Help Me Learn More About aHUS Diagnosis.

Caution: it often does not present with initial severe symptoms.

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More on Diagnosis

The initial onset of atypical hemolytic uremic syndrome (aHUS) will most likely appear to be flu-like, with lethargic behavior, pale color, and a loss of appetite. Hospitals may often send the patient home with a flu diagnosis due to not following the proper protocol of taking blood tests such as hemoglobin, hematocrit, white blood cell counts, and platelet counts to determine the underlying cause.

After initial blood tests, the hospital may conduct creatinine and BUN tests and may (or may not) reach an initial diagnosis of aHUS. The flu-like symptoms described above will continue to worsen when episodes are active. At this point, kidney function may begin to fail, often quite dramatically. In some cases, other organs experience problems. Quite often, seizures have been reported, along with other neurological issues. Gastrointestinal problems may occur as well.

During an extended atypical attack or episode, the telltale signs of aHUS are very obvious. Hemoglobin levels may fall to 6-7, when normal levels should be 11-13; Hematocrit levels may fall to the low 20s, when normal levels should be in the mid 30s. Creatinine and BUN levels start to rise, characteristics of failing kidney function. Blood pressure will become a nagging, recurring problem. Diarrhea and vomiting may also be present (sometimes with the initial onset, at other times later).

Specific Testing

Doctors can perform certain tests to help diagnose HUS and aHUS. Both HUS and aHUS share some signs and symptoms with another disease called thrombotic thrombocytopenic purpura (TTP), which has a different underlying cause. Doctors can measure levels of a certain protein in the blood, ADAMTS13, which may help clarify whether a patient has aHUS or TTP. The physician will need to rely on signs, symptoms, lab tests, and frequent visits to determine care and treatment for patients suspected of any of these potentially life-threatening diseases.

Medical staff having a discussion in a hospital hallway

Genetic Testing

When a patient becomes stable, his or her doctor may send blood samples for genetic testing to a specialized lab. In America, one of the first genetic testing facilities for aHUS patients was the University of Iowa. Under the direction of Dr. Richard Smith, Molecular Otolaryngology Research Laboratories (MORL) staff currently do the most comprehensive genetic testing available for this disease. One or more genetic abnormalities may be discovered through genetic testing, although about 50% of aHUS screening results come back as being of unknown cause (idiopathic). Since genetics is a rapidly changing field, we strongly suggest that you monitor aHUS advancements on a regular basis.  There are numerous locations now to get genetic testing done. With a cost of up to $2,000, check with your attending physician for the best options for you and your family.

Rendering of DNA's double-helix structure

Triggers vs. the Cause

It’s important not to confuse “triggers” of aHUS with the root cause. In normal life, many of us get colds, flu, and infections, and the body’s immune system deals with those properly. In aHUS, a person may get a cold and it triggers a full-blown aHUS episode. This occurs simply because the body’s immune system is not reacting properly to the event.

aHUS is typically diagnosed through a combination of clinical evaluation and laboratory tests. The diagnostic process may include:

  1. Clinical Evaluation: The healthcare provider will assess the patient’s medical history and symptoms, and perform a physical examination to look for signs of aHUS.
  2. Blood Tests*: These are crucial in the diagnosis of aHUS and may include:
    • Complete blood count (CBC): To check for anemia and abnormal blood cell counts.
    • Blood chemistry tests: To evaluate kidney function and electrolyte levels.
    • Coagulation tests: To assess blood clotting factors.
  3. Kidney Function Tests: Since aHUS can cause kidney damage, tests such as serum creatinine and estimated glomerular filtration rate (eGFR) may be performed to evaluate kidney function.
  4. Urinalysis: Urine tests can detect abnormalities such as protein or blood in the urine, which can indicate kidney damage.
  5. Genetic Testing: aHUS can be associated with genetic mutations that affect the complement system, which is part of the immune system. Genetic testing may be done to identify these mutations.
  6. Imaging Studies: In some cases, imaging studies like ultrasound, CT scans, or MRI may be used to assess the kidneys and other organs for signs of damage or abnormalities.
  7. Biopsy: A kidney biopsy may be performed in certain cases to examine a small sample of kidney tissue for signs of aHUS-related damage.

Diagnosing aHUS can be complex, and it’s important to work closely with a healthcare team that includes nephrologists and hematologists to determine the most appropriate diagnostic tests and treatment plan. Early diagnosis and intervention are crucial in managing aHUS and preventing further kidney damage.

Blood Tests

Lab results can be confusing to patients and family members when discussing a new diagnosis of aHUS. Ask a lot of questions! It is vitally important that you understand the basic lab panels—you are first in the “line of care” for yourself or your loved one and may often be called upon to give brief medical histories to medical personnel. Treatment options and frequency (e.g., more treatments, spacing out treatments, moving from plasma infusions to plasmapheresis, considering Soliris infusions) are choices that depend on trends seen in lab values in addition to the patient’s symptoms and ability to tolerate the chosen therapy.

Common lab tests ordered for aHUS patients

It’s important for you to know whether the specific lab test is trending up or down or has stabilized from each lab draw to the next. Keeping a log, diary, or paper copy of lab values is helpful to many aHUS patients and their families.

