AACC: Personalized urine testing for salt sensitivity on near horizon

2019 08 05 17 59 6641 Aacc 2019 400

A novel urine test that identifies individuals' sensitivity to salt intake may only be a year away from use in clinical practice, according to researchers from the University of Virginia (UVA). They reported their findings on August 5 at the American Association for Clinical Chemistry (AACC) meeting in Anaheim, CA.

The test measures a patient's dopamine 1 receptor (D1R) recruitment, which directs the excretion of salt by the kidneys, and will be useful in diagnosing salt sensitivity in apparently healthy adults with normal blood pressure, according to the researchers.

Moving away from diagnosis by diet

The UVA researchers developed the test as a more convenient way to assess salt sensitivity, which is typically diagnosed through a stringent, two-week salt-restricted diet.

"Although the most reliable method to measure salt sensitivity is blood pressure responses to changes in dietary salt, low compliance with salt restricted diets reduces the effectiveness of this approach," the researchers noted in their AACC meeting abstract.

Only a small amount of daily sodium intake is needed for healthy body function. The American Heart Association suggests a limit of 1,500 mg of sodium per day; however, most people in the U.S. consume about 3,400 mg. Too much sodium can lead to high blood pressure, heart disease, and stroke.

Sensitivity to salt varies depending on an individual's genetic makeup, among other factors. About 15% of people in the U.S. are "salt sensitive," meaning they are more prone to the damaging cardiovascular effects of excess sodium. Conversely, another 11% are "inverse salt sensitive" and are at risk of developing hypertension if they don't get enough salt.

How it works

To validate their test, the UVA investigators first identified individuals who were salt sensitive versus salt resistant, based on change in blood pressure in response to sodium intake. They then studied their response to increasing levels of sodium.

From the participants' urine, the researchers isolated kidney cells known as renal proximal tubule cells (RPTCs). They exposed the RPTCs to salt and observed how much D1R the cells mobilized in response.

"Indicators that we considered were an individual's kidney physiology and the ability of the RPTCs to recruit dopamine 1 receptors from the cytoplasm to the plasma membrane upon a salt challenge," Kwabena Sarpong, PhD, who led the research, explained in an email. "RPTCs are shed into urine by the kidney and can provide a clinical picture of renal cell pathology, with the proximal tubule responsible for the reabsorption of about 70% of the filtered sodium load."

Salt-sensitive individuals had the least D1R recruitment and were therefore less able to eliminate salt. Salt-resistant individuals had moderate D1R recruitment, and inverse salt-sensitive individuals had high D1R recruitment.

The results imply that people could modify their salt intake based on their own salt-sensitivity profile. Research suggests that salt sensitivity is a continuous variable that can change over time and may be monitored, with diet adjusted accordingly.

Sarpong expects that UVA cardiologists will be able to administer this test within one year.

"Since this is translational and basic science research, we are currently performing rigorous high-quality reproducible assays to enable us to satisfy CLIA requirements for future use by cardiologists and other clinicians," he said.

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