Circulating testican-2 is a podocyte-derived marker of kidney health.

Ngo D, Wen D, Gao Y, Keyes MJ, Drury ER, Katz DH, Benson MD, Sinha S, Shen D, Farrell LA, Peterson BD, Friedman DJ, Elmariah S, Young BA, Smith JG, Yang Q, Vasan RS, Larson MG, Correa A, Humphreys BD, Wang TJ, Pollak MR, Wilson JG, Gerszten RE, Rhee EP. Circulating testican-2 is a podocyte-derived marker of kidney health. Proceedings of the National Academy of Sciences of the United States of America. 2020 Oct 6; 117(40):25026-25035.

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Abstract:

In addition to their fundamental role in clearance, the kidneys release select molecules into the circulation, but whether any of these anabolic functions provides insight on kidney health is unknown. Using aptamer-based proteomics, we characterized arterial (A)-to-renal venous (V) gradients for > 1,300 proteins in 22 individuals who underwent invasive sampling. Although most of the proteins that changed significantly decreased from A to V, consistent with renal clearance, several were found to increase, the most significant of which was testican-2. To assess the clinical implications of these physiologic findings, we examined proteomic data in the Jackson Heart Study (JHS), an African-American cohort ( = 1,928), with replication in the Framingham Heart Study (FHS), a White cohort ( = 1,621). In both populations, testican-2 had a strong, positive correlation with estimated glomerular filtration rate (eGFR). In addition, higher baseline testican-2 levels were associated with a lower rate of eGFR decline in models adjusted for age, gender, hypertension, type 2 diabetes, body mass index, baseline eGFR, and albuminuria. Glomerular expression of testican-2 in human kidneys was demonstrated by immunohistochemistry, immunofluorescence, and electron microscopy, while single-cell RNA sequencing of human kidneys showed expression of the cognate gene, , exclusively in podocytes. In vitro, testican-2 increased glomerular endothelial tube formation and motility, raising the possibility that its secretion has a functional role within the glomerulus. Taken together, our findings identify testican-2 as a podocyte-derived biomarker of kidney health and prognosis.