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J Ren Nutr. 2014 May ; 24(3): 186–193. doi:10.1053/j.jrn.2014.01.015.

Increasing Use of Vitamin D Supplementation in the Chronic


Renal Insufficiency Cohort Study
Laura H. Mariani, MD, MSCE*, Matthew T. White, PhD†, Justine Shults, PhD‡, Cheryl A. M.
Anderson, PhD, MPH§, Harold I. Feldman, MD, MSCE‡,¶, Myles Wolf, MD**, Peter P. Reese,
MD, MSCE‡,¶, Michelle R. Denburg, MD, MSCE††, Raymond R. Townsend, MD¶, Joan C. Lo,
MD‡‡, Anne R. Cappola, MD, ScM¶, Dean Carlow, MD††, Crystal A. Gadegbeku, MD§§,
Susan Steigerwalt, MD¶¶, Mary B. Leonard, MD, MSCE‡,††, and on behalf of the CRIC Study
Investigators
*University of Michigan Medical School and Arbor Research Collaborative for Health, Ann Arbor,
Michigan
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†The Clinical Research Center, Boston Children's Hospital, Boston, Massachusetts


‡Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of
Pennsylvania, Philadelphia, Pennsylvania
§University of California–San Diego School of Medicine, San Diego, California
¶Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia,
Pennsylvania
**Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida
††Department of Pediatrics, Perelman School of Medicine, and the University of Pennsylvania
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
‡‡Kaiser Permanente, Oakland, California
§§Temple University School of Medicine, Philadelphia, Pennsylvania
¶¶St. Johns Health System, Detroit, Michigan
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Abstract
Objective—This study examined rates and determinants of vitamin D supplementation among
Chronic Renal Insufficiency Cohort (CRIC) participants and determined the association between
dose and 25-hydroxyvitamin D (25(OH)D) level. The 2010 Institute of Medicine Report noted a
significant increase in vitamin D supplementation in the general population, but use in chronic
kidney disease (CKD) is unknown.

Methods—CRIC is a multicenter prospective observational cohort study of 3,939 participants


with a median baseline age of 60 and an estimated glomerular filtration rate (eGFR) of 42.1 mL/

© 2014 by the National Kidney Foundation, Inc. All rights reserved.


Address correspondence to Laura H. Mariani, MD, MSCE, University of Michigan, Division of Nephrology, Simpson Building,
Room 208, 102 Observatory Street, Ann Arbor, MI 48109. lmariani@umich.edu.
Financial Disclosure: The authors declare that they have no relevant financial interests.
Mariani et al. Page 2

minute per 1.73 m2. Of the cohort, 54.9% was male, 42.1% were Black, and 48.4% were diabetic.
Multivariable logistic generalized estimating equations were used to examine determinants of
supplementation use assessed annually between 2003 and 2011. Cross-sectional linear regression
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models, based on a subset of 1,155 participants, assessed associations between supplement dose
and 25(OH)D level, measured by high-performance liquid chromatography coupled with tandem
mass spectrometry.

Results—The proportion of participants reporting supplement use increased (P < .0001), from
10% at baseline to 44% at 7-year follow-up visits. This was largely due to initiation of products
containing only ergocalciferol or cholecalciferol. The odds of supplementation were greater in
older, female, non-Black, married participants with greater education and lower body mass index.
Among participants taking supplementation, dose was positively associated with 25(OH)D level,
adjusted for race, season, diabetes, dietary intake, eGFR, and proteinuria. Only 3.8% of non-Black
and 16.5% of Black participants taking a supplement were deficient (<20 ng/mL), whereas 22.7%
of non-Black and 62.4% of Black participants not reporting supplement use were deficient.

Conclusions—Vitamin D supplementation rates rose significantly among CRIC participants


over 7 years of follow-up and were associated with greater serum 25(OH)D levels. Studies of
vitamin D levels on clinical outcomes in CKD and future vitamin D interventional studies should
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consider these changes in supplementation practices.

