[8]: 1933 Prior to availability of eculizumab (Soliris) and ravulizumab (Ultomiris), an estimated 33–40% of patients developed end-stage renal disease (ESRD) or died (despite the use of supportive care, e.g. plasmapheresis) with the first clinical bout of aHUS.
[14] Patients with aHUS often present with an abrupt onset of systemic signs and symptoms such as acute kidney failure,[1] hypertension (high blood pressure),[5] myocardial infarction (heart attack),[15] stroke,[9] lung complications,[15] pancreatitis (inflammation of the pancreas),[11] liver necrosis (death of liver cells or tissue),[5] encephalopathy (brain dysfunction),[5] seizure,[16] or coma.
[17] Failure of neurologic, cardiac, kidney, and gastrointestinal (GI) organs, as well as death, can occur unpredictably at any time, either very quickly or following prolonged symptomatic or asymptomatic disease progression.
[14] Patients who survive the presenting signs and symptoms endure a chronic thrombotic and inflammatory state, which puts many of them at lifelong elevated risk of sudden blood clotting, kidney failure, other severe complications and premature death.
Historically, the clinical diagnosis of TMA-causing diseases was grouped into a broad category that (in addition to aHUS) included thrombotic thrombocytopenic purpura (TTP) and Shiga-toxin-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS).
[19][21] However, it is now understood that although aHUS, STEC-HUS, and TTP have similar clinical presentations, they have distinct causes and specific tests can be conducted to differentiate these diseases.
In addition, there are other conditions that can cause TMA as a secondary manifestation; these entities include systemic lupus erythematosus (SLE), malignant hypertension, progressive systemic sclerosis (PSS, also known as scleroderma), pregnancy-associated HELLP (hemolysis, liver dysfunction, and low platelets) syndrome, and toxic drug reactions (e.g., to cocaine, cyclosporine, or tacrolimus).
[13][23] However, unlike aHUS, TTP is primarily an autoimmune disorder in which the presence of an inhibitory autoantibody results in severe deficiency of ADAMTS13, an enzyme that cleaves von Willebrand factor (vWF, a large protein involved in blood clotting) into smaller pieces.
Although some patients experienced improvements in red blood cell and platelet counts, plasma therapies generally did not result in full remission.
[31] In the UK, NICE issued guidance on the use of Eculizumab for treating aHUS, based on five evidence sources, including those used by the FDA[33] No randomised controlled trials were identified.
[35] Patients with aHUS who have ESRD are generally consigned to lifelong dialysis, which carries a 5-year survival rate of 34–38%,[36][37] with infections accounting for 14% of deaths.
[citation needed] Despite its history of use in patients with aHUS, kidney transplantation does not address the continued and uncontrolled complement activation that leads to progressive, systemic TMA.
Following kidney transplantation, the ongoing, uncontrolled, chronic complement activation associated with aHUS causes graft loss in 66% of children and 55% of adults, as well as continued inflammatory and TMA insult to other organs.
[40] Patients using either eculizumab or ravulizumab for the treatment of aHUS showed improvements in kidney function even avoiding dialysis and minimizing death.
Among those with the most commonly identified aHUS genetic mutation, the proportion of patients experiencing negative outcomes (e.g., need for dialysis, permanent kidney damage, death) within the first year rose to 70%.
[42] Prior to availability and usage of the treatments, quality of life was very poor for patients with aHUS; burdened with fatigue, renal complications, hypertension, neurological impairment, gastrointestinal distress, clotting at the site of venous access, and in worst cases, death.
[7] PE/PI is also reported to be associated with significant safety risks and is highly disruptive to patients' lives due to the requirements for extensive vascular access and frequent administration.