Active clinical trials for "Hemolytic-Uremic Syndrome"

The goal of this National Registry is to is to collect information from patients with rare kidney diseases, so that it that can be used for research. The purpose of this research is to: Develop Clinical Guidelines for specific rare kidney diseases. These are written recommendations on how to diagnose and treat a medical condition. Audit treatments and outcomes. An audit makes checks to see if what should be done is being done and asks if it could be done better. Further the development of future treatments. Participants will be invited to participate on clinical trials and other studies. The registry has the capacity to feedback relevant information to patients and in conjunction with Patient Knows Best (Home - Patients Know Best), allows patients to provide information themselves, including their own reported quality of life and outcome measures.

Post-marketing safety data on patients treated and untreated with eculizumab or ravulizumab.

Hemolytic and uremic syndrome (HUS) is a clinic-biological syndrome related to thrombotic microangiopathy affecting predominantly the kidney. Atypical HUS (aHUS) has been historically defined as HUS occurring in the absence of infectious event. The role of complement dysregulation in aHUS pathophysiology has been largely demonstrated, since C genetic rare variants are present in 60-70% aHUS patients. In line with the frequency of C dysregulation in aHUS, Eculizumab, an anti-C5 monoclonal antibody, has dramatically improved aHUS patients prognosis. Numerous conditions have been associated with aHUS, including hypertensive emergency (HE), a syndrome of acute blood pressure flare associated with end-organ damage. In cases of HE-aHUS, whether primary aHUS is complicated by secondary HE, or primary HE leads to secondary aHUS is still debated. The investigators recently demonstrated that C genetic variants frequency was similar in patients with HE-aHUS and patients with aHUS without HE, suggesting a major role for C dysregulation in HE-aHUS. Consequently, the investigators propose to evaluate, in HE-aHUS patients, the benefit of a strategy with early Eculizumab therapy (used within its marketing authorization and its conditions of refunding by the health insurance in usual care), compared to standard of care including tight blood pressure control. The hypothesis suggests that C dysregulation may impact renal prognosis of HE-aHUS patients. The investigator's aim to demonstrate that early Eculizumab therapy improves prognosis of HE-aHUS patients. Method The HYPERSHU study is a randomized, controlled, open-labelled study including HE-aHUS patients with severe AKI and no evidence of other conditions associated with HUS (infections, autoimmunity, drugs, pregnancy). The investigators plan to include 62 patients. Patients will be randomized in 2 arms: Early Eculizumab therapy (for 3 months) added to standard of care (tight blood pressure control). Standard of care alone with tight blood pressure control. Renal function after 6 months is the primary evaluation criterium. HE is a frequently associated with aHUS, and strongly impacts patient renal prognosis. Efficient therapeutic strategies are still lacking for this condition. The HYPERSHU study will allow to evaluate the benefit of early Eculizumab therapy in patients with HE-aHUS and severe renal dysfunction.

This protocol is part of a larger project, COMPRare (COMPlement-mediated Rare kidney diseases), which has been financed on behalf of the EJP RD (European Joint Programme on Rare Diseases) program of EU and is leaded by a scientific consortium from 7 European countries. The partners (P) of the consortium are: P1. Radboudumc Amalia Children's Hospital (The Netherlands) P2. Semmelweis University (Hungary) P3. Cordeliers Research Center (France) P4. Max Delbruck Center for Molecular Medicine (Germany) P5. Istituto di Ricerche Farmacologiche Mario Negri (Italy) P6. Lund University (Sweden) P7. Lille University (France) The general aim of the project is to define new diagnostic tools for complement activation in order to improve patients stratification and follow-up, thereby affecting time and choice of treatment in patients with aHUS and C3G. Particularly, the specific objectives of the COMPRare are: To develop new standardized analytic assays thereby identifying specific complement prognostic biomarkers for early diagnosis, classification, improved monitoring and treatment of patients with aHUS and C3G; To in-depth characterize patients' complement abnormalities in blood, in patient-derived cells and in kidney biopsies; To identify strategies to classify VUS/LPV To find new pathophysiological pathways involved in aHUS and C3G for further improving disease diagnosis, monitoring and treatment. The results of these studies will form the basis of personalized treatment with existing and upcoming complement inhibitory drugs for these rare complement-mediated kidney diseases.

