Podocyturia based assay as a predictive biomarker for systemic vascular diseases

Cardiovascular disease (CVD) remains the leading cause of age-related morbidities and overall mortality worldwide. One of the major challenges in reducing the incidence of CVD is the difficulty in detecting its presence before clinical symptoms manifest, such as hypertension, chronic kidney disease (CKD), or the occurrence of severe events like heart attacks and strokes. Damage to endothelial cells, which line all blood vessels internally, is identified as the initial event that triggers CVD. Currently, microalbuminuria, which is linked to systemic and kidney vascular injury, is considered a strong predictor of CVD risk. Recent research indicates that by the time urinary albumin starts increasing to any degree, advanced vascular injury has already occurred. Albuminuria may not provide an accurate reflection of endothelial injury due to the reabsorption of albumin in the proximal tubules before excretion, which poses a significant delay in predicting and preventing cardiovascular events. Podocytes, specialized epithelial cells lining the kidney’s glomerular basement membrane, are injured simultaneously with endothelial cells and shed into the urine (podocyturia), without distal reabsorption. Urinary podocyte shedding (podocyturia) due to microvascular injury, in contrast to albumin, is not modified by proximal tubule reabsorption and hence provides a more relevant and earlier predictor of CVD. Studies have shown that podocyturia precedes microalbuminuria and can therefore be a more robust predictor of CVD. At Teucer Biotech, we have developed a novel RT-PCR-based urinary biomarker assay which in preliminary studies has predicted the development of cardiovascular outcomes much earlier and with substantially greater predictive power than microalbuminuria. This innovative assay measures the levels of podocyte-specific podocin and nephrin mRNA in urine samples. Our goal is to develop a Point of Care urinary podocyte mRNA assay to replace microalbuminuria as a more effective predictor of systemic vascular damage and consequently CVD risk. Towards that, the SBIR Phase I proposal will focus on standardizing the assay and clinically validating its performance to demonstrate reliability and reproducibility. Aim 1 will concentrate on Assay standardization to determine precision, sensitivity, specificity, linearity, repeatability, reproducibility, and accuracy. Aim 2 will involve conducting a pilot clinical validation study in human volunteer subjects to evaluate the performance of the assay and measure stability and inter-intraday variability. Successful completion of the aims of Phase I will be followed by a Phase II application to establish the clinical utility of our assay by analyzing its predictive power in public- use datasets containing stored baseline and follow-up urine samples from cohorts with rigorously collected and adjudicated cardiovascular outcome data to create a clinical risk prediction model. Our preliminary findings, once validated, would result in a robust and reliable, non-invasive assay that would help with early CVD risk detection, leading to early interventions and thereby reducing the global burden of CVD. Project Number: 1R43HL177857-01 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Kamal Badr | Institution: TEUCER DIAGNOSTICS, INC., Omaha, NE | Award Amount: $306,101 | Activity Code: R43 | Study Section: Special Emphasis Panel[ZRG1 IVBH-V (11)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R43HL17785701