Introduction
In recent years, the potential role of 25-hydroxyvitamin D (25(OH)D) deficiency in a wide
range of diseases has been increasingly recognized and widely publicized. These include
cardiovascular disease, malignancy, insulin resistance, diabetes, autoimmune disease,
infection, impaired physical function, fractures, and mortality.1 As a result of the increased
awareness of the potential importance of vitamin D status, the number of clinical assays of
25(OH)D levels and the use of calciferol supplementation has increased dramatically in the
general population, as reported in the 2010 Institute of Medicine (IOM) Report on Dietary
Reference Intakes for Calcium and Vitamin D.2 A recent population-based Canadian study
also reported secular increases in vitamin D supplementation use and 25(OH)D levels over
10 years.3 Trends of supplementation use among patients with chronic kidney disease
(CKD) are unknown.
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25(OH)D deficiency is common in CKD, especially non-Caucasian patients4 and those with
advanced disease.5 Recent studies in CKD linked 25(OH)D deficiency with
hyperparathyroidism, insulin resistance, anemia, inflammation, CKD progression, and
mortality.5-13 CKD is associated with a heavy burden of cardiovascular, metabolic, and
infectious complications, and 25(OH)D deficiency may be an important modifiable risk
factor. The 2003 Kidney Disease Outcomes Quality Initiative guidelines recommended
supplementation for CKD Stages 3 to 4 with hyperparathyroidism and a 25(OH)D level less
than 30 ng/mL.14 The 2009 Kidney Disease Improving Global Outcomes guidelines
recommended more expanded testing for all patients with CKD Stages 3 to 5 and treatment
strategies as in the general population without establishing a target level.15 Studies in the
general population suggest that large doses (>2,000 IU/day) are required to correct and
maintain adequate 25(OH)D levels.16,17 Compared with the general population, CKD

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patients have additional risk factors for 25(OH)D deficiency, including urinary losses of
vitamin D-binding protein and albumin, decreased 25(OH)D production by uremic skin in
response to ultraviolet B ray exposure,18 and decreased dairy intake due to phosphate
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restriction.

The objectives of this study were 2-fold. First, we examined vitamin D supplementation use
at annual visits among all Chronic Renal Insufficiency Cohort (CRIC) study participants to
identify determinants and trends of supplementation use. Second, we examined the cross-
sectional relationship between calciferol dose and serum 25(OH)D levels in a subset of
CRIC participants who completed a detailed assessment of vitamin D dose at a single visit.

Methods
Study Population
The CRIC study is a multicenter prospective observational study established by the National
Institute of Diabetes and Digestive and Kidney Diseases to examine risk factors for CKD
progression and cardiovascular disease.19 A total of 3,939 ethnically and racially diverse
participants, aged 21 to 74 years, with mild to moderate CKD were recruited from 2003 to
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2008 on the basis of age-specific estimated glomerular filtration rate (eGFR; 20-70 mL/
minute per 1.73 m2) at 7 clinical sites.20 The protocol was approved by the institutional
review board at each site. Participants provided informed consent.19-21

Data Collection
Detailed information regarding demographics, medical history, quality of life, health
behaviors, and physical activity were collected by research coordinator interview and
questionnaire at the baseline visit, as previously described.19

Blood and urine specimens were collected annually, and eGFR (mL/minute per 1.73 m2)
was calculated using the Modification of Diet in Renal Disease formula on the basis of
serum creatinine.22 Proteinuria was assessed by 24-hour urine collection.

Dietary information was collected at baseline and every other year using the National
Cancer Institute's Dietary History Questionnaire (DHQ). This validated instrument assesses
food frequency and amount in the past year to compute average daily nutrient intake,
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including vitamin D.23 The DHQ assesses usual dietary intake of 124 food items on the
basis of national dietary intake data from the 1994 to 1996 U.S. Department of Agriculture's
Continuing Survey of Food Intake in Individuals. After being manually reviewed for
completeness, DHQs were analyzed using the National Cancer Institute's DietCalc software.
Approximately 10% of DHQs were excluded because unlikely values were reported for total
energy intake (i.e., <600 or >4,000 kcal for women and <800 or >5,000 kcal for men).

Medication use was assessed at each annual visit by research coordinator interview and
completion of the Concomitant Medication (CMED) form. Participants were asked to bring
a list of their medications and supplements taken in the prior 30 days. Name, dose, units, and
frequency were recorded and matched to drug codes from the Medication Reference Tool in
the data management system. A total of 72 drug codes identified a medication or supplement

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that contained any amount of either vitamin D2 (ergocalciferol) or D3 (cholecalciferol). If


participants reported use of any of these products, then they were classified as taking a
calciferol at that visit. Given the many multinutrient supplements, dose data were not
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available for the calciferol component.

