Biomarkers of Vitamin D Status and Risk of ESRD

Casey M. Rebholz, Morgan E. Grams, Pamela L. Lutsey, Andrew N. Hoofnagle, Jeffrey R. Misialek, Lesley A. Inker, Andrew S. Levey, Elizabeth Selvin, Chi yuan Hsu, Paul L. Kimmel, Ramachandran S. Vasan, John H. Eckfeldt, Josef Coresh

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26 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)235-242
Number of pages8
JournalAmerican Journal of Kidney Diseases
Issue number2
StatePublished - Feb 1 2016

Bibliographical note

Funding Information:
Support: The ARIC Study is carried out as a collaborative study supported by National Heart, Lung and Blood Institute (NHLBI) contracts ( HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C ). This work was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant R01DK089174 (Principal Investigator: E. Selvin) and NHLBI grant R01HL103706 (Principal Investigator: P. Lutsey). Additional support is provided by U01DK085689 from the NIDDK (Chronic Kidney Disease Biomarkers Consortium). The study sponsors had no role in study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication.

Publisher Copyright:
© 2016 National Kidney Foundation, Inc.


  • Biological markers
  • Vitamin D
  • Vitamin D insufficiency
  • Vitamin D-binding protein
  • chronic renal failure
  • end-stage renal disease (ESRD)
  • mineral metabolism biomarker
  • risk factors


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