Integrated proteomics reveals enrichment of oxidative stress and inflammatory proteins in the urine and stone matrix of calcium oxalate stone formers

Nephrolithiasis is a multifactorial disease associated with urinary and matrix proteins that become a focal point of research for diagnostic and preventative strategies. The functional relevance of these proteins in lithogenesis, along with their origins and impacts, remains a major subject of ongoing lithogenic research. Here, an integrated analysis was done on multiple proteome datasets compiled from various studies of normal urine (NU), urine from calcium oxalate stone formers (SFU), and calcium oxalate stone matrix (SM). Functional annotation and network analysis revealed the profound enrichment of proteins associated with oxidative stress and inflammation only in the stone-related samples (both "SFU but not NU" and "SM but not NU" cohorts). The oxidative stress and inflammation-related proteins were most abundant in the "SM but not NU" cohort and had higher proportions in the "SFU but not NU" cohort than the "NU only" cohort. KEGG pathway analysis corroborated such observation and highlighted the inclusion of proteins in the complement and coagulation pathways, particularly in SM. The findings of this study inform some mechanistic insights into the roles of calcium oxalate stone-related proteins and may help develop effective prevention and treatment strategies for nephrolithiasis.