Circulating testican-2 is a podocyte-derived marker of kidney health
Debby Ngo, Donghai Wen, Yan Gao, Michelle J. Keyes, Erika R. Drury, Daniel H. Katz, Mark D. Benson, Sumita Sinha, Dongxiao Shen, Laurie Farrell, Bennet Peterson, David J. Friedman, Sammy Elmariah, Bessie A. Young, J. G. Smith, Qiong Yang, Ramachandran S. Vasan, Martin G. Larson, Adolfo Correa, Benjamin D. Humphreys, Thomas J. Wang, Martin R. Pollak, James G. Wilson, Robert E. Gerszten, Eugene P. Rhee
Abstract
Significance All existing blood biomarkers of kidney function such as creatinine and cystatin C undergo renal clearance and are thus inversely correlated with estimated glomerular filtrate rate (eGFR). Using a proteomic approach, we highlight the renal release of testican-2 among individuals undergoing invasive catheterization and show that higher blood testican-2 levels are associated with higher eGFR and slower rate of subsequent eGFR decline in two large racially diverse cohorts. In conjunction with microscopy and single-cell RNA sequencing of human kidney samples, these studies advance the concept that a protein released by the podocyte can provide insight into the kidney’s health and prognosis. Cell-based studies also raise the possibility that this protein has functional effects on neighboring glomerular endothelial cells.