Disease definition
- aHUS is a rare, chronic, and progressive disease. It is characterized by the development of thrombotic microangiopathy (TMA), which leads to systemic organ failure1
- TMA comprises thrombosis, inflammation, and occlusion of microvasculature throughout the body, leading to ischemia and organ failure1
- TMA is defined by its clinical characteristics, which include1
- Decreased platelet count
- Evidence of organ impairment/damage (e.g. serum creatinine above the upper limit of normal (ULN))
- Evidence of microangiopathic hemolysis (e.g. elevated lactate dehydrogenase (LDH), decreased haptoglobin, schistocytes)
- Up to 25% of patients may die during the acute phase, despite extensive PE2
- 56% of adult patients with aHUS progress to end-stage renal failure or die within the first year after diagnosis, despite PE/PI3,a
aBased on a study assessing the disease presentation and outcome in a nationwide French study comprising 214 patients with aHUS (89 children and 125 adults) between 2000 and 2008.3
- Schmidtko J, et al. Am J Kidney Dis. 2013;61(2):289-299.
- Laurence J, et al. Clin Adv Hematol Oncol. 2016;14(11)Sup11:1-15.
- Fremeaux-Bacchi V, et al. Clin J Am Soc Nephrol. 2013;8(4):554-562.
Incidence and prevalence of the disease
- Incidence and prevalence1,2
- Very few sources of data are available regarding the incidence and prevalence of aHUS1
- Incidence: 0.11-2 cases/million (as estimated in Europe and the United States)1
- Prevalence: up to 3.3 cases/million/year (as estimated in Europe)1
- At least 50% of patients with aHUS have underlying inherited and/or acquired complement abnormality2,3
- Gender distribution is similar (slight predominance in females when the disease appears later in life)1
- Campistol JM, et al. Nefrologia. 2015;35(5):421-447.
- Goodship TH, et al. Kidney Int. 2017;91(3):539-551.
- Noris M, et al. Clin J Am Sco Nephrol. 2010;5(10):1844-1859.
Diagnosis
aRange found in published literature data is <5-10%.
TMA can be associated with various triggers, which may include but are not limited to pregnancy/postpartum, hypertensive emergency, autoimmune disease and transplant.
Laurence J, et al. Clin Adv Hematol Oncol. 2016;14(11)Sup11:1-15.
Acronyms
- ADAMTS13 — a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13
- aHUS — atypical hemolytic uremic syndrome
- eGFR — estimated glomerular filtration rate
- EHEC — enterohemorrhagic Escherichia coli
- LDH — lactate dehydrogenase
- TMA — thrombotic microangiopathy
- STEC-HUS — Shiga toxin-producing Escherichia coli - hemolytic uremic syndrome
- TTP — thrombotic thrombocytopenic purpura
What is the aHUS Registry?¹
- The global aHUS patient Registry (US National Institutes of Health ClinicalTrials.gov identifier: NCT01522183) is an observational, noninterventional, multicenter study initiated in April 2012 to prospectively capture postmarketing effectiveness and safety data on patients with aHUS; the Registry will record information on the progression of disease in all aHUS patients.
- The Registry fulfills postmarketing regulatory requirements by providing long-term follow up on patients with aHUS.
- Successful Registry implementation is contingent on contributions from both academia and Alexion.
- Academia provides access to global, longitudinal data and increased scientific knowledge to better manage patients.
- Alexion fosters relationships with patient advocacy groups and academic partners, building credibility and scientific integrity, while also providing transparency and clear guidelines for publication.
- A single, global aHUS patient Registry can maximize both physician and patient participation to best capture information on disease, safety, and efficacy data in a population with a very rare disease.
The aHUS Registry is currently being implemented in the following countries2:
Which patients can be included?²
Select Inclusion Criteria
- Male or female patients of any age, including minors, who have been diagnosed with aHUS
- Patients with or without an identified complement pathogenic variant or anti-complement factor antibody
- ADAMTS13 > 5% (if performed)
- Able to give written informed consent. Patient or patient's parent/legal guardian must be willing and able to give written informed consent and the patient (if minor) must be willing to give written informed consent [if applicable as determined by the central Institutional Review Boards/Independent Ethics Committees (IRB/IEC)]
Select Exclusion Criteria
- Hemolytic Uremic Syndrome (HUS) only due to Shiga toxin-producing Escherichia coli (STEC)
Scientific Advisory Board³
Members of the Scientific Advisory Board as of November 2023
| Name | Country | Institution |
|---|---|---|
| Franz Schaefer (Chair) | Germany | University Clinic Pediatric Nephrology, Heidelberg |
| Gema Ariceta (Co-Chair) | Spain | Hospital Valle d'Hebron, Barcelona |
| Margriet Eygenraam | Canada | Patient Advocate, aHUS Canada |
| Fadi Fakhouri | Switzerland | Centre Hospitalier Universitaire Vaudois, Lausanne |
| Véronique Frémeaux-Bacchi | France | Hôpital Européen Georges Pompidou, Paris |
| Larry Greenbaum | USA | Emory University, Atlanta |
| Nicole Isbel | Australia | Princess Alexandra Hospital, Brisbane |
| Christoph Licht | Canada | Hospital for Sick Children, University of Toronto |
| Christopher Patriquin | Canada | Toronto General Hospital, Toronto |
| Eric Rondeau | France | Retired |
| Nuria Saval | Spain | Alexion Pharmaceuticals, Inc. |
| Jeff Schmidt | USA | Patient Advocate, aHUS Alliance |
| Johan Vande Walle | Belgium | UZ Gent Dienst Nefrologie, Gent |
- The Registry is supported by Alexion Pharmaceuticals, Inc., with governance by an independent scientific advisory board (SAB) and national coordinators representing each participating country.1
- Some key responsibilities of the SAB are to1,3:
- Provide scientific advice on aHUS Registry-related matters.
- Propose, discuss, and evaluate program objectives with Alexion.
- Review and provide guidance on future amendments to the protocol, data variables to be collected, and case report refinements (all as appropriate).
- Provide ad hoc review of documents and periodic phone/email consultation.
- Advise on analyses and scientific questions of interest.
- Review and provide feedback on publication goals and logistics.
- Contribute to the development of the publication plan.
- Establish and follow protocols for the review and approval of external requests for analyses and publications from individual investigators or national coordinators.
- Advise, counsel, and guide individuals on publications that utilize aHUS Registry data and resources and/or use the aHUS Registry name.
- Review publication drafts before submission to journals or public release.
1. Licht C, et al. BMC Nephrol. 2015;16:207. doi:10.1186/s12882-015-0195-1
2. ClinicalTrials.gov Identifier: NCT01522183. Updated March 27, 2023. Accessed May 15, 2024. https://clinicaltrials.gov/ct2/show/NCT01522183
3. Data on file. Alexion Pharmaceuticals, Inc.