title: Calcium and phosphorus regulatory hormones and risk of incident symptomatic kidney stones.
abstract: OBJECTIVE
  Calcium and phosphorus regulatory hormones may contribute to the pathogenesis of calcium nephrolithiasis. However, there has been no prospective study to date of plasma hormone levels and risk of kidney stones. This study aimed to examine independent associations between plasma levels of 1,25-dihydroxyvitamin D (1,25[OH]2D), 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, fibroblast growth factor 23 (FGF23), parathyroid hormone, calcium, phosphate, and creatinine and the subsequent risk of incident kidney stones.
  
  
  METHODS
  This study was a prospective, nested case-control study of men in the Health Professionals Follow-Up Study who were free of diagnosed nephrolithiasis at blood draw. During 12 years of follow-up, 356 men developed an incident symptomatic kidney stone. Using risk set sampling, controls were selected in a 2:1 ratio (n=712 controls) and matched for age, race, and year, month, and time of day of blood collection.
  
  
  RESULTS
  Baseline plasma levels of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, parathyroid hormone, calcium, phosphate, and creatinine were similar in cases and controls. Mean 1,25(OH)2D and median FGF23 levels were higher in cases than controls but differences were small and statistically nonsignificant (45.7 versus 44.2 pg/ml, P=0.07 for 1,25[OH]2D; 47.6 versus 45.1 pg/ml, P=0.08 for FGF23). However, after adjusting for body mass index, diet, plasma factors, and other covariates, the odds ratios of incident symptomatic kidney stones in the highest compared with lowest quartiles were 1.73 (95% confidence interval, 1.11 to 2.71; P for trend 0.01) for 1,25(OH)2D and 1.45 (95% confidence interval, 0.96 to 2.19; P for trend 0.03) for FGF23. There were no significant associations between other plasma factors and kidney stone risk.
  
  
  CONCLUSIONS
  Higher plasma 1,25(OH)2D, even in ranges considered normal, is independently associated with higher risk of symptomatic kidney stones. Although of borderline statistical significance, these findings also suggest that higher FGF23 may be associated with risk.
authors.affiliation: Channing Division of Network Medicine and Division of Nephrology and Transplantation, Maine Medical Center, Portland, Maine; entaylor@partners.org.
authors.forename: Eric N
authors.initials: EN
authors.lastname: Taylor
authors.affiliation: Departments of Medicine and Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington; and.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Hoofnagle
authors.affiliation: Channing Division of Network Medicine and Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Gary C
authors.initials: GC
authors.lastname: Curhan
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002118:Calcium / Q000097:blood*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D006728:Hormones / Q000097:blood*; D006801:Humans; D015994:Incidence; D007669:Kidney Calculi / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010758:Phosphorus / Q000097:blood*; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D006728:Hormones; D014807:Vitamin D; D010758:Phosphorus; D005346:Fibroblast Growth Factors; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23; D002118:Calcium
keywords: fibroblast growth factor 23; kidney stones; nephrolithiasis; risk factors; vitamin D