Altered Calcium and Vitamin D Homeostasis in First-Time Calcium Kidney Stone-Formers

BACKGROUND: Elevated serum 1,25-dihydroxyvitamin D (1,25(OH)(2)D) concentrations have been reported among cohorts of recurrent calcium (Ca) kidney stone-formers and implicated in the pathogenesis of hypercalciuria. Variations in Ca and vitamin D metabolism, and excretion of urinary solutes among first-time male and female Ca stone-formers in the community, however, have not been defined. METHODS: In a 4-year community-based study we measured serum Ca, phosphorus (P), 25-hydroxyvitamin D (25(OH)D), 1,25(OH)(2)D, 24,25-dihydroxyvitamin D (24,25(OH)(2)D), parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF-23) concentrations in first-time Ca stone-formers and age- and gender frequency-matched controls. RESULTS: Serum Ca and 1,25(OH)(2)D were increased in Ca stone-formers compared to controls (P = 0.01 and P = 0.001). Stone-formers had a lower serum 24,25(OH)(2)D/25(OH)D ratio compared to controls (P = 0.008). Serum PTH and FGF-23 concentrations were similar in the groups. Urine Ca excretion was similar in the two groups (P = 0.82). In controls, positive associations between serum 25(OH)D and 24,25(OH)(2)D, FGF-23 and fractional phosphate excretion, and negative associations between serum Ca and PTH, and FGF-23 and 1,25(OH)(2)D were observed. In SF associations between FGF-23 and fractional phosphate excretion, and FGF-23 and 1,25(OH)(2)D, were not observed. 1,25(OH)(2)D concentrations associated more weakly with FGF-23 in SF compared with C (P <0.05). CONCLUSIONS: Quantitative differences in serum Ca and 1,25(OH)(2)D and reductions in 24-hydroxylation of vitamin D metabolites are present in first-time SF and might contribute to first-time stone risk.