Calcium-Magnesium-Phosphate-Potassium Metabolic Network Dysregulation in Nephrolithiasis: Predictive Model Development and Mechanistic Insights

Abstract Objective To explore the pathophysiological interplay of calcium-magnesium-phosphate-potassium (Ca-Mg-P-K) metabolic networks in nephrolithiasis and establish an integrated risk prediction framework incorporating homeostatic biomarkers. Methods This hospital-based case-control study enrolled 611 nephrolithiasis patients and 624 gender-matched controls. Multivariable logistic regression identified core risk determinants, with model performance rigorously validated through ROC analysis, calibration curves, and decision curve analysis (DCA). A nomogram was constructed to enable dynamic risk visualization. Results The metabolic network-based model demonstrated exceptional discriminative capacity (AUC = 0.812, 95%CI: 0.789–0.836) and calibration accuracy (Brier score = 0.177, Hosmer-Lemeshow p = 0.852). Key predictors included calcium-magnesium ratio (Ca/Mg, aOR = 5.50), calcium-phosphate product (Ca×IP, aOR = 1.82), hypokalemia (aOR = 0.13), BMI ≥ 24, and hemoglobin reduction. The nomogram quantified individualized risk through synergistic scoring, with a score of 240 points identifying high-risk patients (sensitivity = 78.9%, specificity = 73.6%). Subgroup analyses revealed amplified risks in females (Ca/Mg OR = 10.01 vs 6.98) and those in the renal compensatory phase (eGFR > 90 group OR = 10.45). DCA validated the model's clinical utility, revealing net benefit superiority over traditional approaches across 0.3–0.8 risk thresholds. Conclusion This study establishes calcium-magnesium ratio (Ca/Mg) and calcium-phosphate product (Ca×IP) as key indicators of subclinical calcium dysregulation. The nomogram integrates metabolic network interactions to overcome single-marker limitations, with hypokalemia identified as a critical risk amplifier. This model enables early detection of network-level imbalance despite normal individual parameters, offering a clinically actionable tool for personalized nephrolithiasis prevention.