Urinary peptidomics for neurogenic bladder risk stratification in patients with spina bifida

About This Grant

Abstract The central question in the urologic management of patients with spina bifida is how to best identify the subset of patients whose bladder dysfunction places their upper urinary tract at risk of developing chronic kidney disease. The current “gold standard” for assessment and risk stratification of lower urinary tract physiology is the videourodynamic study (VUDS) which has some limitations. Our preliminary pilot data suggests that a select urine peptide profile will be able to identify those hostile bladders which increase the risk of CKD progression. Our two specific aims leverage three established resources at the Children's Hospital of Philadelphia: i) a proteomics core lab with experience in urinary peptidomics, ii) an established urine biobank linked to known curated VUDS outcomes stored in a database (800 samples from ages range from 2 months to 45 years), and iii) an established machine learning algorithm to assign risk classes to VUDS data stored in our digital data repository. In specific aim 1 we will measure an array of peptides in urine samples from patients with known VUDS outcomes serving as ground truth to optimize and refine a panel of peptides to discriminate high or low urodynamic risk in a larger population. The panel will then be validated in an independent set of test samples. In specific aim 2, we will measure the predictive power of the urinary peptidome by comparing the starting low risk peptidomes of two cohorts of patients; those whose VUDS remained low risk and those whose VUDS progressed to high risk. Aim 2 tests our hypotheses that urinary peptide markers can serve as predictors of future urodynamic deterioration. The overarching goal of this project is to identify a panel of urinary peptides that serve to discriminate the high risk urodynamic patterns that place these patients at risk of impending upper tract deterioration. This would change clinical practice by allowing patients to collect a urine sample in an office setting (or preferably at home to send in by overnight courier) for peptidomic analysis and risk stratification leading to a more efficient use of clinical resources.