Every aHUS patient is different and no one can predict the disease’s course, so the most important goal is to aggressively monitor and treat patients. There are common lab tests used in diagnosing and monitoring aHUS. Understanding these lab values is crucial for patients and their families to actively participate in their care. Here’s a summary of the key lab tests mentioned and their significance:

Hemoglobin, hematocrit (’Crit)

Together, these are the “H&H”. Along with the red blood cell count, they relate to the ability of the patient’s blood to carry oxygen throughout the body. Higher lab values within the normal range are better since low numbers can indicate anemia which may result in feeling tired or fatigued. If the patient has a low red blood cell count, doctors may choose to add a medication that can promote increased red blood cell production, such as erythropoietin (aka, “epo”) or a similar time-release drug called Aranesp® (darbepoetin alfa).


Platelets are cell fragments that help in the clotting process. If a patient has a low platelet count, their skin may more easily bruise, so black and blue marks should be reported to the medical team.

White blood cells (WBCs)

These are immune system cells involved in defending the body against infection. A high white blood cell count can mean that there is an infection.

Lactate dehydrogenase (LDH)

LDH  is a chemical marker of aHUS disease activity. A high number or upward trend usually means that the aHUS episode is worsening (“ramping up”) so treatment may need to be more aggressive.


Haptoglobin is another marker of hemolysis (the rupturing of red blood cells). When red blood cells break down, they release hemoglobin into the bloodstream. The hemoglobin combines with a chemical called haptoglobin. A low level of haptoglobin in the bloodstream is another indicator of active HUS.

Creatinine Level

Creatinine level indicates kidney function and is another vital laboratory value to monitor. Low creatinine numbers indicate that toxins are effectively being eliminated from the body through the kidney’s production of urine. High creatinine levels mean that the kidneys are not functioning properly and that toxins can build up in the body to dangerous levels. In end-stage renal disease (ESRD), the kidneys stop clearing toxins through urine output, so dialysis is needed to remove fatal levels of toxins from the patient’s body. Protein in the urine is another measurement of kidney function, as poorly functioning kidneys spill out too much protein.

Blood urea nitrogen (BUN)

BUN is a measurement of kidney function. It may also be impacted by how well-hydrated a patient is and is an indicator of the kidney’s ability to keep body fluid levels normal. Lower BUN values are the desired trend.

Follow-up Lab Tests

Atypical HUS is characterized by repeated relapses, which can cause severe damage to vital organs, even though visible disease symptoms may be difficult to see at the onset of the disease. At the time of initial diagnosis, an aHUS patient will likely be hospitalized—from weeks to months—in order to closely monitor his or her condition, to consider and implement an effective treatment plan, and to assess both the variability and complexity of aHUS involvement. When the doctors feel the patient is healthy enough, they will begin to train the patient or parent/caregiver in all aspects of home care and will set a care plan that includes follow-up appointments, lab work, and treatments.

Patient Monitoring

Patient monitoring is particularly difficult because of the complexity, severity, and variability of the disease. A patient’s symptoms may also vary over time. Frequent lab tests can detect another episode before the patient experiences symptoms and can indicate the need for rapid treatment to protect kidney function during a relapse. Do not wait for distinct and pronounced symptoms, as often the only warnings will be a bit of tiredness, bruising, or perhaps vomiting. BE VERY PROACTIVE. Ask for labs to be drawn at the first hint of any health or behavioral issues. Lab tests can often show aHUS activity BEFORE symptoms occur; do not wait for a follow-up or next scheduled appointment!

Patients and their families should work closely with their healthcare team to understand the trends in these lab values over time. Treatment decisions, such as adjusting medication dosages or transitioning to different therapies like plasmapheresis or medications like eculizumab or ravulizumab, are often based on these trends, along with the patient’s symptoms and overall health. Keeping a log or diary of lab values can be a helpful tool in tracking the progress of aHUS and guiding treatment decisions. Open communication with the medical team is essential to ensure the best possible care for individuals with aHUS in order to maintain the patient’s kidney function.

  1. Flu-Like Symptoms: Initial symptoms that mimic the flu, such as lethargy, pale color, and loss of appetite, can make it challenging to distinguish aHUS from more common illnesses.
  2. Diagnostic Tests: The importance of basic blood tests, including hemoglobin, hematocrit, white blood cell counts, and platelet counts, in the early stages of diagnosis. These tests can provide valuable clues and should not be overlooked.
  3. Kidney Function: Monitoring creatinine and BUN levels is crucial for assessing kidney function. The rise in these levels can indicate kidney damage and dysfunction, which is a hallmark symptom or sign of aHUS.
  4. Other Organ Involvement: aHUS can affect not only the kidneys but also other organs. Neurological issues, including seizures, and gastrointestinal problems may occur during episodes.
  5. Hemoglobin and Hematocrit Levels: Significantly decreased hemoglobin and hematocrit levels, along with falling platelet counts, are indicative of aHUS during active episodes.
  6. Blood Pressure: Blood pressure issues, often recurring and difficult to control, can be associated with aHUS.
  7. Gastrointestinal Symptoms: Diarrhea and vomiting may accompany aHUS episodes, sometimes occurring at the initial onset or later in the course of the disease.

It’s important to emphasize that aHUS is a rare condition, and its symptoms can vary widely among individuals. Timely recognition and diagnosis are critical for initiating appropriate treatment and preventing severe complications.

Individuals experiencing these symptoms, especially if they persist or worsen, should seek immediate medical attention. Collaboration with healthcare professionals, including hematologists and nephrologists, is essential to manage aHUS effectively and provide the necessary care and treatment.