Original Investigation Biomarkers of Vitamin D Status and Risk of ESRD

Background: Disordered mineral metabolism is characteristic of decreased kidney function. However, the prospective associations between circulating levels of vitamin D binding protein, vitamin D, and end-stage renal disease (ESRD) have not been extensively evaluated in epidemiologic studies. Study Design: Nested case-control study. Setting & Participants: Middle-aged black and white men and women from 4 US communities. Predictors: Baseline levels of vitamin D binding protein, 25-hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D (1,25[OH]2D) were measured in blood samples collected at study visit 4 (19961998) of the ARIC (Atherosclerosis Risk in Communities) Study. Outcome: ESRD cases (n 5 184) were identified through hospitalization diagnostic codes from 1996 to 2008 and were frequency matched to controls (n 5 251) on categories of estimated glomerular filtration rate, albuminuria, diabetes mellitus, sex, and race. Measurements: Logistic regression was used to estimate the association between mineral metabolism biomarkers (vitamin D binding protein, 25(OH)D, and 1,25(OH)2D) and incident ESRD, adjusting for age, sex, race, estimated glomerular filtration rate, albuminuria, diabetes mellitus, hypertension, education, specimen type, and serum levels of calcium, phosphate, and parathyroid hormone. Results: Higher vitamin D binding protein levels were associated with elevated risk for incident ESRD (OR, 1.76;95%CI, 1.22-2.54;P 5 0.003).Higher freeandbioavailable25(OH)Dlevels wereassociatedwithreduced risk for incident ESRD (ORs of 0.65 [95% CI, 0.46-0.92; P 5 0.02] and 0.63 [95% CI, 0.43-0.91; P 5 0.02] for free and bioavailable 25[OH]D, respectively). There was no association between ESRD and overall levels of 25(OH)D (OR, 0.83; 95% CI, 0.58-1.19; P 5 0.3) or 1,25(OH)2D (OR, 0.73; 95% CI, 0.48-1.13; P 5 0.2). Limitations: Lack of direct measurement of free and bioavailable vitamin D. Conclusions: In the general population, blood levels of vitamin D binding protein were positively associated and blood levels of free and bioavailable 25(OH)D were inversely associated with new-onset ESRD during follow-up.