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Updated: Oct 19, 2025

Estimation of Urinary Nanocrystals in Humans using Calcium Fluorophore Labeling and Nanoparticle Tracking Analysis
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Oxidative Modifications Switch Modulatory Activities of Urinary Proteins From Inhibiting to Promoting Calcium Oxalate

Sakdithep Chaiyarit1, Visith Thongboonkerd1

  • 1Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Molecular & Cellular Proteomics : MCP
|September 25, 2021
PubMed

Insights

Oxidative modifications of urinary proteins promote calcium oxalate (CaOx) stone formation by enhancing CaOx crystallization, growth, and aggregation. This study reveals a key mechanism driving the increasing global incidence of kidney stone disease.

Area of Science:

  • Nephrology
  • Biochemistry
  • Proteomics

Background:

  • Kidney stone disease incidence is rising globally, yet pathogenic mechanisms remain unclear.
  • Urinary proteins play a role in modulating calcium oxalate (CaOx) stone formation.

Purpose of the Study:

  • To investigate the effects of oxidative modifications on urinary proteins.
  • To determine how these modifications influence CaOx stone formation processes.

Main Methods:

  • Performic oxidation of urinary proteins from healthy individuals.
  • Oxyblot assay and tandem mass spectrometry (nanoLC-ESI-Q-OT-MS/MS) for protein characterization.
  • Crystal assays to evaluate CaOx crystallization, growth, and aggregation.

Main Results:

  • Oxidative modification significantly increased protein oxidation levels.
  • Mass spectrometry identified a greater number of oxidatively modified proteins in modified urine.
  • Oxidatively modified urinary proteins promoted CaOx crystallization, crystal growth, and aggregation, unlike nonmodified proteins which inhibited these processes.

Conclusions:

  • Oxidative modification of urinary proteins shifts their function from inhibition to promotion of CaOx stone formation.
  • This represents the first direct evidence linking urinary protein oxidation to increased kidney stone disease risk.
Keywords:
crystalinhibitionnephrolithiasisoxidative stresspromotionurine

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