It’s been a busy 4th quarter to round out 2024 for our aHUS Alliance Global Action team, and we’d like to share a few highlights from recent publications which have relevance to the atypical HUS community. Our ‘virtual library’ of aHUS-specific publications has grown over time to become a curated and categorized group of over 1,400 entries selected because of their high interest to patients and their families. Here are just a few recent additions…
Patients Speak Up about Life with aHUS
Atypical HUS patients and members+ of aHUS Alliance Global Action worked together with a team of clinician researchers and the USTMA Consortium to create an important long-range view how aHUS can affect all areas of life. Hematologists at the 66th annual American Society of Hematology were able to view these findings, which also appeared in ASH journal ‘Blood’ (vol 144). Our thanks and sincere appreciation to all 55 aHUS patients who participated.
*Anne K Hubben, Jenna Brown, Linda Burke+, Len Woodward+, Clare Martin, Keith R. McCrae, Shruti Chaturvedi. Patient Reported Outcomes during Long-Term Follow-up of Atypical Hemolytic Uremic Syndrome in the Era of Terminal Complement Inhibition. Blood (2024) 144 (Supplement 1): 1238. doi.org/10.1182/blood-2024-200224
aHUS Impact on Multiple Organs
Hot off the press (15 Dec 2024), this review looked at the array of evidence regarding the damage this disease can inflict on organs other than the kidneys. Providing statistics about impact to major organs, this publication adds weight to the rationale behind a multidisciplinary team approach to aHUS/TMA management.
*Doshi, K., Yusuf, A., Licht, C. et al. Extrarenal manifestations of atypical hemolytic uremic syndrome: a systematic review and meta-analysis. Pediatr Res (2024). doi.org/10.1038/s41390-024-03771-7
Treatment: To Stop or Not?
Let’s end the year by looking at knowledge and questions on the topic of ending treatment with aHUS therapeutic drugs. The questions surrounding whether/when to discontinue treatment with a complement inhibitor are something that deserves much discussion between physician and patient. We’ve added 3 recent publications to our scroll dedicated to the topic of Discontinuing Treatment / Relapse.
This December in San Diego CA the hematology community gathered for the 66th meeting of the American Society of Hematology (ASH). A speaker at previous aHUS family conferences due to her deep expertise, Dr Anuja Java published an article for the ASH Education Program titled ‘Beyond TTP: “Atypical” TMAs for the Hematologist’ on this topic:
*Anuja Java. Atypical hemolytic uremic syndrome: diagnosis, management, and discontinuation of therapy. Hematology Am Soc Hematol Educ Program. 2024 Nov 25;2024(1):200-205. doi: 10.1182/hematology.2024000543.
There was a more generalized article about factors related to stopping treatment with monoclonal antibodies therapy, coving the topic of treatment patterns and factors. This was an interesting overview of discontinuing that class of drugs (to include both eculizumab & ravulizumab) with a unique focus on patient characteristics rather than specific diseases.
*Alkaabi MMS, et al. Treatment patterns and factors associated with discontinuation of monoclonal antibodies. SAGE Open Med. 2024 Aug 19;12:20503121241271817. doi: 10.1177/20503121241271817.
You won’t want to miss checking out this November 2024 publication, which is an indepth look specific to aHUS and is available in Full Text format.
*Germeni E, Cooper J, Briggs A, Laurence J. Treatment discontinuation in adults with atypical hemolytic uremic syndrome (aHUS): a qualitative study of international experts’ perspectives with associated cost-consequence analysis. BMC Nephrol. 2024 Nov 14;25(1):411. doi: 10.1186/s12882-024-03770-0
This publication is remarkable for its creative approach to the topic, including the authors’ ‘deep dive’ interviews with 10 physicians who had expertise in treating adult aHUS patients. High risk versus low risk groups were a topic, and this publication included a decision tree model. Very easy to read, and with content that both fascinated and pointed to future pathways to explore.
Personalized Treatment for Best Outcomes?
