Proteomic biomarker discovery in hematuria and renal pathologic correlates
Co-applicant(s): Andrew D. Paterson, Sarah Gagliano Taliun
Lay Abstract
Blood in the urine, also known as hematuria, is often a warning sign of kidney disease. People with hematuria are at higher risk of developing kidney failure. However, reports about how common hematuria is vary widely, ranging from less than 1% to over 30% of the population. Because it can be easily detected through routine urine tests, hematuria is an important but underused tool for identifying people at risk of kidney disease. In our earlier work, we studied hematuria using the UK Biobank, a large research resource that combines health information and genetic data from hundreds of thousands of participants. We identified strong genetic links between hematuria and specific genes. The most notable were COL4A3 and COL4A4, which are known to cause Alport syndrome, a hereditary kidney disease characterized by blood in the urine and damage to the kidney’s filtering structure (the glomerular basement membrane, or GBM). We also found an association with HLA-B, a gene previously linked to immune-related kidney diseases such as IgA nephropathy and steroid-sensitive nephrotic syndrome. These findings suggest that hematuria may be influenced by both structural changes in the kidney and immune system activity.
We believe hematuria is more than just a symptom—it can be a powerful clue to underlying disease processes and could help identify new diagnostic tests and treatments. To build on our findings, we will pursue two main goals:
• Aim 1: Study the genetics of GBM width, an important structural feature of the kidney filter, to see how genetic variation influences kidney health.
• Aim 2: Explore how proteins in the blood are related to hematuria, with the goal of identifying new non-invasive biomarkers.
These Aims will be pursued in two kidney disease specific cohorts called NEPTUNE and CureGN (n>1800) and in two population based cohorts called UK Biobank and All of Us (n>1,000,000). By combining genetic and protein-based studies, our research aims to reveal why hematuria occurs, what it tells us about kidney health, and how it might guide the development of better ways to diagnose, monitor, and treat kidney disease.
