What symptoms can I have?

aHUS symptoms are generally sudden, although about 20% of patients can have progressive development with milder symptoms over weeks and months. [1] The severity of the symptoms depends on the extent of small blood vessel injury and the resulting damage to the various organs in the body. [2] Symptoms that someone with aHUS may experience can include [1-5]:

Fatigue and drowsiness

Fatigue and drowsiness

Feeling sick

Feeling sick

Pale skin

Pale skin

High blood pressure

High blood pressure

Stomach pain

Stomach pain

Irritability

Irritability

Vision problems

Vision problems

Swelling

Swelling

Nausea or vomiting

Nausea or vomiting

Diarrhea

Diarrhea

Blood in the urine

Blood in the urine

Bruising

Bruising

Confusion

Confusion

While aHUS primarily damages the kidneys, it is ultimately a disease that affects the whole body. [1,2] Some patients may have complications in other organs. [1,2]

  • About 10-48% of aHUS patients have complications in the brain and nervous system, including visual abnormalities, confusion, facial paralysis, seizures, stroke, memory loss, and coma. [1-3]
  • Approximately 30% of patients with aHUS are affected by gastrointestinal problems like diarrhea, nausea, vomiting, and abdominal pain. [1,4]
  • Complications in the lungs including bleeding and low oxygen levels are observed in about 20% of aHUS patients. [2,6]
  • Approximately 10% of patients suffer from cardiovascular conditions like heart attack, heart failure, and blockages of the arteries. [2]
  • A rash in which small spots of blood appear under the skin due to leaking blood vessels can appear on the skin of aHUS patients. [7]

What is involved in aHUS diagnosis and what kinds of tests are used?

There are currently no specific tests available for aHUS. [8] A stepwise approach must therefore be taken.

The first step is a broad diagnosis of TMA (thrombotic microangiopathy), which is a group of disorders identified by [7]:

  • Hemolytic anemia: A condition in which there are fewer red blood cells in the body than normal.
  • Thrombocytopenia: A condition in which the number of platelets (small blood cells that help the blood to clot) is lower than normal.
  • Organ injury


The most common TMAs are [2]:

  • aHUS
  • STEC-HUS (Shiga toxin associated HUS)
  • TTP (thrombotic thrombocytopenic purpura)
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TMA is diagnosed with blood and urine tests, requiring confirmation of hemolytic anemia, thrombocytopenia, and one or more of the following: symptoms in the brain, damage to the kidneys, and gastrointestinal issues. [2]

The most common signs of kidney damage are [2]:

  • High levels of protein in the urine
  • Blood in the urine
  • High blood pressure
  • High levels of body waste products (such as urea and creatinine) in the blood
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A kidney biopsy, in which a small sample of your kidneys is removed with a needle and analyzed under a microscope, may be required when the kidneys are no longer able to function on their own. [1]

Once a diagnosis of TMA is confirmed, aHUS has to be distinguished from STEC-HUS and TTP, which can be challenging as these conditions have similar symptoms but come from different causes. [2,7]

To differentiate between aHUS and STEC-HUS, your doctor will ask about your history of diarrhea and bloody stools, which can point to STEC-HUS. [2]

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STEC-HUS diagnosis is confirmed by testing a stool or rectal swab for Shiga toxin-producing Escherichia coli (STEC). [7] The presence of this bacteria can be determined by analyzing the sample for bacterial DNA or for the toxin itself. [7]

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A blood test may also be used to look for signs of STEC-HUS. [2,7] Your doctor will also distinguish between aHUS and
TTP. [2]

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TTP can be diagnosed with a blood test to look for activity of a protein in your blood called ADAMTS13. [1,7] Low activity of ADAMTS13 confirms diagnosis of TTP. [2] Your doctor may also look at symptoms in your organs to differentiate between aHUS and TTP. [7]

If the test results for STEC-HUS and TTP are both negative, then the diagnosis of aHUS is considered and likely. [2] Genetic testing and complement testing may be used to confirm this diagnosis. [7]

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Since mutations in genes of the complement system are known to play a role in some aHUS patients, genetic testing, in which your DNA is analyzed to look for mutations, can provide confirmation of the diagnosis and insights for long-term treatment plans. [2,7]

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Complement testing, in which the levels of the complement proteins in your blood are measured, may also be used to confirm the aHUS diagnosis. [7] These tests, however, may not always be reliable and are complicated by the fact that complement levels can be normal in many aHUS patients and can also be affected in other diseases. [8]

Steps for aHUS diagnosis*

Steps-for-aHUS-diagnosis

*this algorithm is a simplified version of aHUS diagnosis for educational purposes only

References

  1. Campistol JM, Arias M, Ariceta G, et al. An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document. Nefrologia. 2015;35(5):421-447.
  2. Raina R, Krishnappa V, Blaha T, et al. Atypical Hemolytic-Uremic Syndrome: An Update on Pathophysiology, Diagnosis, and Treatment. Ther Apher Dial. 2019;23(1):4-21.
  3. Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis. 2011;6:60.
  4. Goodship THJ, Cook HT, Fakhouri F, et al. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference. Kidney Int. 2017;91(3):539-551.
  5. Greenbaum LA, Licht C, Nikolaou V, et al. Functional Assessment of Fatigue and Other Patient-Reported Outcomes in Patients Enrolled in the Global aHUS Registry. Kidney Int Rep. 2020;5(8):1161-1171.
  6. Schaefer F, Ardissino G, Ariceta G, et al. Clinical and genetic predictors of atypical hemolytic uremic syndrome phenotype and outcome. Kidney Int. 2018;94(2):408-418.
  7. Azoulay E, Knoebl P, Garnacho-Montero J, et al. Expert Statements on the Standard of Care in Critically Ill Adult Patients With Atypical Hemolytic Uremic Syndrome. Chest. 2017;152(2):424-434.
  8. Afshar-Kharghan V. COMPLEMENTing the diagnosis of aHUS. Blood. 2014;124(11):1699-1700.