Among our ‘virtual library’ categories is a scrolling list of aHUS publications titled ‘Treatment’ which hosts scores of titles with quite a broad range of subtopics. Included are those targeted to patient treatment in the majority of nations which still do not have access to drugs like eculizumab or ravulizumab due to drug cost and/or restrictive rare disease treatment policies. Aside from the concept that drug cost drives access and treatment options, medical staff and research teams have pondered what constitutes ‘Best Practice’ for treatment duration and dosage. No longer is it assumed that aHUS patients must all stay ‘on treatment’ with a complement inhibitor for their whole lives, but it’s clear that there still is little agreement on treatment regimens and how to manage relapse risk factors.
Individualized treatment seems the logical choice, but questions abound regarding exactly how to tailor treatment to each patient in a way that provides the best long-term health and quality of life. Patients and their families may want a closer look at the concept strongly advised by the authors, and utilizing this term: Personalised Dosing Strategy (PDS).
*Mikačić I, Marić N. Individualised therapeutic approach to the patient with atypical haemolytic-uraemic syndrome. Clin Med (Lond). 2024 Nov;24(6):100250. doi: 10.1016/j.clinme.2024.100250. Epub 2024 Oct 4. PMID: 39368665; PMCID: PMC11539228.
If you or a family member receive ravulizumab infusions, or that’s under consideration, here’s an unique opportunity to read three key articles newly available in one ‘plain language’ format. Although the NIH hosts the publication on its site HERE, be sure to click the box at the top right of the page marked ‘View on Publisher’s Site’ to find a wealth of information and images written in simple terms. There at Becaris Publishing you’ll find an overview of 3 studies, which included both children and adults with aHUS treated with ravulizumab. For aHUS patients either using that drug, or considering a switch in treatment, this Becaris version gives information about kidney function, monitoring patient treatment effectiveness, and noted any adverse effects experienced by study participants.
*Nowicki M, Printza N. Ravulizumab in adults and children with atypical hemolytic uremic syndrome: a plain language summary of three studies. J Comp Eff Res. 2024 Nov;13(11):e240103. doi: 10.57264/cer-2024-0103. Epub 2024 Oct 10.
Diagnosing aHUS: Another Look
Before a patient can receive treatment, a rapid and accurate diagnosis is required. This is a difficult task for physicians, as atypical HUS is a ‘diagnosis of exclusion’ after medical conditions with similar symptoms and clinical profiles are ruled out. Currently researchers and clinicians are looking at the different presentations of aHUS and what may cause them (etiology). In the case of aHUS and pregnancy, experts are looking at ‘pregnancy associated aHUS’ and ‘pregnancy triggered aHUS’ and contemplating the science regarding pregnancy to either mask or unmask atypical HUS. Gray area and knowledge gaps abound, as it appears that there are sub-types of aHUS rather than a single disease – although experts have yet to agree on names (nomenclature) for these variations.
Why does this matter? If we better understand the nuances of atypical aHUS as a disease, as well as finding new ways to specifically identify and quantify precisely what’s going on with each patient, medical teams will be able to target treatment with a personalized approach to crafting an individualized and optimal care plan.
Distinguishing different diseases with those with similar characteristics was a key aspect within this recent publication, as types of hemolytic uremic syndromes (HUSs) have distinct differential causes, courses, and treatments. Interestingly, terminology utilized here may be new to many readers: CaHUS (complement associated, complement mediated HUS); FHAA (complement mutation/factor H autoantibody), and notations in Table 1 ‘Noncomplement investigations of TMAs’. This publication’s list of contributing authors reads like a ‘Who’s Who’ in aHUS literature:
*Kavanagh D, Ardissino G, Brocklebank V, Bouwmeester RN, Bagga A, Ter Heine R, Johnson S, Licht C, Ma ALT, Noris M, Praga M, Rondeau E, Sinha A, Smith RJH, Sheerin NS, Trimarchi H, Wetzels JFM, Vivarelli M, Van de Kar NCAJ, Greenbaum LA. Outcomes from the International Society of Nephrology Hemolytic Uremic Syndromes International Forum. Kidney Int. 2024 Dec;106(6):1038-1050. doi: 10.1016/j.kint.2024.09.012. Epub 2024 Oct 10. PMID: 39395628.