A subset of the full CRIC cohort at 4 selected clinical centers completed a single visit
between 2008 and 2010 at the time of physical function testing in which augmented
procedures were used to obtain detailed vitamin D intake. Research coordinators at these
sites were trained to elicit a detailed vitamin D supplementation history using the Vitamin D
Concomitant Medication (DCMED) form, in addition to the CMED form, at this visit.
Participants were asked to bring medication and supplement bottles to record formulation,
frequency, route, and calciferol content of all calciferol-containing medications used in the
prior 3 months.

In the subset that completed this DCMED form, stored serum specimens from the same visit
were used to measure 25(OH)D levels by high-performance liquid chromatography coupled
with tandem mass spectrometry. This assay gave a linear response from 1.3 to 135 ng/mL
for 25(OH)D2 and 25(OH)D3 and the limit of quantitation (signal-to-noise ratio ≥ 10) was
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1.3 ng/mL. The interassay coefficients of variation were 7.3% to 10.0% and 4.2% to 4.9%
for 25(OH)D2 and 25(OH)D3, respectively. The specimens were collected and run at the end
of the study; thus, they were not available to the participants or research team at each site.

Statistical Analysis
Descriptive statistics, including mean and standard deviation for normally distributed
variables, median and inter-quartile range (IQR) for skewed variables, and proportions for
categorical variables, were used to characterize baseline participant characteristics and
supplementation use at each visit.

Two primary analyses were conducted. First, in the full cohort of participants, a
multivariable logistic generalized estimating equation model was fit to identify determinants
of supplementation use. Study visits after transplantation or initiation of dialysis were
excluded. Because of concern for greater ascertainment of calciferol supplementation among
participants at clinical centers using the DCMED form, we compared supplementation use
before and after research coordinators from these sites were trained to use the DCMED form
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and to clinical centers using the CMED form. Using a piecewise logistic regression analysis,
we found that neither the log odds of supplementation (P = .829) nor the rate of change in
supplementation (P = .727) at DCMED centers increased more immediately after DCMED
training than at CMED centers. Therefore, study visits after training were included, and
sensitivity analyses excluding these visits did not alter results.

Potential determinants of supplementation included age, sex, race, ethnicity, diabetes,


socioeconomic status (income, education, and marital status), lifestyle variables (smoking,
physical activity, and body mass index [BMI]), cause of CKD, proteinuria, eGFR, having
seen a nephrologist before the baseline visit, calendar year, and study year.

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The second primary analysis was performed in the subset of the cohort that had both dose
information and levels available. Spearman's rank correlation coefficient (ρ) was used to
separately assess the relationship between supplementation dose and 25(OH)D level for
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Black and non-Black participants. Linear regression was used to examine the association
between 25(OH)D level and calciferol supplementation dose, adjusted for determinants of
25(OH)D level, including age, sex, race, ethnicity, physical activity (a surrogate for sun
exposure), BMI, diabetes, proteinuria, socioeconomic status, dietary vitamin D, and eGFR.
Because 25(OH)D level was logarithmically transformed for anal ysis, results were
presented as the percentage difference in predicted level compared with the reference
category. The exponentiated regression coefficient for a particular covariate represents the
ratio of 25(OH)D level for that category relative to the reference category. Analyses were
performed using Stata, version 11.2 (College Station, TX), with 2-sided tests of hypotheses
and a P value less than .05 as the criterion for statistical significance.

Results
Trends in Vitamin D Supplementation Use Among All CRIC Participants
The baseline characteristics of the 3,939 CRIC participants are summarized in Table 1. The
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median duration of follow-up was 5 (IQR 3-6) years with a total of 20,983 visits. Among all
participants, rates of reported use of any product containing a calciferol increased
dramatically according to calendar and study year (Fig. 1). Use increased with longer
participation in CRIC, from 10% at the baseline visits to 44% at the 7-year visits. Similar
trends were observed in analyses limited to the 708 participants with 7 years of follow-up.
Supplementation increased with later calendar year, from 10% at visits in 2003 to 43% at
visits in 2011. The increase was primarily driven by use of products containing
ergocalciferol or cholecalciferol alone, whereas use of products containing calcium and
calciferol increased less markedly (Fig. 2). Use of active vitamin D sterols remained stable
at 2% to 3% over this same time period. The predominant formulation of calciferol switched
from ergocalciferol (69.3% of supplements in 2003) to cholecalciferol (77.2% of
supplements in 2010).

