Proposed Role for Quantitative Podocyturia as a Clinical Marker of Systemic Endothelial Injury: Implications for Cardiovascular Disease and Longevity

Cardiovascular disease (CVD) remains the leading disability burden and cause of mortality worldwide. As emphasized by the cardiovascular-kidney-metabolic health construct, enhanced screening mechanisms are needed for the identification and prediction of subclinical endothelial injury and silent CVD. We hypothesized that urinary podocyte shedding (podocyturia), as a biomarker of ongoing glomerular endothelial injury, may be an earlier predictor of CVD than moderate albuminuria. Urinary podocin and nephrin messenger RNAs (podocyturia), as candidate biomarkers of endothelial/podocyte injury, were measured by quantitative polymerase chain reaction in type 2 diabetics with normal albumin excretion rates at baseline, at 3-4 years, and at 7 years. The development of CVD was collected as the outcome. On visit 1, podocyturia was significantly higher in individuals who subsequently developed CVD versus those who did not. We also found a significant association between podocyturia and obstructive coronary artery disease. Moreover, individuals with CVD risk factors that included male sex, metabolic syndrome, and type 2 diabetes were found to have significantly higher urinary podocin levels than individuals without these risk factors. Podocyturia may be an earlier predictor of cardiovascular events than moderate albuminuria.