Atypical Hemolytic Uremic Syndrome

What is atypical hemolytic uremic syndrome (aHUS)?

Atypical hemolytic uremic syndrome (aHUS) is a condition that causes parts of your immune system to mistakenly attack the cells lining your blood vessels. This leads to small blood clots, reducing blood flow to your kidneys and other organs. AHUS is often caused by a genetic mutation.

Healthcare providers usually diagnose aHUS when you have three conditions together:

• Microangiopathic hemolytic anemia (when your blood cells are being destroyed so fast your body can’t generate enough new ones to replace them).
• Thrombocytopenia (too few platelets, a part of your blood that helps it clot).
• Acute kidney injury (a type of kidney failure that can be reversible).

These three conditions can happen in episodes that are triggered by other health conditions.

What is the difference between atypical and typical HUS?

In the past, HUS was categorized into two types:

• Typical (diarrhea-associated) hemolytic uremic syndrome. A form of E. coli causes typical HUS (also called STEC-HUS).
• Atypical hemolytic uremic syndrome (aHUS). A genetic mutation is the cause of about half of all cases of atypical hemolytic uremic syndrome. aHUS doesn’t cause diarrhea like typical hemolytic uremic syndrome. Healthcare providers also use the term complement-mediated thrombotic microangiopathy (CM–TMA) to describe aHUS.

What triggers aHUS?

Having a genetic mutation alone doesn’t usually cause atypical hemolytic uremic syndrome. More often, it’s triggered by other health conditions, including:

• Pregnancy.
• Cancer.
• Infections.

Certain medications, including some cancer chemotherapy agents, immunosuppressive medications, blood thinners, oral contraceptives (birth control pills) and anti-inflammatory medications.

What are the symptoms of atypical hemolytic uremic syndrome?

Symptoms of aHUS include:

• Fatigue.
• Pale skin (pallor).
• Nausea or vomiting.
• Peeing less.
• Blood in your pee.
• High blood pressure (hypertension).
• Shortness of breath (dyspnea).
• Swelling (edema).
• Confusion.
• Fever.

Most people only experience a few symptoms of aHUS, or symptoms come on slowly. You might feel like you’ve been sick for a while with something you just can’t shake. Neurological (brain and nerve) symptoms, like confusion, are less common.

What causes atypical hemolytic uremic syndrome?

A genetic mutation (a change in your DNA) or autoantibodies (proteins that attack your body’s cells) you develop against complement proteins cause atypical hemolytic uremic syndrome. You can inherit these changes from a biological parent or they can happen on their own (sporadic). Gene mutations can affect proteins called complement factors.

Complement factors are proteins that help immune cells identify and destroy harmful pathogens (germs, like bacteria and viruses). Similar to seasoning on your food, complement proteins coat pathogens and make them “tasty” so that other immune cells will ingest them. Genetic mutations in aHUS most commonly affect complement factors H, I, 3 and B.

For example, complement factor H protects your body’s cells so other complement factors won’t activate when they don’t need to. When complement factor H isn’t working properly (when the CFH gene is mutated), it doesn’t protect your cells as it should. When that happens:

• Your immune cells mistakenly attack and damage cells that line your blood vessels (endothelial cells).
• Platelets form a clot around the damage, which blocks blood vessels.
• Blood can’t get to your organs, damaging them and preventing them from working properly. Your kidneys are affected more often than other organs.
• The clots can also damage other blood cells as they go by, leading to hemolytic anemia.

How is aHUS diagnosed?

A provider usually diagnoses aHUS based on your symptoms and the results of tests that check your blood counts and how well your organs are working. They may also perform tests that rule out other conditions that cause similar symptoms (like STEC-HUS).

What tests are used to diagnose aHUS?

You might need the following tests and procedures:

• Blood tests, like a complete blood count (CBC) and kidney function tests.
• Genetic testing.
• Stool (poop) tests.
• Kidney biopsy.
• Imaging (like ultrasound or CT scan).

How is atypical hemolytic uremic syndrome treated?

How a healthcare provider treats aHUS depends on the underlying cause and severity. If you have a milder form of aHUS, your provider may monitor you and provide supportive care, like blood transfusions or high blood pressure medications.

If you have severe aHUS, you might need:

• Therapeutic plasma exchange.
• Rituximab or other medications used to treat autoimmune diseases.
• Dialysis.
• Kidney transplant (in severe cases).

For people who have complement mutations, providers commonly use medications such as eculizumab to treat atypical hemolytic uremic syndrome. Eculizumab blocks certain complement proteins, preventing your immune system from damaging your blood vessels.

Complications/side effects of treatment

Eculizumab can reduce the amount of protection you receive from meningococcal and pneumococcal vaccinations. If possible, your provider may encourage you to get these vaccinations before starting eculizumab.

Can aHUS be prevented?

Since it’s most often caused by genetic changes, you usually can’t prevent aHUS. If you’re at risk for severe illness, you may be able to avoid certain triggers.

What can I expect if I have aHUS?

If identified and caught early, providers can successfully treat episodes of acute kidney injury caused by aHUS. You can experience periods of remission (times where you don’t have symptoms) but you could have another life-threatening episode if something triggers aHUS again.

Previously, up to 50% of people with aHUS progressed to end-stage kidney disease (ESKD, the last stage of kidney failure). But studies suggest eculizumab treatment has significantly reduced the risk of ESRD in people with aHUS.

What is the survival rate of atypical hemolytic uremic syndrome?

Acute episodes of aHUS — involving kidney failure or other organ damage — are serious. There’s about a 15% risk of dying during an acute episode.

How do I take care of myself?

If you’ve been diagnosed with aHUS, talk to your provider about ways to avoid things that could trigger an episode. Make sure you know what signs and symptoms of severe illness to look out for.

When should I see my healthcare provider?

Talk to your healthcare provider if you’ve been feeling run-down or fatigued for a long time — like you’ve gotten something you just can’t shake. Tell them about any other symptoms you’ve been experiencing lately, like changes you’ve noticed in your bathroom habits.

When should I go to the ER?

Go to the emergency room if you’re experiencing severe symptoms, including:

• Peeing very little.
• Confusion or altered mental state.
• Severe swelling.
• Difficulty breathing.

What questions should I ask my doctor?

It may be helpful to ask your healthcare provider:

• How serious is my condition?
• What triggered this?
• Can I prevent episodes in the future?
• What signs and symptoms should I look out for?
• When should I follow up with you?

How common is aHUS?

AHUS is rare. It affects about 1 in 500,000 people. It’s slightly more common in adults than in children.

A note from Cleveland Clinic

Finding out you or your child has a genetic condition can be life-changing. AHUS can be serious, causing blood clots that lead to organ damage. But recently, the use of eculizumab has greatly improved the outlook for people with aHUS. If you’ve been diagnosed with aHUS, ask your provider about ways to avoid potential triggers and reduce your risk of severe illness. They can help you understand what tools you need to stay healthy.