Discover hemolytic uremic syndrome (HUS) - its causes, symptoms, diagnosis, and treatment options on Meri Sehat - your ultimate health guide for rare but serious kidney conditions.

Hemolytic Uremic Syndrome

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Syed Intisar Hussain

Overview

Hemolytic uremic syndrome (HUS) is a rare but serious medical condition characterized by the destruction of red blood cells, kidney damage, and low platelet count. 
&nbsp;

Hemolytic uremic syndrome (HUS) was first described in 1955 by Swiss pediatric hematologist Conrad von Gasser and his colleagues. In 1983, researchers identified a toxin produced by some strains of E. coli that was lethal to kidney cells and named it Shiga toxin (Stx). There are two types of Shiga toxin, with type 2 being strongly associated with HUS. 
&nbsp;

Initially, researchers believed hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) to be the same condition. However, the discovery of a protein called ADAMTS13 helped establish them as two different diseases<a href="#accordion">[1]</a>. 
&nbsp;

Hemolytic uremic syndrome (HUS), is a condition that combines both scientific complexity and clinical urgency. It is a rare and life-threatening disorder that affects the kidneys, blood cells, and sometimes the brain. The disease is characterized by the breakdown of red blood cells, the formation of blood clots, and damage to the small blood vessels in the body. In the pediatric population, HUS is one of the leading causes of acute renal injury. 
&nbsp;

In the United States, hemolytic uremic syndrome occurs at a rate of 0.5-2.1 cases per 100,000 population per year, with a higher incidence in children under 5 years of age<a href="#accordion">[1]</a>. A total of 274 cases of HUS were reported in the US in 2015, with 122 cases occurring in children aged 1-4 years<a href="#accordion">[1]</a>. Non-Stx HUS is less common than STx-HUS, accounting for 5-10% of all cases. HUS rates in children under 15 years of age in other countries range from 0.91 to 1.44 cases per 100,000 population<a href="#accordion">[1]</a>. 
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There seems to be some seasonal variation in HUS cases, with a peak in cases in summer and fall. However, there are no gender differences, as both sexes are affected equally. 
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The hemolytic uremic syndrome is typically divided into two main types<a href="#accordion">[2][3]</a>: 
&nbsp;

Shiga Toxin Hemolytic Uremic Syndrome (Stx-HUS): This is the more common type of HUS, accounting for over 90% of cases. It is caused by certain strains of E. coli bacteria that produce toxins known as Shiga toxins. Stx-HUS most commonly affects children under the age of five and can lead to serious complications such as kidney failure. It is also regarded as diarrhea-positive HUS. 
&nbsp;

Atypical Hemolytic Uremic Syndrome (aHUS): It is a rare form of HUS and only accounts for 5-10% of cases<a href="#accordion">[1]</a>. The genetic condition is more common in adults and results from gene mutations of the complement regulatory proteins. Also known as diarrhea-negative HUS, infections or environmental factors can also trigger atypical HUS. Moreover, streptococcus pneumoniae is responsible for 40% of all causes of atypical hemolytic uremic syndrome<a href="#accordion">[1]</a>. The disease can lead to severe and life-threatening complications, such as kidney failure and stroke. 
&nbsp;

The definition of atypical HUS excludes cases of secondary HUS, which occur as a symptom of another underlying condition, such as malignancy, <a href="https://merisehat.pk/disease/hiv-61">HIV </a>infection, organ transplants, bone marrow transplants, autoimmune disorders, and the use of certain drugs or medications. 
&nbsp;

Signs and Symptoms

Hemolytic uremic syndrome is associated with a medical triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury<a href="#accordion">[4]</a>&nbsp;.

The symptoms of hemolytic uremic syndrome (HUS) can vary depending on the cause. The most common cause is infection with certain strains of E. coli bacteria. The initial symptoms of HUS caused by E. coli may include<a href="#accordion">[5]</a>.

<ul>
	<li>Diarrhea (which is often bloody)</li>
	<li>Abdominal pain</li>
	<li>Cramping or bloating</li>
	<li>Vomiting</li>
	<li>Fever 
	&nbsp;</li>
</ul>

As HUS progresses, it can damage the blood vessels and cause red blood cell destruction, which can lead to anemia and blood clots in the kidneys. Some of the common symptoms of these changes include:

<ul>
	<li>Pale skin</li>
	<li>Extreme fatigue</li>
	<li>Shortness of breath</li>
	<li>Easy bruising or unexplained bruises</li>
	<li>Unusual bleeding</li>
	<li>Decreased urination or blood in the urine</li>
	<li>Swelling of the legs, feet or ankles (and sometimes the face, hands or entire body)</li>
	<li>Confusion</li>
	<li>Seizures</li>
	<li>Stroke</li>
	<li>High blood pressure. 
	&nbsp;</li>
</ul>

Note: The symptoms of HUS can resemble other conditions. If you experience any of the above symptoms, contact a healthcare professional immediately.

