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Emily Wolf October 27, 2011


Introduction/Review of Literature Study Purpose Methods Results Discussion

Introduction to Vitamin D

Fat soluble vitamin Found in fish oil, fortified foods Best obtained by UV sunlight Important role in bone health Influences many genes Activated by two hydroxylations

vitamin D in liver 1,25(OH)2 vitamin D in kidney

The Many Consequences of Vitamin D Deficiency

Holick, MF

Digestion and Absorption of Vitamin D

Assessing Vitamin D

Liquid chromatography mass spectrometry Most accurate indicator of status is 25(OH) vitamin D
ng/mL <12 12-20 Health Status Vitamin D deficiency, leads to rickets and osteomalacia Considered inadequate for bone and overall health in healthy individuals

nmol/L <30 30-50



Considered adequate for bone and overall health in healthy individuals

Potentially adverse effects may occur
Institute of Medicine, 2011

Current RDA for Vitamin D

Age 0-12 months 1- 13 years 14-18 years 19 -70 years >70 years 400 IU 600 IU 600 IU 600 IU 800 IU

Male 400 IU 600 IU 600 IU 600 IU 800 IU


Institute of Medicine, 2011

Vitamin D Deficiency

Skeletal diseases
Osteomalacia Osteoporosis

Non-skeletal diseases
Hypertension Type

II diabetes mellitus Cancer and cardiovascular mortality MS, RA, IBD

Vitamin D and Bone Health

Linus Pauling Institute,2011

Vitamin Ds Other Role

Influences genes that


cancer cell proliferation Decrease renin production Increase insulin production Decrease inflammatory markers often seen in CVD

Who is at Risk?

Estimated 1 billion people worldwide at risk of developing deficiency Up to 90% of U.S. population deficient NHANES III identified obese individuals, African-Americans and Hispanics as higher risk Older adults

Conditions that Impair Vitamin D Metabolism and Absorption

Old age Location in relation to the sun IBD Liver disease CKD

Chronic Kidney DiseasePathophysiology

National Kidney Foundations Definition

Damage to the kidneys resulting in GFR of less than 60 mL per minute per 1.73m2 over a period longer than 3 months GFR: filtrate formed/minute

Conditions related to CKD

Hypertension T2DM CVD

High BUN Low creatinine clearance Proteinurea/Albuminurea

National Kidney Foundation, 2003

5 Stages of CKD

Stage Stage 1 Stage 2

Characterzed By Kidney damage with normal or elevated GFR Mild decrease in GFR

Stage 3
Stage 4 Stage 5

Moderate decrease in GFR

Severe decrease in GFR Kidney failure, need for dialysis

National Kidney Foundation, 2002

Who is Impacted by CKD?

Comorbidities associated with obesity


hyperlipidemia, hypertension

Older adults

of worlds population over 65 years old Prevalence of obesity in older adults in the U.S. is over 30% Comorbidities of obesity make this group very susceptible

CKD, T2DM and Obesity

Pima Indians of Arizona


et al, 1988 5056 Pima Indians from 1975-1986 Observed 80 incident cases of CKD, all but 2 attributable to T2DM Incidence of CKD increased with hypertension

Treating CKD

Early treatment can halt progression In early stages, treat comorbidities

Regulate blood pressure with ACE inhibitors Maintain glycemic control- Hb A1C under 7% Maintain lipid levels with statins Lifestyle modification

In end stage, patient is put on dialysis

Temporary or chronic Hemodialysis Peritoneal dialysis

Vitamin D and CKD

Failing kidneys are unable to hydroxylate 25(OH) vitamin D

Enzyme needed is regulated by PTH and low phosphate Inability to excrete phosphate results in hyperphosphatemia

25(OH) vitamin D lost in urine

Caused by proteinurea Excrete large amounts of 25(OH) vitamin D bound to VDBP

Current Vitamin D Recommendations for CKD Patients

NKF Clinical Practice Guidelines


vitamin D should be tested when PTH is above target range If serum level is below 30 ng/mL, supplement with active sterol Helps to lower PTH Important to check calcium and phosphorous levels Different cut offs:

D sufficient Vitamin D insufficient Vitamin D deficient

Prevalence of Vitamin D Deficiency in CKD

Levin et al, 2007

Health Benefits of Optimal Vitamin D in CKD

Vitamin D deficiency complicates CKD

Low levels associated with increased mortality

Kovesdy et al, 2008

Examined whether oral calcitriol would decrease incidence of mortality and need for dialysis in earlier stage CKD patients Supplemented 258 out of 520 subjects Found incidence of both was less in the supplemented group

Stubbs et al, 2010

Supplemented ESRD patients with cholecalciferol Found it effective at raising 1,25(OH)2D Decreased inflammatory cytokine levels

Study Purpose and Research Aims

1. Assess the prevalence of vitamin D deficiency in patients about to be put on dialysis in a long term acute care hospital 2. Examine characteristics of the patients

differences between groups organized by level of deficiency Identify risk factors associated with deficiency