Predictors of Vitamin D Supplement Use Among All CRIC Participants


The full cohort was used to identify predictors of supplementation use. The results of the
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multivariable logistic generalized estimating equation regression are shown in Table 2.


Greater odds of supplementation were associated with older age, female gender, non-Black
race, higher education level, married, and lower BMI. Visit number and calendar year were
independent predictors. Having seen a nephrologist, stage and cause of CKD, degree of
protein-uria, income level, reported exercise, and smoking status were not independent
predictors.

25(OH)D Levels in a Subset of CRIC Participants


Vitamin D levels and a detailed assessment of vitamin D intake were available in a subset of
participants as part of a cross-sectional study of physical function and vitamin D status in
CRIC. The characteristics of participants who completed this single visit are shown in Table
3. Overall, 524 (54.6%) of participants reported taking at least 1 product that contained

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ergocalciferol or cholecalciferol in the preceding 3 months. Many were taking more than 1
vitamin D product. Among participants who reported supplementation, the median dose was
500 (IQR 400-1000) IU/day.
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Figure 3 demonstrates the associations between 25(OH) D level and calciferol


supplementation according to race. Dose category was positively associated with vitamin D
level for Black (ρ = 0.57, P<.0001) and non-Black participants (ρ = 0.45, P<.0001). As
expected, among participants taking 400 IU/day or less of calciferol, Black participants had
significantly lower median 25(OH)D levels (19.3 ng/mL [IQR 13.5, 30.9]) compared with
non-Black participants (31.6 ng/mL [IQR 22.8, 41.0]; P< 001). However, among
participants taking more than 400 IU/day, the race difference was not evident (P = .17): the
median 25(OH)D level was 42.0 ng/mL (IQR 35.2, 49.7) for non-Black and 40.5 ng/mL
(IQR 32.3, 50.4) for Black participants. Overall, 11.2% of non-Black and 41.8% of Black
participants had a deficient level (<20 ng/mL). However, among those taking any
supplement, only 3.8% of non-Black and 16.5% of Black participants were deficient
whereas 22.7% of non-Black and 62.4% of Black participants not reporting supplement use
were deficient.
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There was a significant dose response relationship between supplementation use and
25(OH)D level adjusted for race, season, diabetes, dietary vitamin D, proteinuria, and eGFR.
The results of the linear regression model are presented in Table 4. The effect of
supplementation (>400 IU/day) was greater than any other predictors in the model. There
was a significant interaction between Black race and supplementation use as indicated by the
relatively greater increase in level for each vitamin D dose among the Black participants. In
contrast, there was no interaction between CKD stage or supplement type (calcium-
containing vs. vitamin D alone) and supplementation dose in its association with 25(OH)D
level. Physical activity, BMI, cause of CKD, sex, age, and smoking status were not
independent predictors of 25(OH)D level.

When total daily dose of calciferol was separated by formulation in this model, 1,000 IU of
cholecalciferol was associated with a 29.0% higher 25(OH)D level as compared with no
supplementation (P < .001); 1,000 IU of ergocalciferol was associated with a 14.7% higher
25(OH)D level as compared with no supplementation (P = .008), consistent with a lower
potency.
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When models were fit for 25(OH)D2 and 25(OH)D3 levels separately, greater daily
cholecalciferol (D3) dose was associated with greater 25(OH)D3 levels (P < .001) whereas
greater daily ergocalciferol (D2) dose was associated with greater 25(OH)D2 levels (P < .
001).

Discussion
Reported use of calciferol supplements increased markedly in the CRIC cohort over time,
primarily because of increased use of single-nutrient products containing ergo-calciferol or
cholecalciferol. Supplementation was associated with markedly greater vitamin D levels,
especially among Black participants. To our knowledge, this is the first study to examine

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trends in vitamin D supplementation in CKD and to relate supplement dose to vitamin D


levels. These findings have important implications for future vitamin D intervention studies
and for the interpretation of observational studies of vitamin D levels and clinical outcomes
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in CKD. Specifically, the increasing prevalence of vitamin D supplementation in CKD


patients may make it difficult to identify, and thus enroll, patients with deficient levels and
to control the rates of supplementation use in a trial setting. Further, observational studies
relying on a single vitamin D level may be affected by this increasing prevalence of
supplementation use. The results of a recently published meta-analysis and accompanying
editorial24,25 on vitamin D supplementation and fracture prevention in the general
population highlight the importance of accounting for actual intake and baseline vitamin D
status when trying to reconcile discordant results from clinical trials.

