Stone former urine proteome demonstrates a cationic shift in protein distribution compared to normal

Area of Science:

• Nephrology
• Proteomics
• Biochemistry

Background:

• Urine proteins are present in calcium oxalate stones, but their role in stone formation remains unclear.
• Decades of research have not definitively established the function of urinary proteins in the pathogenesis of kidney stones.

Purpose of the Study:

• To compare the relative abundance of abundant urine proteins in idiopathic calcium oxalate stone formers versus normal individuals.
• To identify potential differences in urine proteomes that correlate with kidney stone disease.

Main Methods:

• Collected mid-morning urine samples from 25 stone formers and 14 normal individuals.
• Isolated urine proteins using ultrafiltration.
• Characterized urine proteomes via label-free spectral counting mass spectrometry for relative protein abundance comparison.

Main Results:

• Identified 407 unique proteins, with 38 predominant proteins comprising over 82% of spectral counts.
• Found equivalent high-abundance proteins but significant differences in moderate abundance proteins (immunoglobulins, transferrin, epidermal growth factor) between cohorts.
• Observed a cationic shift in protein distribution in stone formers (22%) compared to normals (18%), potentially diminishing protein charge stabilization.

Conclusions:

• No single protein appears to solely control calcium oxalate stone formation.
• Increased immunoglobulins and transferrin in stone formers may indicate inflammatory activity, but causality is undetermined.
• The observed cationic shift in urine protein distribution could promote protein and crystal aggregation, increasing stone formation risk.