56 patients starting hemodialysis at the Drake Center from June 2009-December 2010 Treated by Dr. Patrick McCullough 42 ESRD patients and 14 patients with acute kidney damage
Baseline data from a clinical trial Participants separated into 3 groups according to serum 25(OH)D

Research Design

Group 1: Vitamin D sufficient (30 ng/mL) Group 2: Vitamin D insufficient (10-29 ng/mL) Group 3: Vitamin D deficient (<10 ng/mL)

Differences explored between the 3 groups

Biochemical Assessment

Vitamin D
25(OH)D 1,25(OH)2D Radioimmunoassay 32-100 ng/mL

Vitamin D regulates calcium in the body Complexone and arsenazo III dye 8.9-10.4 mg/dL

Carrier protein for calcium, typically lost in urine in CKD Bromocresol or green dye binding method 3.6-5.1 g/dL

Regulates hydroxylation in the kidney Direct measurements 7.5-53.5 pg/mL ESRD target=150300 pg/mL

Other Assessments

Supplemental Use Other major diagnoses

T2DM Hypertension Hyperlipidemia Other

miscellaneous diagnoses

Age Sex Race

Statistical Analysis

Statistical Analysis Software for Windows Assessed frequency of each variable

Proportions calculated for categorical variables Mean and SD calculated for continuous variables

Differences between the three groups

Fishers exact test One way analysis of variance (ANOVA) Tukey method Further assessment of the number of patients within normal range for each biochemical assessment P<.05

Results: 25(OH) Vitamin D Deficiency

Prevalence of vitamin D insufficiency/deficiency


D sufficient (Group 1): 7% (N=4) Vitamin D insufficient (Group 2): 48% (N=27) Vitamin D deficient (Group 3): 45% (N=25)
0.5 0.4 Frequency 0.3 0.2 0.1 0 0 10 20 30 25(OH)D (ng/mL) 40 50

Vitamin D Levels and Supplementation

25(OH)D 1,25(OH)2D D on Admission (%)

Sufficient 42.5 7.4 25.1 10.3 75

Insufficient 16.2 5 15.6 11.3 42

Deficient 7.1 1.6 10.5 3.4 16

P value <.0001* .0061* .0268*

DX D deficiency

Patient Characteristics

Ages ranged from 24-87

Sufficient 71.3 4.1 50 50 Insufficient 65.6 13.6 40 60 Deficient 55.8 14.7 39 61 1.0000 P value .0187*

Age (years) Race (%) White Black Gender (%) Female

25 75
75 25

46 54
86 14

33 67
63 37 .1480

Dialysis (%) Chronic Temporary



Calcium (mg/dL): mean 8.9 (normal) <8.9 (low)

Sufficient 8 .6
0 4

Insufficient 8.4 1
6 21

Deficient 8.5 .7
7 18

P value .6081



Albumin (g/dL): mean 3.5 (normal) <3.5 (low)

Sufficient 2.1 .6 0 4

Insufficient 2.3 .7 0 27

Deficient 2.4 .7 0 25

P value .6902


PTH (pg/mL): mean <53.5 (normal) 53.5-300 >300

Sufficient 71.5 48 2 2 0

Insufficient 124 86.2 6 19 2

Deficient 139.9 154.7 7 14 2

P value .5635


Other Major Diagnoses

T2DM Hypertension Hyperlipidemia

Sufficient 75 50 0

Insufficient 39 32 39

Deficient 42 23 17

P value .4483 .7018 .1387


Unique population Provides evidence that vitamin D deficiency is highly prevalent in late stage CKD patients

of sample was insufficient Increased risk for fractures Complicates T2DM, hypertension

Unable to be predicted by other characteristics

Comparable Studies

Jean et al, 2008

France Analyzed baseline data of 253 patients prior to hemodialysis 89% prevalence rate

Saab et al, 2007

St. Louis Cohort of 119 subjects Examined prevalence of vitamin D deficiency, then examined supplementation with ergocalciferol 92% prevalence rate

Other Key Findings: Deficiency Diagnosis

No patients were diagnosed with vitamin D deficiency


be due to NKFs recommendations Only 4 patients had PTH above 300 pg/mL Would re-assessing guidelines be beneficial?

Other Key Findings: Age

Vitamin D insufficient group significantly older than deficient group


common in older adults May be due to supplementation 42% of insufficient group was on supplementation, 16% of deficient group was on supplementation

Other Key Findings: Major Diagnoses


of the sample
of the sample



Small sample size Misclassification


diagnosis was not in medical records If patient had disease that was not yet diagnosed

Some subjects had been on supplements while others had not

Suggestions for Future Research

Larger study sample Only include subjects who had not been supplemented Include other associated measures


Prevalence of vitamin D deficiency in kidney damage is extremely high Unable to label people as high risk

regardless of PTH may be beneficial

How do we use this information


for studies on vitamin D supplementation Safety and effectiveness of supplementation