For many, kidney diseases are often associated with lifestyle choices—too much salt, too little water or perhaps a family history of diabetes. But for those diagnosed with Atypical Hemolytic Uremic Syndrome (aHUS), the reality is far more complex.
This ultra-rare and life-threatening condition can strike unexpectedly, causing blood clots, organ failure and lasting health complications.
With World Rare Disease Day 2025 highlighting the theme "More than you can imagine; an anthology of rare experiences," experts are turning their focus to aHUS, a disease that affects only 4.9 in a million people each year.
Despite its rarity, the challenges in diagnosing and treating aHUS are immense, making awareness and early intervention critical.
In a recent episode of Sinar Daily’s Life and Style Podcast, two prominent nephrologists—Professor Lim Soo Kun, a consultant nephrologist at University Malaya Medical Centre and President of the Malaysian Society of Nephrology (MSN) and Professor Dr Hermann Haller, a consultant nephrologist at Hannover Medical University and President of the US Desert Island Biological Research—discussed the complexities of kidney rare disease.
They also addressed why the disease often goes undetected and what changes are needed to improve patient outcomes.
A DISEASE THAT MIMICS MANY
One of the biggest challenges with aHUS is that its symptoms—such as severe fatigue, unexplained bruising and kidney dysfunction—can resemble other conditions.
Lim explained that aHUS is a rare but serious condition that affects multiple organs, primarily the blood and kidneys and in some cases, other organs as well.
“It occurs when the immune system mistakenly attacks small blood vessels, leading to the formation of clots that block blood flow, particularly to the kidneys, resulting in organ damage.
“If left untreated, ongoing inflammation can worsen the injury, making early intervention crucial,” he emphasised.
This overlap with conditions such as typical hemolytic uremic syndrome (HUS), which is linked to E. coli infections and thrombotic thrombocytopenic purpura (TTP), a clotting disorder, often leads to misdiagnosis.
"Diagnosing aHUS can be challenging, as its symptoms closely resemble other conditions. Infections, sepsis and autoimmune disorders like lupus can present with overlapping symptoms.
“This complexity often leads to delays in diagnosis, as clinicians must conduct thorough investigations to rule out other conditions before confirming aHUS,” he said.
Dr Haller echoed these sentiments, emphasising that even in developed countries, rare diseases often go unrecognised.
"While the kidneys and brain are most commonly affected, aHUS can also involve the cardiovascular system, lungs and even the eyes. Diagnosing aHUS requires an experienced doctor who carefully evaluates the patient from the first consultation.
"Even in Germany, where we have many nephrologists, rare diseases like aHUS require specialised training to be recognised, which is often the first challenge in diagnosis,” he mentioned.
THE URGENCY OF EARLY DETECTION
Given that aHUS can lead to life-threatening complications within days, early detection is key. Yet in Malaysia, diagnosing the disease presents unique challenges. Lim pointed out three major hurdles:
"First, as Dr Haller mentioned, it is rare, meaning nephrologists may not encounter it frequently, which can sometimes lead to delayed diagnosis. Second, there are limitations in local diagnostic capacity.
“A crucial step in diagnosing aHUS is distinguishing it from TTP, which requires the ADAMTS13 test. Currently, this test is only available at a single lab in Ampang Hospital and due to batching requirements, results take two to three weeks.
“Lastly, access to treatment remains a challenge. Since the condition is uncommon, essential medications may not always be readily available in hospitals. Clinicians often need to submit applications to procure these drugs, which can further delay treatment,” he said.
Dr Haller expanded on the urgency of timely intervention, explaining how aHUS rapidly affects kidney function.
He explained that kidney damage can occur rapidly, often leading to acute kidney failure at an early stage.
“Without timely intervention, this can progress to chronic kidney failure, forcing patients into dialysis. This poses not only a serious health burden for the patient but also a significant financial strain on healthcare systems, as long-term dialysis is costly," he said.
GENETIC AND ENVIRONMENTAL TRIGGERS
Unlike lifestyle-related kidney diseases, aHUS is primarily driven by genetics and environmental triggers.
"As Dr Haller mentioned, many cases of aHUS may be linked to genetic disorders. However, it is important to emphasise that a genetic test is not required for the initial diagnosis.
"Instead, diagnosis is primarily based on clinical evaluation and laboratory tests. Genetic testing becomes significant later for guiding treatment decisions, determining the need for long-term therapy and assessing family risk,” Lim mentioned.
Dr Haller explained that understanding the disease requires a twofold approach: recognising the condition itself and grasping its underlying pathophysiology, due to its genetic nature.
He stressed that as a doctor, it is crucial to grasp how the disease progresses, particularly the interaction between two key mechanisms.
“First, there is the molecular defect, as it is a genetic disease where the immune system, specifically the complement system, is impacted by a genetic mutation. Secondly, there is vascular injury or dysfunction, which plays a significant role. Triggers such as pregnancy, infections and even certain medications can set off the condition.
"One key trigger is pregnancy, as it creates an immunological interaction between the mother and baby, causing the complement system to become highly activated. During pregnancy, the immune system operates at an accelerated pace and any underlying defects can become apparent.
“aHUS is a rare but serious complication of pregnancy that must be recognised. While uncommon, it is essential to diagnose aHUS at the first signs, as early treatment can save both the mother and the baby,” he highlighted.
Lim added that infections—including COVID-19—have been identified as potential triggers.
"For individuals with a genetic predisposition, the condition may manifest with or without an external trigger, even in mild cases," he said.
THE FUTURE OF TREATMENT IN MALAYSIA
Despite advancements in treatment, Malaysia still lags in managing aHUS effectively. Lim spotlighted that in Malaysia, there is no comprehensive registry to track the prevalence of aHUS over the years or determine whether cases are increasing.
“Even at my hospital, we see only two to three cases a year, though some may go underdiagnosed, especially if patients are referred to a hematologist based on their symptoms,” he said.
Meanwhile, Dr Haller highlighted Germany’s progress on aHUS.
“Over the past 15 years, greater awareness of aHUS has revealed the complexity of its symptoms, often leading patients to consult either a neurologist or hematologist first, depending on their primary presentation.
“Establishing specialised aHUS centres has shown that the condition is more prevalent than previously believed,” he shared.
When it comes to solutions, Lim emphasised the need for specialised training and faster diagnostics.
"Education and specialised training are crucial for local nephrologists to enhance their ability to make timely diagnoses and provide prompt treatment. One essential diagnostic test, the ADAMTS13 test, currently has a turnaround time of two to three weeks.
“We are actively exploring ways to shorten this period to ensure faster and more efficient diagnoses,” he added.
As for treatment, both experts agreed that access to medication remains vital.
"The encouraging news is that we now have an antibody capable of treating both the acute and chronic phases when needed, marking a significant breakthrough.
“With this advancement, we can not only provide a complementary diagnosis but also intervene promptly to preserve both the organ and the patient,” Dr Haller said.
HOPE FOR A RARE DISEASE
While aHUS remains an uncommon and underdiagnosed condition, awareness and medical advancements offer hope.
As Malaysia works towards improving its diagnostic and treatment capabilities, early detection and intervention remain key to ensuring that those affected by this silent yet severe disease receive the care they need.
As Lim put it, "The goal is to prevent organ damage and ultimately reduce the risk of kidney failure, ensuring that patients can avoid the need for dialysis."