Advancements in diagnosis and disease characterization are needed in Canada to improve the clinical outcomes of adults and children with atypical hemolytic uremic syndrome (aHUS), a registry study suggests.
While strides have been made in the last several years, more work needs to be done, particularly in enabling access to genetic and biomarker testing, and ensuring results are obtained in a timely manner, according to the researchers.
“Raising awareness of aHUS, prompt diagnosis and treatment, and access to optimized treatment have the potential to improve outcomes and reduce the disease burden for affected patients and families,” they said.
aHUS is an extremely rare and diverse disease that is associated with the overactivation of the complement system, part of the immune system’s natural defense against infections. It causes abnormal blood clots to form in small blood vessels in the kidneys. The disease is difficult to diagnose and is often associated with a poor prognosis, particularly when patients develop end-stage renal disease (ESRD), a condition in which the kidneys are no longer able to function properly.
Initiated in 2012 with an 11-year recruitment mandate, the Global aHUS Registry (NCT01522183) has prospectively and retrospectively collected data from people of all ages who have been diagnosed with aHUS. Such registries are important for research in rare diseases, as they allow patients from all over the world to learn more about potential treatments and to enroll in studies, increasing the number of participants to include those who otherwise might not be involved.
Now, researchers in Canada analyzed data from Canadians enrolled in the Global aHUS Registry to investigate the specific challenges faced by that country’s patients in the diagnosis and management of aHUS.
The study was based on data from 37 Canadians with aHUS — 15 children and 22 adults — recorded between February 2014 and May 2017. Data was collected at the patients’ enrollment in the Global aHUS Registry and every six months thereafter for analysis.
The median age at which individuals started experiencing the first symptoms of aHUS was 25.9. Most patients were women (62.2%) and the vast majority (94.6%) had no family history of the disease.
Almost all patients (94.6%) reported no triggering factors, to include surgery or infection, prior to being diagnosed with aHUS.
More than three-quarters of the individuals (78.4%) had no conclusive information regarding genetic mutations or antibodies against complement factor H (CFH), a protein that is part of the complement system. And, among those who had available information, few had mutations or anti-CFH antibodies.
The analysis showed that nine patients — eight adults and one child — from the 37 registered experienced end-stage renal disease prior to the study.
The researchers discovered that children were less likely to develop ESRD than adults. In fact, the five-year ESRD-free survival rate, which evaluates the proportion of patients who remain free from end-stage renal disease over a period of 60 months, was 93% in children and only 56% in adults.
The enrolling physicians had reported kidney problems in all patients from the start, with 68.4% in the chronic phase of the disease — referring to the period of six months or longer following the initial symptoms.
Additionally, disease occurrences outside the kidneys, called extrarenal manifestations, were found more frequently during the initial phase of the disease than in the chronic phase. This was particularly true for occurrences involving the gastrointestinal tract — 61.1% in the initial phase versus 15.8% in the chronic phase — and those involving the central nervous system. For those involving the CNS , the occurrences were 38.9% in the initial phase versus 5.3% in the chronic.
Gastrointestinal manifestations were found more often among adults compared with children (70% versus 50%). In contrast, disease manifestations involving the respiratory system were observed more frequently in children than in adults (37.5% versus 10%).
“More genetic or anti-CFH antibody testing is needed to improve the diagnosis of aHUS, and the management of children and adults needs to consider several factors such as the risk of progression to ESRD is based on age (more likely in adults), and that the location of extrarenal manifestations differs in children and adults,” the researchers said.
The investigators said important strides have been made in Canada in the years since the aHUS Global Registry was launched.
“Recently, the availability of genetic and functional complement testing has substantially improved in Canada, along with the development of a Canadian Expert Consensus for the diagnosis of Canadian patients with aHUS. The publication of these guidelines will provide clinicians with practical and timely advice into how to best diagnose this ultra-rare disease,” the researchers said.
In addition, a new approach using personalized monitoring plans is being implemented in some centers across the country, using the genetic profile and monitoring of complement activity.
However, more needs to be done, the researchers said.
“At the national level, improvements are needed in the diagnosis and further characterization of aHUS (including genetic and anti-CFH antibody testing). We also need a better understanding of triggering factors of aHUS, extrarenal manifestations and risk factors for chronic kidney disease in aHUS,” they said.
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