Causes

Hemolytic uremic syndrome (HUS) is most commonly caused by certain strains of Escherichia coli (E. coli) bacteria, particularly in children under 5 years of age. E. coli is a group of bacteria found in the intestines of healthy humans and animals. However, some strains can cause diarrhea. 
&nbsp;

Consumption of undercooked meat, unpasteurized milk, and unwashed fruits and vegetables is a major source of E. coli exposure. Furthermore, E. coli can also spread through an oral-fecal route. Therefore, not washing hands after using the bathroom or changing a baby&rsquo;s diaper can cause the bacteria to transfer from the hands to the mouth when one eats. 
&nbsp;

Some strains of E. coli that cause diarrhea also produce Shiga toxin. The toxin enters the bloodstream and results in microthrombi. As platelets are used up, thrombocytopenia sets in. Furthermore, damage to the blood vessels results in the breakdown of red blood cells, causing hemolytic anemia. The damaged red blood cells and platelets can then clog the glomeruli in the kidney. Thus, interfering with the kidney&rsquo;s functioning and leading to acute kidney injury. 
&nbsp;

However, most people infected with E. coli do not develop HUS.

Other causes of HUS include other infections, certain medications used to treat cancer or suppress the immune system, pregnancy, and certain health conditions. 
&nbsp;

A rare genetic form of HUS, known as atypical HUS, can be passed down to children, and the mutated gene may be activated by triggers like infections, medications, or chronic health conditions. 
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Diagnosis

There are no screening tests for hemolytic uremic syndrome.

Diagnosis is based on a physical exam, a review of medical history, and a variety of tests. The doctor will examine the patient to look for signs and symptoms of the condition, including checking for abnormal bruising or bleeding, high blood pressure, or swelling. Medical tests that may be used to diagnose hemolytic uremic syndrome include: 
&nbsp;

<ul>
	<li>Blood Tests - To check for anemia and low platelet count. Blood urea nitrogen (BUN), serum creatinine, and serum electrolyte levels are also measured to assess for acute kidney injury.</li>
	<li>Urine Tests - To check for the presence of blood or protein in the urine</li>
	<li>Stool Sample Tests - To identify the presence of harmful bacteria such as E. coli or Shigella.</li>
	<li>Imaging Tests - Scans such as ultrasound to check the kidneys or other organs for damage or abnormalities. It can also help rule out obstruction.</li>
	<li>Complement Serology Testing - Low levels of complement factor B and CH50 often point to a diagnosis of atypical HUS. 
	&nbsp;</li>
</ul>

In some cases, a kidney biopsy may be performed to confirm the diagnosis and assess the severity of kidney damage. It&#39;s important to receive a proper diagnosis and prompt treatment for HUS, as the condition can progress quickly and lead to serious complications. 
&nbsp;

Treatment

Hemolytic uremic syndrome (HUS) requires hospital treatment as the kidneys are not functioning properly and lost fluids and electrolytes need to be carefully replaced. 
&nbsp;

<h5>Medical Interventions:</h5>

It may include IV transfusions of red blood cells or platelets to help reverse the symptoms of <a href="https://merisehat.pk/disease/anemia">anemia </a>and promote normal blood clotting.

If the patient has lasting kidney damage, their doctor may recommend medications to lower blood pressure and prevent or delay further kidney damage.

For atypical HUS caused by a genetic mutation, eculizumab may be prescribed to prevent additional damage to blood vessels. Eculizumab and ravulizumab are two FDA approved monoclonal antibodies for the treatment of atypical HUS. However, vaccination to prevent <a href="https://merisehat.pk/disease/bacterial-meningitis">meningitis </a>is required beforehand. 
&nbsp;

<h5>Surgery And Other Procedures:</h5>

This may also be recommended based on the patient&#39;s symptoms, underlying cause of HUS, and any complications. 
&nbsp;

<ul>
	<li>Kidney Dialysis - It may be necessary to filter excess fluid and waste from the blood, with long-term dialysis required for significant kidney damage. 
	&nbsp;</li>
	<li>Plasma Exchange - The patient&#39;s plasma is replaced with fresh or frozen donor plasma. 
	&nbsp;</li>
	<li>Kidney Transplant - A kidney transplant may be necessary in cases of severe kidney damage. It is considered safe for children suffering from end-stage renal disease (ESRD). 
	&nbsp;</li>
</ul>

Hemolytic Uremic Syndrome (HUS) may lead to a number of complications. Some of the potential complications of HUS may include: 
&nbsp;

