Exploring mechanisms of protein influence on calcium oxalate kidney stone formation.

Document Type

Article

Publication Date

8-1-2021

Publication Title

Urolithiasis

Keywords

JMG, Adult, Aged, Calcium Oxalate, Female, Humans, Kidney Calculi, Male, Middle Aged, Proteins

JAX Source

Urolithiasis 2021 Aug; 49(4):281-290

Volume

49

Issue

4

First Page

281

Last Page

290

ISSN

2194-7236

PMID

33587148

DOI

https://doi.org/10.1007/s00240-021-01247-5

Abstract

Calcium oxalate monohydrate (COM) crystals are the primary constituent of most kidney stones, but urine proteins in stone matrix are believed to be critical elements for stone formation from these crystals. Recent data have shown that hundreds of proteins appear in the stone matrix with no explanation for inclusion of so many proteins. We have proposed a stone formation model with protein stimulated COM aggregation based on polyanion-polycation aggregation, which is supported by finding that matrix is highly enriched in strongly anionic and strongly cationic proteins. Many other proteins may be drawn to such aggregates due to their limited solubility in water or charge effects. Finding similar protein enrichment in both polyarginine (pR) induced aggregates of urine proteins and COM stone matrix would support this hypothesis. Purified proteins (PP) were obtained from random urine samples of six healthy adults by ultradiafiltration. Protein aggregation was induced by adding pR to PP solutions at two concentrations; 0.25 and 0.5 µg pR/µg of PP. Samples of each fraction and the original PP mixture were lyophilized and analyzed by tandem mass spectrometry. Aggregates induced by pR addition to PP samples collected a protein mixture that mimicked the protein distribution observed in COM matrix, supporting our hypothesis. The apparently discordant behavior of certain abundant anionic proteins preferentially joining the pR aggregate, when they had demonstrated reduced abundance in COM stone matrix, suggests that this model was overdriven to aggregate. The reversal of aggregate preference of albumin at low pR addition supports this interpretation.

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