What’s New in aHUS Research? Jan 2023 Edition

Sometimes there are fascinating articles related to atypical HUS which people might miss, and it’s then that it’s particularly helpful to have our aHUS global action team direct our spotlight on aHUS research. Variations in how aHUS is classified continue to disrupt the information flow, with publications employing different names for this rare condition as well. The aHUS Alliance has pointed out this ‘babble of names’ for the disease which seems well on its way to becoming ‘formerly known as aHUS’. There’s more recognition of aHUS subgroups in the literature, as well as differentiating it from diseases with similar characteristics, but as knowledge increases we’ve yet to adopt and employ consistent terms.  

If you think this doesn’t impact patients directly, you’re mistaken. How can family doctors and specialist physicians keep track of scientific advancements when information about aHUS diagnosis and treatment is not only scattered across disciplines (hematology, nephrology, complement medicine, ob/gyn, immunology, andmore) but tagged with different key terms? How can new drugs come to market when aHUS patients seeking clinical trials (or the physicians who treat them) are thwarted by difficulties accessing how pharma and research teams list their efforts and findings? Consensus is needed among the varied names and classifications of this rare condition in order to allow people and groups to discover scientific advancements, and to explore investigational drugs or existing  aHUS treatment options.

We’d like to highlight here a few new additions to the research and publications page created by the aHUS Alliance Global Action team. The first group of newly released aHUS research is on the topic of Pregnancy, with another set about aHUS Triggers (to include COVID-19). We end our review with a recent publication regarding Intensive Care, which noted the importance of TMA multidisciplinary care teams. Why is keeping abreast of new aHUS research so important?

People who are genetically predisposed to aHUS may experience their first episode of disease early or quite late in life, with potential multi-organ damage from symptoms that can vary greatly in duration and severity. There is still much unknown about how certain circumstances regarding genetics and environmental factors may combine to trigger atypical HUS disease activity, such as:  infections (bacterial/viral), pregnancy, certain drugs, organ transplantation, cancer, and inflammation or chronic/autoimmune disease impact.  As research progresses, perhaps we’ll also have additional insights into ‘idiopathic’ cases, where people diagnosed with atypical HUS do not appear to have any underlying cause or genetic factors.

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 over well over 1,000 unique publications, it results in about 1500 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 1,000 publications specific to this condition 

by clicking this link: Atypical HUS Research & Publications)

Here’s a small sample of recent publications related to aHUS

aHUS & Pregnancy: 

Pishko et al.  Thrombocytopenia in pregnancy

“Hematologists need to be aware of the typical signs of preeclampsia with severe features and other hypertensive disorders of pregnancy to help distinguish these conditions, which typically resolve with delivery, from other thrombotic microangiopathies (TMAs) (eg, thrombotic thrombocytopenic purpura or complement-mediated TMA). Patients with chronic thrombocytopenic conditions, such as immune thrombocytopenia, should receive counseling on the safety and efficacy of various medications during pregnancy.”

Sarno et al.  A Life-Threatening Postpartum Atypical Hemolytic-Uremic Syndrome with Multiorgan Involvement

“Our case confirms that it is important to promptly identify a pregnancy-related thrombotic microangiopathy and that early therapy can be life-saving for the patient and can preserve renal function, avoiding dialysis.”

Yenebere et al.  Thrombotic microangiopathy in pregnancy: it’s more than just a “classic triad”

“CM-HUS (also known as atypical HUS) is a dysregulation disorder of the alternative complement pathway whereby complement protein mutations lead to an overactive complement cascade and eventual endothelial cell injury. Major complement gene mutations include factor H, factor I, membrane cofactor protein, factor B, complement component 3 (C3), and thrombomodulin. Similar complement gene mutations are seen in patients with preeclampsia and HELLP syndrome, demonstrating overlap between TMA conditions in pregnancy. CM-HUS triggers include medications, infections, or systemic illness, and pregnancy is considered a frequent trigger for CM-HUS, where 20% of cases occur prior to delivery and 80% of cases occur in the postpartum setting.” 

