytic uremic syndrome.

Background: In 2009, the European Paediatric Study Group for Haemolytic Uraemic Syndrome (HUS) published a clinical practice guideline for the investigation and initial therapy of diarrhea-negative HUS (now more widely referred to as atypical HUS, aHUS). The therapeutic component of the guideline (comprising early, high-volume plasmapheresis) was derived from anecdotal evidence and expert consensus, and the authors committed to auditing outcome.

Methods: Questionnaires were distributed to pediatric nephrologists across Europe, North America, and the Middle East, who were asked to complete one questionnaire per patient episode of aHUS between July 1, 2009 and December 31, 2010.

Anti-factor H autoantibody-associated hemolytic uremic syndrome: the earlier diagnosed and treated, the better.

Atypical hemolytic uremic syndrome (HUS) secondary to anti-factor H autoantibodies has a poor prognosis. The study by Sinha et al. of a large cohort of Indian children makes a substantial contribution to improved management of this form of HUS by showing that standardized titration of anti-factor H autoantibodies is applicable worldwide and that early treatment initiation and guidance of maintenance treatment by autoantibody titer monitoring significantly improve outcomes.

A new gel formulation of topical cysteamine for the treatment of corneal cystine crystals in cystinosis: the Cystadrops OCT-1 study.

Objective: To establish the safety and efficacy of a new gel formulation of cysteamine hydrochloride (CH) eye drops, for the treatment of corneal complications of nephropathic cystinosis.

Design: Open label dose response clinical trial.

Participants: Eight patients with infantile nephropathic cystinosis including 4 children, 3 adolescents, and 1 adult (mean age at inclusion, 12.