Epidemiology, Clinical Presentation, and Pathophysiology of Atypical and Recurrent Hemolytic Uremic Syndrome

Abstract

Hemolytic uremic syndrome (HUS) includes a heterogeneous group of hemolytic disorders. Among the identified causes of HUS are infections, particularly infections with Shiga toxin-producing ESCHERICHIA COLI (STEC), complement disorders, and disorders interfering with the degradation of von Willebrand factor (VWF). Other causes for atypical HUS include the cobalamin metabolism; pregnancy/hemolysis, elevated liver enzymes, and low platelets syndrome (HELLP); drugs; and other disorders (e.g., systemic diseases appearing as HUS, such as systemic lupus erythematosus and rejection after transplantation). The group not related to STEC is often also called atypical HUS. Most of the occurrences of infectious HUS have only one episode. Recurrent episodes (recurrent HUS) have strong relationships to diseases of the complement system. In these two subgroups the prognosis is poor, with severe renal insufficiency, together with the need for renal replacement therapy. Severe arterial hypertension is common. Treatment options are limited. To better define this group of patients, the European Society for Pediatric Nephrology supported an initiative to develop a European HUS registry. In this registry, 167 patients were acquired; 73 were female (43.8%). The year of onset of the disease ranged from 1974 to 2005. The prevalence of atypical HUS/recurrent HUS can be calculated as 3.3 per million child population (< 18 years). Underlying disorders included factor H, factor I, MCP-1, pneumococci, and von Willebrand factor disturbances. In 33 patients at least one renal transplantation was performed (total, 55 kidneys); 18% were successful and 73% demonstrated recurrence or thrombosis. Treatment options were plasma substitution or plasmapheresis. Despite continued efforts, transplantation is not recommended at present for these patients. Living-related transplantation should be abandoned. New therapeutic strategies are urgently needed.

Shiga Toxin Activates Complement and Binds Factor H: Evidence for an Active Role of Complement in Hemolytic Uremic Syndrome

“…Beside EHEC-associated, diarrhea-positive HUS, hereditary forms of HUS, called atypical HUS (aHUS), have been reported (7). aHUS is a rare disease; it is usually recurrent and is characterized by a more severe course of disease with a poorer outcome than in the case of EHEC-induced HUS.…”

Clinical practice

“…Patients required it twice or thrice a week to achieve sufficiently high levels of factor H to maintain remission. Retrospectively plasma infusion and exchange have been found to limit residual renal insufficiency and the risk of end-stage renal failure [2,31,40].…”

“…Another (exceptional) possibility is splenectomy in patients with relapsing forms. It should be restricted to patients with frequent recurrences who require large amounts of plasma [2,30,40].…”

Comprehensive Genetic Analysis of Complement and Coagulation Genes in Atypical Hemolytic Uremic Syndrome

“…1 The prevalence of atypical HUS (aHUS) is estimated at 1 per 2 and 1 per 3.3 million children in the United States and Europe, respectively. 2,3 Until the recent availability of Eculizumab, aHUS carried significant morbidity and mortality, with 25% of patients dying of disease, 50% of patients progressing to end stage renal failure, and 40%-80% of patients experiencing disease recurrence after transplantation. 1,4 Uncontrolled activation of the alternative pathway of complement at the level of the cell surface has been closely linked to disease.…”