There was a wide range of daily vitamin D dosage. The 2010 IOM report recommended 600
IU/day for people younger than 70 years of age and 800 IU/day for people older than 70
years of age with a maximum tolerated dose of 4,000 IU/day.2 Among CRIC participants
taking a supplement, the median dose was 500 IU per day, and 1% of participants were
taking 4,000 IU/day or more. Median dietary vitamin D intake was 112 IU/day and did not
differ among those participants who were or were not taking a supplement. This is much
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lower than the median intake reported in the IOM report for the general population, which
ranges from 272 to 396 IU/day depending on life stage and may be related to phosphorus
restriction with consequent reductions in dairy intake.

One could hypothesize that there would be minimal association between supplement dose
and level in a cross-sectional analysis because patients would be a combination of those
prescribed vitamin D because of severe deficiency with those who were taking a supplement
regardless of level. However, our analysis reveals that supplement use was associated with
significantly higher vitamin D levels, with a dose-response relationship, and had a stronger
association than any other factor in the model. A recent study reported that supplementation
use was an important predictor of vitamin D levels in a healthy, northern European
population26; however, this had not been previously assessed in patients with CKD.
Furthermore, this is the first study to examine racial differences in the relationship between
vitamin D supplementation and levels. Longitudinal measures of vitamin D levels were not
available to assess the response to supplementation or baseline levels. However, it was
surprising to note that even modest doses of supplementation were associated with higher
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levels.

Two large previous reports have demonstrated mixed results regarding the relationship
between 25(OH)D levels and eGFR. Chonchol and colleagues analyzed data from the Third
National Health and Nutrition Examination Survey and showed that 25(OH)D levels were
low only among those with advanced CKD (eGFR 15-29 mL/min ute per 1.73 m2) after
adjustment for age, sex, ethnicity, BMI, physical activity, intake of milk and vitamin D
supplements, and season.5 However, in the Study to Evaluate Early Kidney Disease, Levin
and colleagues reported no relationship between 25(OH)D level and eGFR after adjustment
for age, gender, ethnicity, diabetes, urinary albumin, calcium, and phosphorus.27 Our study
obtained detailed information regarding supplement use and dose, which we also
demonstrated to be highly prevalent and an important predictor of level. Although

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unadjusted analysis suggested an association of lower 25(OH)D levels with lower eGFR,
this association did not persist after adjusting for supplement use dosage, dietary intake,
season, diabetes, and proteinuria. In fact, lower eGFR was associated with a slightly higher
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level in our full model. In this cross-sectional analysis, we were not able to assess changes in
eGFR or changes in 25(OH)D level.

A limitation of the study is reliance on self-report of supplementation use. However, review


of reported calciferol supplement formulations over time revealed a switch from D2-
(ergocalciferol) to D3 (cholecalciferol)-containing products, consistent with national trends
among vitamin D supplement manufacturers.2 In addition, the strong association between
reported supplementation and serum vitamin D levels as well as the association between
reported vitamin D formulation and the respective D2- and D3-specific levels provided
additional evidence for the validity of the data. Self-report of ultraviolet sun exposure as a
source of vitamin D was not directly collected, but season and activity level were included.
Detailed information on calcium supplementation dose was also not available.

Levels and dose information were only available for a subset of CRIC participants at
selected clinical centers that used augmented techniques to collect information on
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supplementation use. All participants at these clinical centers were eligible to collect these
supplemental data, and 86% did so. These high participation rates make selection bias
unlikely. These study participants were somewhat healthier compared with the remainder of
the CRIC cohort. This likely reflects survival to this later visit (87% of visits were
performed 3-5 years after enrollment) and varying baseline participant characteristics of the
participating clinical sites. Given that the primary goal was to relate supplement dose and
vitamin D level, it is unlikely that these differences introduced a significant bias.

Because detailed vitamin D dose information and 25(OH)D levels were available only at a
single visit, our current data could not assess the longitudinal effect of vitamin D
supplementation and changes in parathyroid hormone or other bone mineral metabolism
laboratory values such as calcium and phosphorus. Future studies will be needed to assess
this relationship as well as the association with clinical outcomes such as fracture.

