PODOCYTURIA mRNAs: EARLIER AND SUPERIOR PREDICTORS OF CARDIOVASCULAR OUTCOMES
Increased filtration of albumin, a result of injury to glomerular endothelial and epithelial cells (podocytes), leads to increased albumin excretion rate (AER) which defines \"moderate albuminuria\", a predictor of cardiovascular events (CVD). Since filtered albumin is modified by renal proximal tubule albumin retrieval, we hypothesized that urinary podocyte shedding (podocyturia), as a biomarker of ongoing glomerular microvascular injury, may be a more relevant and earlier predictor of CVD than moderate albuminuria.\n\nType II diabetic subjects (mean age: 46/60 men/women) with normal AER [<2.26 mg/mmole (20 g/mg) creatinine] and free of overt cardiovascular disease (CVD) were studied. AER and podocyte-specific proteins (podocin and nephrin) mRNAs were measured at baseline (Visit 1), 3-4 years later (Visit 2) and at 7 years (Visit 3). Development of CVD (acute coronary syndrome, stroke, and/or peripheral vascular disease) was collected as outcome. Seven-year Kaplan-Meier time-to-event (log rank) data were compared among baseline biomarker tercile groups (low, intermediate, high).\n\nAll three biomarkers increased significantly between visits. Visit 1AER terciles exhibited similar time to CVD (p=0.127), in contrast with step-wise and substantial increases in CVD events predicted by Visit 1 podocin and nephrin terciles. Considered as continuous factors, the covariate-adjusted hazard ratios (95% confidence intervals) [HR] were highest for podocin mRNA [HR=15.9 (6.1-41.8); p<0.001], intermediate for nephrin mRNA [HR=7.61 (3.75-15.5); p<0*001] and lowest for AER [HR=1.17 (1.01-1.36); p=0*041].\n\nCompared to moderate albuminuria, podocyturia predicts more accurately and at a significantly earlier time point the presence of silent systemic vascular injury ultimately manifesting as overt cardiovascular events.