Podocyturia based assay as a predictive biomarker for systemic vascular diseases

PROJECT SUMMARY
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.

Grant Number: 1R43HL177857-01
NIH Institute/Center: NIH
Principal Investigator: Kamal Badr