Hemolytic Uremic Syndrome

Hemolytic Uremic Syndrome (HUS) is a serious disease that affects the kidneys and blood clotting system. It is a rare disease but is more common in children, especially younger than age 5, than in adults. Most cases of HUS occur after an infection of the digestive system by Escherichia coli (E. coli) bacterium. HUS is the most common cause of kidney failure in children.

Drawing of healthy red blood cells. The cells are round and smooth. Source: NIDDK

Drawing of broken red blood cells, as seen in the blood of people with hemolytic uremic syndrome. These misshapen cells may clog the tiny blood vessels in the kidneys. Source: NIDDK

Types

HUS usually occurs with or after a severe bout of diarrhea (usually bloody. In HUS cases without diarrhea are sometimes called atypical HUS. Atypical HUS is usually not caused by shiga toxin-producing E. coli, it has many of the same symptoms, including possible kidney failure.

HUS is related to another disease caused by a similar process within the capillaries called thrombotic thrombocytic purpura (TTP). These two conditions are often considered together, although HUS is more widely known. TTP is more often seen in older children and adults while HUS is seen in children. TTP is not associated with E. coli O157 infection.

Symptoms

In children, HUS follows diarrhea (90%) and less often an upper respiratory infection (10%) with E. coli. Infection of the digestive tract is called gastroenteritis and may cause vomiting, stomach cramps and bloody diarrhea. Most children who experience gastroenteritis recover fully in 2 or 3 days and do not develop HUS. In a few children, however, HUS develops when the bacteria lodged in the digestive system make toxins that enter the bloodstream and start to destroy red blood cells.

Symptoms of HUS may not become apparent until a week after the digestive problems. Children with HUS are often pale, tired, and irritable. Other signs include small, unexplained bruises or bleeding from the nose or mouth that may occur because the toxins also destroy the platelets, cells that normally help the blood to clot.

Frequently urine output is decreased and may also appear red. Urine formation slows because the damaged red blood cells clog the tiny blood vessels in the kidneys, making them work harder to remove wastes and extra fluid from the blood. The body's inability to rid itself of excess fluid and wastes may in turn cause high blood pressure or swelling of the face, hands, feet, or entire body. This progression to acute kidney failure occurs in about half of HUS cases.

Unusual bruising and uncontrolled bleeding are also symptoms of HUS.

Causes

The most common cause of HUS is infection by Escherichia coli serotype O157:H7. Other bacteria that can cause HUS are Shigella, Salmonella, Yersinia, and Campylobacter species. In rare cases, Streptococcus pneumoniae and Clostridium difficile can also cause HUS.The shiga and shiga-like toxins, produced by some strains of Shigella dysenteriae and E. coli O157:H7 are associated with approximately 70% of cases of HUS in children. Because of the cytotoxic activity of these toxins on vero cells, they are referred to as verotoxins.

Transmission of E. coli O157:H7 appears to be caused most often by contaminated food, such as ground beef and other cattle products that are undercooked, improperly washed produce, and unpasteurized dairy products. Food contaminated with E. coli does not look, smell, or taste bad.

Person-to-person contact, contamination of drinking water and recreational water,a nd contact with farm animals also are routes of transmission for E. coli O157.

HUS is also associated with viruses, including varicella, echovirus, and coxsackie virsues. HUS has also been associated with AIDS, cancer, and the administration of chemotherapeutic agents, for example, mitomycin C.

Diagnosis

Several Laboratory tests can help confirm HUS. They include:

• Hemolytic anemia: the red blood cell count is low and a peripheral blood smear, in which blood is examined under a microscope, will show that the red cells have been damaged and destroyed. This differentiates hemolysis (hemo=blood + lysis=destruction) from anemia caused by decreased production of blood cells in the bone marrow.

• Thrombocytopenia: a low platelet count

• Impaired kidney function or kidney failure: signs include uremia — an accumulation of urea and other wastes in the blood and finding blood and protein in the urine.

• Stool cultures: Since E. coli O157:O7 is the most common cause of HUS, a positive culture for E. coli O157 is a diagnostic signal. However, E. coli is often cleared from the stool before HUS is suspected, so a negative test does not exclude the disease. A positive test helps confirm HUS and will be reported to public health authorities to try to determine the source of the infection.

Treatment

Treatments, which consist of maintaining normal salt and water levels in the body, are aimed at easing the immediate symptoms and preventing further problems. Children may require a transfusion of red blood cells delivered intravenously that is, through an I.V. needle. Only the most severe cases require dialysis. Some children may sustain significant kidney damage that slowly develops into permanent kidney failure and will then require long-term dialysis or a kidney transplant. Some studies suggest that limiting protein in the child's diet and treating blood pressure with a medicine from a class of drugs called angiotensin-converting enzyme inhibitors, usually called ACE inhibitors, helps delay or prevent the onset of permanent kidney failure. Most children recover completely with no long-term consequences.

Chances of Developing Hemolytic Uremic Syndrome

Hemolytic uremic syndrome is most common in infants and toddlers (ages 6 months to 4 years). People who have immature or weak immune systems — such as young children and older adults — have the highest risk of developing hemolytic uremic syndrome after an E. coli infection.

Expected Outcome

The majority of children with HUS fully recovery from the illness. With treatment, it is fatal in less than 5% of cases. Chronic kidney problems and hypertension are common complications after HUS is resolved. A small number of children eventually require a kidney transplant. Unfortunately, HUS may reoccur in the new kidney.

In adults, the probability of recovery is low when HUS is associated with severe hypertension.

Research

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) conducts and supports research to help many kinds of people with kidney disease, including children. NIDDK's Division of Kidney, Urologic, and Hematologic Diseases (DKUHD) maintains the Pediatric Nephrology Program, which supports research into the causes, treatment, and prevention of kidney diseases in children. DKUHD supports several researchers working to find ways to prevent HUS from developing after the initial infection of the digestive system.

Controversy

It is controversial whether to treat early stage E. coli O157 infections with antibiotics. Some researchers have claimed that antibiotic treatment of children with E. coli O157:H7 infection increases the risk of developing HUS.^[1].

Other researchers maintain antibiotics are an important weapon against HUS, especially since E. coli is not the only cause and the evidence is not clear that antibiotic use is a risk factor.^[2]

References

1. ↑ Wong CS, Jelacic S, Habeeb RL, Watkins SL, Tarr, PI. The Risk of the Hemolytic-Uremic Syndrome after Antibiotic Treatment of Escherichia coli O157:H7 Infections. N Engl J Med 2000 342: 1930-1936. Abstract | Full Text
2. ↑ Safdar N, Said A, Gangnon R, Maki D. Risk of Hemolytic Uremic Syndrome After Antibiotic Treatment of Escherichia coli O157:H7 Enteritis: A Meta-analysis. JAMA. 2002;288(8):996-1001. Full Text

External Links

American Society of Pediatric Nephrology

National Kidney Foundation

National Institutes of Health: National Kidney and Urologic Diseases Information Clearinghouse

Dr.MDK.com: Interview with Galeano Narmer, MD Ped GI on HUS