Composite metabolic indices and calcium oxalate stone formation: a multicenter comparative study of HOMA-IR, PAI, TyG, and METS-IR.

Urolithiasis has been increasingly recognized as a manifestation of systemic metabolic dysfunction rather than solely a local urinary disorder. In this multicenter cross-sectional study, we evaluated and compared the associations and discriminatory performance of four commonly used metabolic indices, homeostasis model assessment of insulin resistance (HOMA-IR), plasma atherogenic index (PAI), triglyceride-glucose (TyG) index, and metabolic score for insulin resistance (METS-IR), in relation to calcium oxalate stone formation. A total of 1206 adults (666 stone formers and 540 non-stone formers) were enrolled across seven tertiary centers, and calcium oxalate stone composition was confirmed by stone analysis. Metabolic indices were calculated using established formulas. Receiver-operating characteristic analyses and multivariable logistic regression models adjusted for age, sex, body mass index, hypertension, and diabetes mellitus were performed. HOMA-IR, PAI, and METS-IR demonstrated statistically significant but very limited discriminatory capacity, with AUC values only marginally exceeding 0.50, whereas TyG did not show significant discriminatory performance. In adjusted analyses, PAI (OR 1.72, 95%CI 1.09-2.71) and METS-IR (OR 1.05, 95%CI 1.01-1.08) were independently associated with stone formation, while HOMA-IR and TyG were not. These findings suggest that composite metabolic indices integrating lipid metabolism and adiposity may better reflect the metabolic milieu associated with calcium oxalate stone disease than glucose-centered insulin resistance markers alone. Although their standalone discriminatory performance is very limited, these indices may provide pathophysiological insights and serve as hypothesis-generating tools for future research.