aHUS & Triggers

Bouwmeester et al.  COVID-19 vaccination and Atypical hemolytic uremic syndrome

“In conclusion, we identified COVID-19 vaccination as a potential trigger for aHUS onset or relapse in pediatric and adult patients who are not treated with C5 inhibition.” and 

“Of note, since the complement system is capricious, uncomplicated previous (COVID-19) vaccinations are no guarantee for future (non-)development of aHUS after vaccination. As the risk of aHUS recurrence after COVID-19 vaccination appears to be acceptable, we advise continuation of COVID-19 vaccination in aHUS patients, as this evidently reduces the risk of severe COVID-19 infection.”

Ul Abedin et al.  COVID-19 Associated Atypical Hemolytic Uremic Syndrome

“We present a case of 37-year-old male with recent COVID-19 infection who presented with epistaxis. His blood work was consistent with TMA and acute kidney injury (AKI). Hemodialysis and plasmapheresis (PLEX) were initiated for presumed thrombotic thrombocytopenic purpura (TTP) but after excluding ADAMTS-13 deficiency, eculizumab was started for possible atypical HUS. Renal biopsy and genetic testing ultimately confirmed diagnosis of atypical HUS.”

(Our Note for more on this topic:  aHUS & COVID-19: a Resource Page.  Info of specific interest to the atypical HUS community, including a March 2020 webinar on this topic)

Takigawa et al. Time to Onset of Gemcitabine-induced Thrombotic Microangiopathy in a Japanese Population: A Case Series and Large-scale Pharmacovigilance Analysis

The title of this publication touches upon not just a trigger for aHUS (gemcitabine-induced TMA), but several points of interest. Note that it features the title ‘thrombotic microangiopathy’ rather than aHUS, using the term complement-mediated TMA throughout the article. There are nation-specific research publications in the aHUS arena, and in certain countries there appear to be small subgroups of particular aHUS genetic profiles. Some case studies note drugs associated with triggering aHUS activity in people not formerly experiencing it, and other cases in the literature refer to aHUS relapse triggered by certain drugs.

The term ‘pharmacovigilance’ is exactly what its name implies: watchfulness (vigilance) regarding use of a specific drug (pharma). Prior to being approved for human use, and for a specific disease, medical drugs are evaluated for safety and effectiveness – but did you realize that pharmacovigilance is ongoing? Even after being licensed, efforts continue to gather long-term data and also to identify and evaluate adverse reactions.

The aHUS Global Community Board explores pharmacovigilance issues within clinical trial discussions. Indeed, the 2023 Rare Disease Day project of the global aHUS community includes AE reporting in the context of patient experiences. 

aHUS (cm-TMA) & Intensive Care

Albrecht et al. Thrombotic microangiopathies in surgical intensive care medicine with special consideration of atypical hemolytic uremic syndrome  (English, abstract)

Thrombotische Mikroangiopathien in der operativen Intensivmedizin unter besonderer Berücksichtigung des atypischen hämolytisch-urämischen Syndroms (original in German, Full)

Newly diagnosed aHUS patients often present with symptoms so severe and/or complex that specialists and critical care teams are faced with the difficult task of differentiating aHUS apart from medical conditions with similar characteristics. As noted in the results from our 2021 aHUS global poll, diagnosis may be delayed and patient care may require multiple specialists. (Atypical HUS may affect the function of the heart, lungs, central nervous system, GI tract, or other organs in addition to damaging kidney function)  An important concept noted in this publication: “A close interdisciplinary cooperation between critical care specialists and specialist disciplines experienced in the treatment of TMA, is essential for a prompt diagnosis and the initiation of the appropriate treatment.”

Questions about the aHUS Research & Publications page, to include suggestions for inclusion of additional aHUS studies and research articles, can be directed to the page curator E: linda@ahusallianceaction.org (Let us know of additional aHUS publications to include in our research lists.)

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