Altered Calcium and Vitamin D Homeostasis in First-Time Calcium Kidney Stone-Formers.
BACKGROUND
Elevated serum 1,25-dihydroxyvitamin D (1,25(OH)2D) 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)2D, 24,25-dihydroxyvitamin D (24,25(OH)2D), 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)2D 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)2D/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)2D, FGF-23 and fractional phosphate excretion, and negative associations between serum Ca and PTH, and FGF-23 and 1,25(OH)2D were observed. In SF associations between FGF-23 and fractional phosphate excretion, and FGF-23 and 1,25(OH)2D, were not observed. 1,25(OH)2D 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)2D and reductions in 24-hydroxylation of vitamin D metabolites are present in first-time SF and might contribute to first-time stone risk.
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States of America; Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States of America; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America.
Hemamalini
H
Ketha
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.
Ravinder J
RJ
Singh
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America.
Stefan K
SK
Grebe
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.
Eric J
EJ
Bergstralh
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States of America; Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States of America; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.
Andrew D
AD
Rule
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States of America; Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States of America; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America.
John C
JC
Lieske
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States of America; Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States of America; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, United States of America.
Rajiv
R
Kumar
D000328:Adult; D002118:Calcium / Q000378:metabolism*; D015331:Cohort Studies; D004872:Ergocalciferols / Q000378:metabolism*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D006706:Homeostasis; D006801:Humans; D007669:Kidney Calculi / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D004872:Ergocalciferols; C000717427:FGF23 protein, human; C003564:1,25-dihydroxyergocalciferol; D000089703:Fibroblast Growth Factor-23; D002118:Calcium