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 (1996-1998) of the ARIC (Atherosclerosis Risk in Communities) Study. Outcome ESRD cases (n = 184) were identified through hospitalization diagnostic codes from 1996 to 2008 and were frequency matched to controls (n = 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 = 0.003). Higher free and bioavailable 25(OH)D levels were associated with reduced risk for incident ESRD (ORs of 0.65 [95% CI, 0.46-0.92; P = 0.02] and 0.63 [95% CI, 0.43-0.91; P = 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 = 0.3) or 1,25(OH)₂D (OR, 0.73; 95% CI, 0.48-1.13; P = 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.