Practical Application
This study revealed an increasing use of calciferol supplementation among participants in
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the CRIC study and that supplementation use was associated with greater 25(OH)D levels.
Predictors of supplementation use included socioeconomic factors in addition to expected
demographic factors. Given the recent call for interventional trials using nutritional vitamin
D,2 these results demonstrate the challenges of completing these studies, especially because
these participants are likely representative of other individuals who would be recruited for
future clinical trials; specifically, a large and increasing proportion of CKD patients are
taking vitamin D and that this supplementation use is associated with high levels.

Acknowledgments
Support: This CRIC ancillary study was supported by National Institutes of Health grants R01DK077128 and
K24DK076808 (M.B.L.); cooperative agreement project grants 5U01DK060990, 5U01DK060984, 5U01DK06102,
5U01DK061021, 5U01DK061028, 5U01DK60980, 5U01DK060963, and 5U01DK060902 from the National

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Institute of Diabetes and Digestive and Kidney Diseases; and grants UL1RR024134, UL1RR025005,
M01RR16500, UL1RR024989, M01RR000042, UL1RR024986, UL1RR029879, RR05096, and UL1RR024131
from the National Institutes of Health.
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26. Zgaga L, Theodoratou E, Farrington SM, et al. Diet, environmental factors, and lifestyle underlie
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27. Levin A, Bakris GL, Molitch M, et al. Prevalence of abnormal serum vitamin D, PTH, calcium,
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Figure 1.
Trends in calciferol supplementation use in the CRIC study over time. Patients reporting a
calciferol-containing supplement on the CMED at 19,503 annual visits of the full cohort of
CRIC participants from 2003 to 2011. CMED, Concomitant Medication form; CRIC,
Chronic Renal Insufficiency Cohort.
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Figure 2.
Trends in type of calciferol supplementation use. Patients reporting a calciferol-containing
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supplement on the CMED at 19,503 annual visits of the full cohort of CRIC participants
from 2003 to 2011. CMED, Concomitant Medication form; CRIC, Chronic Renal
Insufficiency Cohort.
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Figure 3.
Vitamin D level by reported daily supplement dosage for Black and non-Black participants.
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Data from 1,155 participants who completed a single study visit to obtain detailed vitamin D
intake history at the time of physical function testing, collected using the DCMED. Dashed
reference line at 20 ng/mL, below which is considered deficient. Spearman test for trend
with P < .001 for Black and non-Black participants. DCMED, Vitamin D Concomitant
Medication form.
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Table 1

Baseline Participant Characteristics of Full Cohort (N = 3,939)


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Age (y) 60 (52, 66)


Male 54.9%
Black 42.1%
Diabetes 48.4%
Smoking 13.1%
Any intentional exercise 69.8%
Married 54.8%
eGFR (mL/min per 1.73 m2) 42.1 (32.6, 51.9)
>60 10.3%
30-60 70.2%
<30 19.5%
Proteinuria (g/24 h) 0.18 (0.07, 0.91)
<1.5 81.6%
≥1.5 18.4%
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BMI (kg/m2) 30.9 (26.8, 36.1)


<25 16.0%
25 to <30 28.6%
30 to <35 26.2%
≥35 29.3%
Education
less than high school 21.0%
High-school graduate 18.8%
Some college 29.2%
College graduate 31.0%
Income
≤$20,000 31.5%
$20,000-50,000 24.4%
$50,000-100,000 18.7%
>$100,000 10.0%
Did not answer 15.5%
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BMI, body mass index; eGFR, estimated glomerular filtration rate.


All characteristics were recorded at the participants’ baseline study visits, conducted from 2003 to 2008. Continuous variables are presented as
median (interquartile range). Categorical variables are presented as percentages.