It’s difficult to imagine the challenging, double edged sword of physicians who diagnose children with atypical HUS in a critical care setting. In a recent Chinese study analyzed the diagnosis and treatment of 105 rare disease patients in the pediatric ICU, twelve children were diagnosed with aHUS. In the abstract available, authors noted most rare disease cases were complex and called for a multi-disciplinary care approach.
*Wang P, Liu YC, Qian SY. The current diagnosis and treatment situation of rare disease in the pediatric intensive care unit. Zhonghua Er Ke Za Zhi. 2024 Oct 2;62(10):989-994. Chinese. doi: 10.3760/cma.j.cn112140-20240312-00173. PMID: 39327967.
Have there been recent publications which indicate advancements of knowledge on the ‘How’ or tools to aid aHUS diagnosis? In a word, yes – let’s look at two of special interest. A new and interesting article published in October 204 aHUS diagnosis by Rink et al which looked at ultrasound as a way to analyze renal damage to distinguish different forms of HUS.
*Rink L et al. . Ultrasound analysis of different forms of hemolytic uremic syndrome in children. Front Pediatr. 2024 Oct 23;12:1433812. doi: 10.3389/fped.2024.1433812.
Utilizing prior knowledge and experience with the modified Ham (mHam) assay, the authors developed multiple complement ‘biosensors’ as a method to both diagnose aHUS (aka CM-TMA) as well as to monitor therapeutic levels of complement blockade in patients.
*Cole et al. Complement Biosensors Identify a Classical Pathway Stimulus in Complement-Mediated Thrombotic Microangiopathy Blood (2024) 144 (24): 2528–2545. https://doi.org/10.1182/blood.2024025850
All these, and more publications,
can be found in our aHUS ‘virtual library’.
A ‘Virtual Library’ of aHUS-specific Research – What is that?
Often publications with advancements and insights into this very rare disease are scattered across medical journals related to nephrology and hematology specialties, but atypical HUS information can be found under varied terms and across specialty areas. That’s where we come in, since as aHUS patients and family caregivers ourselves we have a vested interest in staying up-to-date with current research. It’s likely that other families affected by aHUS may wish to key into a specific topic, so to aid navigation of our ‘Research and Publications’ page we’ve not only categorized entries but also have added links to jump to each Scroll (topic section) to speed your search.
Research articles about atypical HUS are listed within our website on topic-specific lists within our Info Centre, where you can see a list for “New Research” which are then also listed by category. Scroll topic categories are: New Research, Critical Care, Diagnosis, Treatment, Discontinuing Treatment/Relapse, Thrombotic Microangiopathy (TMA), Extra Renal (Effects on Organs other than Kidneys), Pregnancy, Transplants, Genetics, Complement, Secondary aHUS, Triggers, Research in Specific Nations, Case Studies, Patient Registries: Publications, Drug Discovery/Research, Summary Articles/Literature Reviews, Consensus Documents/Guidelines, and Varied Topics.
(Note: All entries from the ‘New Research’ scroll additionally are cross-listed at the start of each specific topic. While this ‘library’ has grown to over 1,400 unique publications, it results in about 1800 dual entries – such as a study that examines mutation impact on disease management, and thus listed on both Genetics and Treatment scrolls.)
Visit our ‘virtual library’ of over 1,400 publications specific to aHUS
by clicking this link: Atypical HUS Research & Publications
Keeping Pace with Advancements: Are you ‘aHUS Aware’?
The aHUS Alliance Global Action team encourages researchers to release their studies and publications in full text versions, with Open Access to facilitate sharing knowledge. Additionally, we welcome and applaud those individuals and groups who include “Plain Language Versions” as part of their publication’s Supplementary Materials.
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