# IDENTIFYING KEY PROTEINS IN CALCIUM OXALATE KIDNEY STONE FORMATION USING STONE MATRIX PROTEOMICS

> **NIH VA I01** · CLEMENT J. ZABLOCKI VA MEDICAL CENTER · 2021 · —

## Abstract

Kidney stones are a common and recurrent disease affecting more than 10% of Americans in their
lifetime, but the underlying pathophysiology remains incompletely understood. Since kidney stones occur
predominantly during middle age and affect more men than women, US veterans are a high risk group for this
disease. Current therapies have limited effectiveness, with only a modest reduction in stone recurrence rates,
and there has been no real advancement in preventive therapy for many years. A breakthrough in
understanding is clearly needed. Stones form as aggregates of calcium oxalate (CaOx) crystals with layers of
organic material, principally urinary proteins, between the individual crystals, and these proteins likely play a
critical role in stone formation. The role of proteins in stone formation is obscured by the large number of
urinary proteins found within stone matrix. Comparison of urine proteomes from stone forming and normal
individuals has failed to identify critical protein differences to date, but our recent Preliminary Data comparing
the relative abundances in proteins in CaOx stone matrix to their urinary abundances has highlighted 2 small
subsets of proteins that are likely to be key proteins, specifically including both highly anionic and highly
cationic proteins. Such a combination of proteins suggests a role for polyanion-polycation aggregates in
triggering stone formation, because we have previously shown that such aggregates stimulate CaOx crystal
nucleation and aggregation. Therefore, we hypothesize that the relative abundance of proteins critical to
the stone forming process will be increased in CaOx stone matrix compared to that seen in freshly
voided urine from the same patient, specifically including both highly anionic and cationic proteins.
While the proposed experiments will not elucidate the mechanism whereby these specific proteins become
enriched in CaOx stone matrix, confirming the presence of this specific protein mixture in a large number of
stones is necessary before mechanistic based studies exploring our suggested link between protein
aggregation and stone formation are relevant. The proposed work will identify and characterize key proteins in
stone formation in two Specific Aims. In Specific Aim 1, we will confirm enrichment of key proteins in stone
matrix using quantitative mass spectrometry to determine the relative abundance of proteins in stone matrix
and urine samples obtained from 40 CaOx stone forming patients. In Specific Aim 2, the relative abundances
of key proteins in urine under stable health conditions will be compared between our stone former panel and a
matching normal population to test for the expected increase in key protein abundance in stone former urine.
Immunoblot techniques will be used to circumvent problems associated with quantitative mass spectrometry
characterization of low abundance proteins. Identification of key proteins associated with CaOx stone
formation represents a new para...

## Key facts

- **NIH application ID:** 9858229
- **Project number:** 5I01CX001491-03
- **Recipient organization:** CLEMENT J. ZABLOCKI VA MEDICAL CENTER
- **Principal Investigator:** Jeffrey A Wesson
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858229

## Citation

> US National Institutes of Health, RePORTER application 9858229, IDENTIFYING KEY PROTEINS IN CALCIUM OXALATE KIDNEY STONE FORMATION USING STONE MATRIX PROTEOMICS (5I01CX001491-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9858229. Licensed CC0.

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