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Table 2

Results of Multivariable Logistic Generalized Estimating Equation Model of Calciferol Supplementation Use
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Determinant OR (95% CI) P


Age (per 10 y) 1.30 (1.23, 1.37) <.001
White race 1.54 (1.36, 1.74) <.001
Female sex 3.00 (2.66, 3.37) <.001
Married 1.15 (1.03, 1.29) .016
Education
Less than high school 1.0 (Reference)
High-school graduate 1.51 (1.24, 1.84) <.001
Some college 1.53 (1.28, 1.85) <.001
College graduate 1.77 (1.47, 2.14) <.001
BMI (kg/m2)
<25 1.0 (Reference)
25 to <30 0.75 (0.64, 0.88) <.001
30 to <35 0.72 (0.61, 0.85) <.001
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≥35 0.65 (0.55, 0.77) <.001


Visit number 1.12 (1.06, 1.18) <.001
Calendar year 1.21 (1.15, 1.27) <.001

BMI, body mass index; CI, confidence interval; OR, odds ratio.
Data from full cohort (N = 3,531) with a total of 19,019 annual visits and adjusted for clinical site.
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Table 3

Characteristics of Participants Enrolled in the Vitamin D Ancillary Study (n = 1,155)


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Age (y) 64 (57, 70)


Male 53.0%
Black 35.5%
Diabetes 37.1%
Smoking 7.5%
Any intentional exercise 79.8%
Married 61.6%
eGFR (mL/min per 1.73 m2) 44.8 (33.8,54.8)
>60 15.0%
30-60 66.5%
<30 18.5%
Proteinuria (g/24 h) 0.16 (0.08, 0.63)
<1.5 88.3%
≥1.5 11.72%
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BMI (kg/m2) 29.9 (26.1, 34.7)


<25 18.5%
25 to <30 32.1%
30 to <35 25.6%
≥35 23.8%
Education
Less than high school 7.1%
High-school graduate 14.2%
Some college 29.2%
College graduate 49.6%
Income
≤$20,000 12.9%
$20,000-50,000 25.5%
$50,000-100,000 28.1%
>$100,000 19.0%
Did not answer 14.6%
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Visit calendar year


2008 41.7%
2009 57.1%
2010 1.1%
Number of calciferol-containing medications
0 45.4%
1 40.5%
2 12.3%
3 1.5%
4 0.4%

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Calciferol dose if taking ≥1 calciferol-containing medications (IU/d) 500 (400, 1000)


Dietary vitamin D intake (IU/d) 112 (72, 175)
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25(OH)D level (ng/mL) Black Non-Black


If taking 0 calciferol-containing medications 16.9 (12.1, 26.3) 27.7 (20.6, 38.5)
If taking ≥1 calciferol-containing medications 35.4 (25.8, 45.5) 38.8 (32.2, 47.1)

BMI, body mass index; DCMED, Vitamin D Concomitant Medication form; eGFR, estimated glomerular filtration rate; 25(OH)D, 25-
hydroxyvitamin D.
All characteristics were recorded at the participants’ vitamin D study visit (2008-2010) when augmented procedures and DCMED form were used
to assess supplementation use. Continuous variables are presented as median (interquartile range). Categorical variables are presented as
percentages.
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Table 4

Results of Linear Regression of 25(OH)D Levels (n = 1,021)


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Determinant Relative Percent Change Compared With Reference Group (95% CI)
Vitamin D supplement (IU/d) Non-Black Black
0 Reference Reference
>0-400 26.5% (16.9, 36.9)* 60.8% (43.8, 79.9)*
>400-800 46.4% (32.3, 62.0)* 125.8% (92.2, 165.2)*
>800 61.0% (47.6, 75.7)* 127.1% (96.9, 161.9)*
Season
Summer Reference
Winter –11.1% (–15.8, –6.1)
Marital status
Not married Reference
Married 7.9% (2.1, 14.0)†
Dietary vitamin D (IU/d)
<200 Reference
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≥200 7.7% (0.7, 15.2)†


Diabetes
No Reference
Yes –11.8% (–16.5, –6.7)*
Proteinuria (g/d)
<1.5 Reference
≥1.5 –17.9% (–24.8, –10.3)*
eGFR (mL/min per 1.73 m2)
>60 Reference
30-60 13.6% (5.4, 22.6)*
<30 13.7% (3.2, 25.2)†
Serum albumin (mg/dL)
<3.5 Reference
≥3.5 to <4 10.6% (0.2, 22.1)†
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≥4 20.8% (9.4, 33.3)*

CI, confidence interval; eGFR, estimated glomerular filtration rate; 25(OH)D, 25-hydroxyvitamin D.
Data from subset cohort that completed a single vitamin D study visit, and augmented procedures were used to assess vitamin D supplement use (n
= 1,155).
*
P ≤ .001.

P < .05.

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