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01-08-2021 | Original Paper

Exploring mechanisms of protein influence on calcium oxalate kidney stone formation

Authors: Garrett K. Berger, Jessica Eisenhauer, Andrew Vallejos, Brian Hoffmann, Jeffrey A. Wesson

Published in: Urolithiasis | Issue 4/2021

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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Title: Exploring mechanisms of protein influence on calcium oxalate kidney stone formation
Authors: Garrett K. Berger
Jessica Eisenhauer
Andrew Vallejos
Brian Hoffmann
Jeffrey A. Wesson
Publication date: 01-08-2021
Publisher: Springer Berlin Heidelberg
Published in: Urolithiasis / Issue 4/2021
Print ISSN: 2194-7228
Electronic ISSN: 2194-7236
DOI: https://doi.org/10.1007/s00240-021-01247-5

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Springer Medicine

Exploring mechanisms of protein influence on calcium oxalate kidney stone formation

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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