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

Abstract

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.

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.