B-279 Differentiation of urinary biomarkers in idiopathic calcium oxalate stone disease

Abstract

Acidic matrix macromolecules, widely distributed across mineralized tissues, are believed to play a critical role in regulating crystal formation. The present study investigates key urinary biomarkers in both patients with idiopathic renal calcium stones and healthy controls, focusing on their influence on crystal nucleation and growth. Among the principal families of acidic macromolecules detected in urine, glycosaminoglycans (GAGs) and hyaluronan (HA) appear to modulate crystal formation from calcium and oxalate ions within the renal tubular environment. Our analysis of urinary GAGs isolated from stone-formers and controls revealed that HA is consistently present in the urine of stone-formers and is excreted at significantly higher levels (12% of total GAGs in stone-formers compared to 6% in controls). We propose that the presence of resident stones induces local inflammation and facilitates the extravasation of plasma components, thereby creating a microenvironment conducive to the formation of serum-derived hyaluronan-associated protein (SHAP–HA). This complex is implicated in HA-mediated cell and crystal adhesion, stabilization of the extracellular matrix (ECM), and the promotion of crystal nucleation and growth. To conduct this investigation, urine samples were collected from both stone-formers (pre- and post-stone removal) and healthy controls. Urinary macromolecules were recovered not only from the urine samples themselves but also from crystals formed within the urinary milieu. A total of 158 samples were analyzed. The demographic profile of participants included an age range of 32–63 years, with a male-to-female ratio of 58:42. The mean urinary pH across all samples was 6.33 ± 0.23, although group-specific differences in mean pH were observed. Urinalysis was performed for all specimens to confirm sample integrity. Urinary glycosaminoglycans (GAGs) were subsequently isolated, and the predominant species identified were chondroitin sulfate A/C (CS), dermatan sulfate (DS), heparan sulfate (HS), and hyaluronan (HA). The hexuronate content of urinary GAGs followed the order: post-treated stone-formers < active stone-formers << healthy controls. Active stone-formers exhibited enhanced urinary excretion of HA, whereas no increase in urinary HA was observed in the post-treated group. Nevertheless, both active and post-treated stone-formers demonstrated a higher proportion of HA relative to total GAGs when compared with healthy controls. Importantly, both stone-former groups exhibited reduced total urinary GAG content but an increased relative proportion of HA. These findings suggest that urinary GAGs, and particularly HA, may function as protective or risk-modifying factors in the pathogenesis of renal stone disease. Elevated urinary hyaluronan content may serve as a valuable biomarker in both active and post-treated stone-formers, enabling the monitoring of calcium oxalate (CaOx) biomineral formation in vivo.