<ul>
	<li>Kidney Failure: This is one of the most common complications of HUS. The disease damages the small blood vessels in the kidneys, leading to a decreased ability to filter waste from the blood. In severe cases, kidney failure can occur, which may require dialysis or a kidney transplant. 
	&nbsp;</li>
	<li>Neurological Complications: HUS can damage the blood vessels in the brain, leading to a number of neurological complications, such as stroke, coma, and seizures. 
	&nbsp;</li>
	<li>Anemia And Bleeding: HUS can cause anemia, which is a decrease in red blood cells. This can lead to symptoms, such as fatigue, weakness, and shortness of breath. In addition, HUS can interfere with the body&#39;s ability to form blood clots, leading to a higher risk of bleeding. 
	&nbsp;</li>
	<li>High Blood Pressure: HUS can cause high blood pressure, which can lead to further damage to the blood vessels in the kidneys and other organs. 
	&nbsp;</li>
	<li>Heart Complications: In rare cases, HUS can cause damage to the heart, leading to heart failure or other heart-related complications. 
	&nbsp;</li>
</ul>

Hemolytic-uremic syndrome (HUS) is primarily caused by certain strains of E. coli bacteria. Exposure to E. coli can occur through various means, including:

<ul>
	<li>Consuming contaminated meat or produce</li>
	<li>Swimming in pools or lakes contaminated with feces</li>
	<li>Having close contact with an infected person, such as within a family or at a child care center. 
	&nbsp;</li>
</ul>

The following groups are at the highest risk of HUS:

<ul>
	<li>Children aged 5 or younger</li>
	<li>Adults aged 65 or older</li>
	<li>Individuals with weakened immune systems</li>
	<li>Those with specific genetic variations that increase susceptibility to HUS. 
	&nbsp;</li>
</ul>

It is possible for meat or products contaminated with E. coli to not show any visible signs of contamination, making it important to take preventative measures against E. coli infection and other foodborne illnesses. The following measures can help prevent hemolytic uremic syndrome: 
&nbsp;

<ul>
	<li>Avoid consuming unpasteurized milk, juice, and cider, as they may be a source of E. coli contamination.</li>
	<li>Practice good hygiene by washing hands thoroughly before eating and after using the restroom or changing diapers.</li>
	<li>Clean utensils and food surfaces frequently to reduce the risk of cross-contamination.</li>
	<li>Ensure that meat is cooked to an internal temperature of at least 160 degrees Fahrenheit to kill any potential E. coli bacteria.</li>
	<li>When defrosting meat, use a microwave or refrigerator to thaw it rather than leaving it at room temperature.</li>
	<li>Keep raw foods separate from ready-to-eat foods to prevent contamination. Avoid placing cooked meat on plates that have been in contact with raw meat.</li>
	<li>Store the meat below in the refrigerator to minimize the risk of fluids from raw meat dripping onto the produce.</li>
	<li>Avoid swimming in potentially contaminated water. Moreover, refrain from swimming if suffering from diarrhea. 
	&nbsp;</li>
</ul>

Key Points

<ul>
	<li>Hemolytic uremic syndrome (HUS) was first described in 1955 by Swiss pediatric hematologist Conrad von Gasser and colleagues. In 1983, researchers identified a toxin produced by some strains of E. coli that was lethal to kidney cells and named it Shiga toxin (Stx).</li>
	<li>Researchers initially thought that hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) were the same conditions, but later the discovery of a protein called ADAMTS13 helped to differentiate the two conditions.</li>
	<li>Hemolytic Uremic syndrome is a rare and life-threatening disorder that affects the kidneys, blood cells, and sometimes the brain.</li>
	<li>The hemolytic uremic syndrome is associated with a medical triad consisting of three signs. These signs include microangiopathic hemolytic anemia, which is damage to the red blood cells, thrombocytopenia, which is a decrease in the number of platelets in the blood, and acute kidney injury.</li>
	<li>The symptoms of hemolytic uremic syndrome (HUS) can vary depending on the cause. The most common cause is infection with certain strains of E. coli bacteria.</li>
	<li>Treatment involves IV transfusions of red blood cells or platelets to help reverse the symptoms of anemia and promote normal blood clotting.</li>
	<li>Eculizumab and ravulizumab are two FDA approved monoclonal antibodies for the treatment of atypical HUS. 
	&nbsp;</li>
</ul>

[1] Malvinder S Parmar MBBS. Hemolytic-uremic syndrome. Practice Essentials, Background, Pathophysiology.

[2] Atypical hemolytic uremic syndrome. National Organization for Rare Disorders.

[3] Hemolytic Uremic syndrome . UpToDate

[4] Hemolytic uremic syndrome: Causes, symptoms & treatment. Cleveland Clinic.

[5] Hemolytic uremic syndrome (HUS). Mayo Clinic

[6] Hemolytic uremic syndrome: Causes, symptoms, treatment, and more. WebMD.

[7] Liu Y, Tian S, Thaker H, Dong M. Shiga Toxins: An Update on Host Factors and Biomedical Applications. Toxins (Basel). 2021;13(3):222. Published 2021 Mar 18. doi:10.3390/toxins13030222