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Urine Test for Kawasaki Disease

Proteins found in urine may enable diagnosis of rare and elusive disorder (Dec. 20)

A set of proteins detected in urine by researchers at Boston Children’s Hospital may prove to be the first biomarkers for Kawasaki disease &emdash; an uncommon but increasingly prevalent disease that causes inflammation of blood vessels that can lead to enlarged coronary arteries and even heart attacks in some children. If validated in more patients with Kawasaki disease, the markers could make the disease easier to diagnose and give physicians an opportunity to start treatment earlier.

The discovery was reported online in EMBO Molecular Medicine. While only about two in 10,000 children in the U.S. develop Kawasaki disease annually, the disease is on the rise worldwide. No one knows what triggers the disease, and although it can occur at any age, it most often appears in children younger than 5 years.

Kawasaki disease is highly treatable — approximately 80% of children diagnosed with it require only one round of treatment — but making a diagnosis is often a significant challenge. If the disease is not detected early, it can have serious consequences: About 25% of children with untreated Kawasaki disease develop coronary artery aneurysms.

“The symptoms of Kawasaki disease, including fever, rash, and enlarged lymph nodes, mimic those found in many common viral or bacterial infections in children,” said Susan Kim, MD, MMSc. “The process of diagnosis includes considering a long list of possibilities. Especially in children with an incomplete presentation, a diagnosis of Kawasaki can be delayed or even missed.

“We'd like to have a test that we can use to proactively distinguish children with Kawasaki disease from those with other causes of fever,” she continued. “This would allow us to start treatment much earlier and greatly reduce the risks of long-term complications.”

Kim worked with proteomics experts to screen the protein content of urine from patients with Kawasaki disease using mass spectrometry and enzyme-linked immunosorbent assays. The team identified 190 proteins found only in the urine of children with Kawasaki disease. When validated in samples from 107 children with suspected Kawasaki disease (53 of whom were ultimately diagnosed with it), two of the proteins — filamin C and meprin A, which are associated with injury to cells in blood vessels and cardiac muscle as well as with inflammation — proved to be 98% accurate at distinguishing children with Kawasaki disease from ones with conditions mimicking the disease. Levels of the markers also closely tracked treatment responses and, in one patient, disease recurrence.

Other Kawasaki-associated markers detected in the study included proteins involved in immune activation, immune regulation, and pathogen recognition. Kim cautions that the markers are still research tools. She and her colleagues are working to develop a clinical-grade test.

Source: Boston Children’s Hospital; December 20, 2012.

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