Abstract: TH-PO0056
Distribution of Urinary Proteins Binding to Calcium Oxalate Crystals In Vitro and Comparison to Kidney Stone Matrix
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Basic Research
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic
Authors
- Knight, Brenna, Medical College of Wisconsin Department of Medicine, Milwaukee, Wisconsin, United States
- Wesson, Jeffrey, Medical College of Wisconsin Department of Medicine, Milwaukee, Wisconsin, United States
Background
Urinary macromolecules play a key—but poorly defined—role in kidney stone disease. Proteomics data show that hundreds of proteins with disparate biological functions are found in stone organic matrix, suggesting that general physical properties underlie their control on stone formation. Here, we probe how protein binding to calcium oxalate monohydrate (COM, the main component of most kidney stones) may influence matrix composition. Determining what proteins specifically concentrate via crystal binding or protein-protein interactions will inform molecular mechanisms that contribute to the formation of kidney stones.
Methods
24 hour urine samples of three healthy and three stone forming adults were obtained. Crystal binding was induced by adding either COM crystals or Na2Ox (sufficient for COM nucleation) to 500mL urine alloquots. Crystal were then separated and crystal-bound proteins were isolated by crystal dissolution. Proteins analyzed by quantitative mass spectrometry at the Mayo Clinic Proteomics Core Facility. Acquired data were compared to previously published proteomic studies of human urine and COM stones.
Results
Over 450 unique proteins were identified, with the 20 predominant proteins accounting for >80% of all sample spectral counts for each experiment and sample group. Bound proteins from normal urine were enriched in strrong polyanions and strong polycations; however, protein binding from stone former urine was dominated by uromodulin (or Tamm’s Horsfall protein) and strong polycations, but the protein ensemble was otherwise depleted in strong polyanions compared to normals. The abundance of each protein varied greatly between samples (patients) and many prominent COM matrix proteins were not identified in these COM binding experiments.
Conclusion
The results support the model that protein-protein binding contributes significantly to crystal-protein association and crystal aggregation whereby polyanions bind to COM and attract polycations. The wide spread of identified proteins and large variance between samples reflects that diverse compositions can be included in COM aggregates and reveals many open questions regarding protein selection criteria for the stone/ matrix phase.
Acknowledgment
Funding was provided by VA Merit Review CX001491 and NIDDK R01 DK140369. We appreciate the contribution from the VA for supplying the facilities that hosted this research project. We also appreciate the support from the Proteomics Core Facility at the Mayo Clinic for protein idenitfication.
Funding
- NIDDK Support