Casey M Rebholz1, Morgan E Grams2, Pamela L Lutsey3, Andrew N Hoofnagle4, Jeffrey R Misialek3, Lesley A Inker5, Andrew S Levey5, Elizabeth Selvin6, Chi-Yuan Hsu7, Paul L Kimmel8, Ramachandran S Vasan9, John H Eckfeldt10, Josef Coresh6. 1. Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. Electronic address: crebhol1@jhu.edu. 2. Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Division of Nephrology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD. 3. Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN. 4. Department of Laboratory Medicine, University of Washington, Seattle, WA. 5. William B. Schwartz Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA. 6. Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Division of General Internal Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD. 7. Division of Nephrology, Department of Medicine, University of California, San Francisco School of Medicine, San Francisco, CA. 8. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. 9. Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, MA; Section of Cardiology, Department of Medicine, Boston University School of Medicine, Boston, MA. 10. Department of Laboratory Medicine and Pathology, University of Minnesota School of Medicine, Minneapolis, MN.
Abstract
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.
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.
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