Abstract
Primary hyperparathyroidism (pHPT) is marked by mineral imbalances, often leading to nephrolithiasis and osteoporosis. While imaging remains the cornerstone for stone detection, there is growing interest in biochemical markers that could enhance diagnostic accuracy. This study investigates the calcium-to-magnesium (Ca/Mg) ratio as a novel biomarker for nephrolithiasis, comparing its utility to traditional 24-h urinary calcium excretion and exploring its broader clinical implications. In this retrospective study of 367 pHPT patients, clinical, biochemical, and bone mineral density (BMD) data were analyzed. Nephrolithiasis was diagnosed via imaging, and the diagnostic performance of the Ca/Mg ratio and urinary calcium excretion was assessed through receiver operating characteristic analysis. Multivariable regression was employed to identify predictors of kidney stones. The Ca/Mg ratio, with an optimal cutoff of 6.35, demonstrated superior specificity (78%) compared to 24-h urinary calcium excretion (44%) while maintaining comparable sensitivity (71% vs. 78%). Elevated Ca/Mg ratios strongly correlated with nephrolithiasis, independent of other demographic factors. Hypomagnesemia was linked to a higher prevalence of kidney stones, reduced BMD, and increased serum calcium and creatinine levels, emphasizing its impact on skeletal and renal health. The Ca/Mg ratio emerges as a promising, non-invasive biomarker for nephrolithiasis in pHPT, outperforming traditional urinary calcium measures. It reflects underlying mineral imbalances and offers a practical tool for risk stratification and clinical decision-making. These findings underscore the need for further research into magnesium-targeted interventions, which may transform the management of pHPT-related complications.