<p>Epidemiology of Atypical Hemolytic Uremic Syndrome: A Systematic Literature Review</p>

Abstract

Atypical hemolytic uremic syndrome (aHUS) is a rare but severe disorder that frequently has a genetic component and results from the overactivation of the alternative complement pathway. As research moves toward improved diagnosis and therapy of aHUS, it will be important to better understand its epidemiology. Our objective was to conduct a systematic literature review to assess the incidence and prevalence estimates of aHUS globally. A comprehensive literature search was conducted in Embase and MEDLINE. Additionally, practice guidelines, databases of national/international organizations, and regulatory agencies were searched. From 2960 publications identified via MEDLINE and Embase, 105 publications were eligible for full-text screening, and a total of eight full-text articles met eligibility criteria for inclusion. Regional epidemiologic estimates were obtained for Europe and Oceania. Country-specific data were available for France, Norway, Australia, and Italy. Four of the identified studies reported on the prevalence of aHUS, prevalence in the age group of 20 years or younger was ranging from 2.2 to 9.4 per million population, while the only study that reported prevalence in all ages showed a prevalence of 4.9 per million population. Six studies reported on the incidence of aHUS, annual incidence in the age group of 20 years or younger was ranging from 0.26 to 0.75 per million population, and for all ages, annual incidence was ranging from 0.23 to 1.9 per million population. To our knowledge, this is the first systematic review conducted to provide a comprehensive overview of global incidence and prevalence estimates of aHUS. In general, incidence estimates were similar across all the studies; however, prevalence data were found to be more variable. Study limitations were related to inconsistencies in the definitions of aHUS between studies and also a dearth of epidemiological studies assessing incidence and prevalence of aHUS outside of Europe.

A US cost-minimization model comparing ravulizumab versus eculizumab for the treatment of atypical hemolytic uremic syndrome

“…Atypical hemolytic uremic syndrome (aHUS) is a rare, systemic, and unpredictable disease that can cause severe, progressive organ damage and death in patients of all ages if left untreated [1][2][3][4]. Estimates of disease prevalence are variable, and range from 2.2-9.4 cases per million individuals among the general population aged ≥ 20 years [5]. aHUS is characterized by systemic thrombotic microangiopathy (TMA), resulting from uncontrolled activation of the complement system [3,4,6].…”

Efficacy and safety of the long-acting C5 inhibitor ravulizumab in patients with atypical hemolytic uremic syndrome triggered by pregnancy: a subgroup analysis

“…This study has limitations that must be noted. aHUS is an ultra-rare disease with an estimated prevalence of 4.9 per million and annual incidence rate between 0.23–1.9 per million [ 27 ]. As postpartum patients account for only around 4% of diagnosed cases of aHUS [ 3 ], there is not a large enough pool of complement inhibitor-naïve patients presenting postpartum to conduct a placebo-controlled trial.…”

Molecular Studies and an ex vivo Complement Assay on Endothelium Highlight the Genetic Complexity of Atypical Hemolytic Uremic Syndrome: The Case of a Pedigree With a Null CD46 Variant

“…If this allele were fully penetrant, it would have resulted in 0.012% of population developing aHUS. However, the reported prevalence of aHUS is far lower, ranging between two to ten per million population (0.0002-0.001%) (41), implying that the c.286+2T>G is not enough to develop the disease. Consistently, through the analysis of our pedigrees, we have found several unaffected carriers of the c.286+2T>G and that aHUS penetrance was lower than 30%.…”