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.