This project aims to identify, through RNA-Seq technology, the genetic alterations underlying undiagnosed rare diseases in pediatric and adult patients with early onset and with negative WES. Objective 1: Set up and validate techniques. Set-up and validation of the transcriptome analysis protocol in healthy subjects and in patients with known splicing alterations and/or altered RNA expression. Objective 2: Diagnostic phase. Study of splicing alterations and RNA levels in cultured fibroblasts obtained from skin biopsies of patients with rare genetic diseases and negative exome. Exploratory goals Compare the RNA expression profile obtained from skin biopsy-derived fibroblasts with the RNA expression profile from blood. The most relevant results will be validated in qRT-PCR. To analyze the transcriptional and protein profile heterogeneity in skin-derived fibroblasts in enrolled subjects. To explore the effects of genetic (from WES) and transcriptional (from RNA-seq) alterations in participants' plasma and serum. Healthy controls Five healthy subjects will be recruited from the staff of the Mario Negri Institute for Pharmacological Research. The coded samples will be used to set up the method of isolation and culture of skin fibroblasts and RNA-Seq. Validation group For the set-up and validation of the skin fibroblast isolation and RNA-Seq procedure, ten adult patients with known diagnosis and with alterations in RNA levels and/or splicing will be recruited as positive controls. Patients who meet the requirements described above will be contacted by the doctors of the Daccò Center for an interview explaining the project. Those who agree to participate in the study will be asked to sign the informed consent before proceeding with the experimental part. "Discovery/Exploration" group The exploration cohort will be composed of 30 symptomatic undiagnosed patients with suspected genetic disease (children and adults with infantile onset) belonging to the Clinical Center of the Mario Negri Institute for Pharmacological Research and for whom WES investigations did not reveal causative genetic alterations.

Thrombotic microangiopathies (TMAs) are a diverse, rare but serious group of diseases. Progress has been made regarding the epidemiology of TMA (Bayer CJASN 2019). It has been shown that secondary TMAs account for 95% of cases, whereas primary TMAs (atypical hemolytic syndromes (HUS) and thrombotic thrombocytopenic purpura (TTP)) account for only about 5%. However, in many cases, the pathophysiology, optimal management and prognosis of TMA remains unclear and it has been shown that patients with TMA may have renal-limited TMA or renal and hematological TMA (ie. With (mechanical anemia, thrombocytopenia, elevated LDH, decreased haptoglobin, schistocytes). In most studies, kidney biopsies are not performed and the diagnostic workup is uncomplete. As this is a rare disease, only a multicenter approach (>20 centers) over a long period of time (>10 years), with adequate diagnostic workup including kidney biopsies can help us to answer these questions (investigators in the present are usually members of the CNR-MAT (a network of the TMA centers in France).

CoRDS, or the Coordination of Rare Diseases at Sanford, is based at Sanford Research in Sioux Falls, South Dakota. It provides researchers with a centralized, international patient registry for all rare diseases. This program allows patients and researchers to connect as easily as possible to help advance treatments and cures for rare diseases. The CoRDS team works with patient advocacy groups, individuals and researchers to help in the advancement of research in over 7,000 rare diseases. The registry is free for patients to enroll and researchers to access. Visit sanfordresearch.org/CoRDS to enroll.

Thrombotic microangiopathy (TMA) is a severe and life-threatening condition, often affecting the kidneys and brain. It can occur on the background of various clinical conditions. Dysregulation of the alternative pathway of complement may be the etiological factor and this type of TMA is classified, according to the current nomenclature, as primary atypical hemolytic uremic syndrome (HUS). Half the patients with primary atypical HUS present with rare variants in complement genes, although coexisting conditions are often needed for the TMA to become manifest. In patients with secondary atypical HUS, certain coexisting conditions appear to drive the disease and treatment should target the underlying condition to remit the TMA. Recently, the investigators demonstrated, by using a novel in-house developed functional endothelial cell-based test, that complement dysregulation and overactivation is the dominant cause of disease and its sequelae in a subset of patients with secondary atypical HUS, having impact on treatment and prognosis. The investigators did first prove this concept in patients presenting with TMA and hypertensive emergency. A prospective study is needed to further corroborate these findings along the spectrum of TMA. The investigators hypothesize that their functional endothelial cell-based test, the so-called "HMEC" test, can better categorizes the TMA into different groups with potential therapeutic and prognostic implications. Thus, paving the road to the ultimate goal of precision medicine.

OBJECTIVES: I. Determine the effect of SYNSORB Pk therapy on mortality and frequency of severe extrarenal complications observed in children with acute stage E. coli-associated hemolytic uremic syndrome. II. Determine the effect of SYNSORB Pk therapy on the need for the duration of dialysis in these patients. III. Determine the effect of SYNSORB Pk therapy on the recovery of renal function and resolution of urinary abnormalities in these patients.

This study evaluates the effect of CCX168, a C5aR Antagonist, Oral Administration on Ex Vivo Thrombus Formation and Disease Activity in ten patients with diagnosis of Atypical Hemolytic Uremic Syndrome with or without genetic abnormalities in the complement system or thrombomodulin, on stable chronic extracorporeal or peritoneal dialysis therapy since at least 6 months.