Active clinical trials for "Hemolytic-Uremic Syndrome"

Atypical hemolytic uraemic syndrome is caused by defects in the regulating factors in the alternative pathway of the complement system. Triggering can cause an uncontrolled complement activation with endothelial damage and thrombotic micro-angiopathy, especially in the kidneys. This can result in endstage renal failure. Complement activation during hemodialysis has been described as a result of contact between blood and the dialysis membrane. Our hypothesis is that patients with atypical hemolytic uraemic syndrome have a stronger complement activation during hemodialysis than patients with another underlying kidney disease. This could be a reason to treat patients with endstage renal failure due to atypical hemolytic uraemic syndrome preferentially with peritoneal dialysis instead of hemodialysis.

The Hemolytic Uremic Syndrome (HUS) in its typical form occurs after a food born infection with a shiga-toxin secreting bacteria, usually Escherichia coli of the O157H7 serotype. An outbreak of bloody diarrhea followed by HUS begun after a collective meal with 120 persons on June 8th, 2011 in Bègles, a city of Bordeaux urban area (CUB). At least 9 patients, 8 adults and 1 child have been involved in this HUS outbreak, E. coli of the O104:H4 serotype being demonstrated in most patients. This outbreak is remarkable by its preponderance in adults and women, its aggressiveness with multiorgan involvement , i.e. the kidneys, brain, liver, pancreas, and skin. Pathophysiology, prognosis, and treatment of typical HUS are poorly defined, particularly in adults who are usually not involved in typical E. coli O157H7 HUS. The aim of the present study is to gain knowledge on these different aspects of the HUS, including response to therapy.

This protocol is intended to formally collect data on the treatment of aHUS with eculizumab in Japanese patients.

The purpose of this study is to investigate the clinical, cognitive outcome and psychosocial outcome of haemolytic uraemic syndrome in childhood. The haemolytic uraemic syndrome (HUS) is the leading cause of acute renal failure in childhood. The more common typical HUS is mostly caused by Shigatoxin-producing enterohaemorrhagic Escherichia coli (EHEC). The rarer atypical HUS is mainly caused by different genetic abnormalities in complement regulatory proteins. About 50 till 60 percent of all patients with HUS develop a severe acute renal failure and require dialysis. Resulting from new diagnostic and therapeutic approaches the survival rate increased during the last years. Despite this, there are only few data concerning long-term prognosis, cognitive and motoric development, as well as psychological coping and health-related quality of life of affected children and their parents.

To understand how AKI (Acute Kidney Injury) leads to chronic kidney disease so therapies can be found to alter the progression of events thereby significantly impacting the long-term outcomes of children who develop AKI.

Haemolytic uremic syndrome (HUS) is defined by the presence of the classic triad of non-immune microangiopathic hemolytic anemia (negative direct Coombs), thrombocytopenia and acute renal failure. Histological lesions of HUS are characterized by a systemic thrombotic microangiopathy (TMA), which mainly affects the renal vessels, with wall thickening, thrombosis and obstruction of the vascular lumen. Atypical HUS (aHUS) is a subtype of HUS in the TMA phenomena that results from the loss of regulation of the alternative complement pathway on cell surfaces and is generally considered to be from a genetic cause. Approximately 10% of HUS cases are classified as atypical HUS, which are associated with a more adverse prognosis, with a mortality rate up to 25% and progression to end stage renal disease in more than 50% of cases.

Diarrhea-associated hemolytic uremic syndrome (D+HUS) is defined as a prodrome of enteritis followed by thrombocytopenia (< 150,000/mm3), microangiopathic hemolytic anemia, and signs of variable degrees of renal damage (increase in serum Cr, proteinuria, and/or hematuria) . Our aim is to detect the most reliable early predictors of poor prognosis to identify children at major risk of bad outcome who could eventually benefit from early specific treatments.

The investigators propose to characterize MPs in aHUS and TTP both at the onset and throughout treatment. The investigators believe that the number, size, and cell origin of MPs will differ between these two diseases. The hypothesis is that endothelial derived MPs will be higher in number and comprise a larger portion of the MP population in aHUS and that platelet MPs will comprise a larger number and greater proportion of MPs in TTP. The investigators believe that MP identity and number can be used to reliably differentiate between aHUS and TTP at disease onset.

Eculizumab is a humanized monoclonal IgG antibody against protein C5 that works to inhibit the activation of the terminal complement cascade. The Eculizumab is currently FDA approved for the treatment of Paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome (aHUS) and has been shown to improve the quality of life and overall survival in these patients. aHUS is a life-threatening disease of complement mediated thrombotic microangiopathy often triggered by an inciting event, such as an infection or immunocompromised state. Pregnancy has also been identified as an inciting event, with patients most often experiencing aHUS in the postpartum period. Due to its rare nature, pregnancy-associated aHUS is often mistaken for preeclampsia or hemolysis, elevated liver enzyme, low platelet (HELLP) syndrome. As standard treatment for preeclampsia and HELLP syndrome is completion of the pregnancy by expediting delivery of the baby. A missed diagnosis of aHUS can result in delays in treatment, including use of Eculizumab when appropriate; such delay can increase the risk of maternal morbidity and mortality. When aHUS is suspected in the postpartum period, Eculizumab could be initiated early; however, there is limited data on use of Eculizumab in this setting.

A single site observational study aiming to: (i) Identify cases of previously undiagnosed thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic syndrome (aHUS) in a cohort of women with complicated pregnancies (ii) Characterise the clinical features of these cases and (ii) Identify clinical features or biomarkers which may help distinguish TTP/aHUS from other complications of pregnancy such as preeclampsia