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Multidisciplinary Approach Uncovers Potential New Biomarker for Kidney Function

A new study has revealed a potential novel blood-based biomarker for assessing kidney health. Normally, the kidneys filter out a wide variety of molecules from the blood, preventing buildup of wastes and toxins. Currently available blood tests to assess kidney function rely on detecting higher levels of such molecules in the blood; however, it would be useful to have biomarkers of kidney health and function that are independent of the kidney’s filtration process. Researchers initially identified a candidate biomarker, a protein called testican-2, when looking for proteins that are secreted by the kidneys into the blood rather than cleared from it. Using an advanced technique called aptamer-based profiling, they quickly assessed over 1,300 proteins present in blood samples available from 22 patients with cardiovascular disease and found six proteins present at higher levels in blood exiting the kidney than that entering it, with testican-2 showing the highest relative increase. To determine whether this discovery might have clinical significance, the team applied the same advanced technique to samples available from over 3,500 participants in two large clinical study populations—one African American, the other White—this time to assess associations between blood proteins and standard measures of kidney function. Among their findings was the observation that testican-2 levels correlated directly with standard measures of kidney function in both cohorts. Moreover, when they analyzed follow up health information available from a subset of these participants, they found that having relatively higher levels of testican-2 at study entry was associated with a lower rate of decline in kidney function in both cohorts and a decreased risk of new-onset chronic kidney disease.

Given its potential as a biomarker for kidney health, the team also performed a series of molecular experiments to better characterize testican-2 and gain insight into possible function in human kidneys. These experiments revealed that human testican-2 is encoded by the gene SPOCK2 and is expressed exclusively by podocytes—highly specialized cells in the kidney that prevent loss of critical blood proteins into the urine during the filtration process. Additional experiments with laboratory-grown cells suggested that testican-2 may enhance formation of the tiny blood vessels involved in kidney filtration, but its actual function remains unknown. Together with data captured about other kidney proteins during the course of the study, these findings lay the foundation for future studies, such as targeted blood tests for testican-2 and direct studies of its association with kidney disease outcomes. Additional research could lead to new clinical tools for assessing kidney health and decline that could be a significant improvement over and/or addition to current methods.

Ngoa D, Wenc D, Gaoe Y,...Rhee EP. Circulating testican-2 is a podocyte-derived marker of kidney health. PNAS 117: 25026-25035, 2020.

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