Briefly describe a specific question, or set of related questions, about a health care test or treatment that this program should consider.

We are interested in the comparative effectiveness of Vitamin D supplementation in the prevention of chronic kidney disease (CKD). All forms of Vitamin D supplementation could be examined, and compared, including calcitriol (activated), and Vitamins D2 and D3 (ergo- and cholecalciferol). Whether vitamin D insufficiency or deficiency is associated with/causal of CKD still needs to be established. Thereafter, optimal levels of Vitamin D in terms of CKD prevention could be examined. The effectiveness of the various forms of supplementation could be compared.

• What is the optimal level of Vitamin D to prevent CKD in the general population? Is the optimal level impacted by at-risk state (ie. persons with hypertension or, diabetes)?
• What is the comparative effectiveness of strategies to normalize Vitamin D levels among deficient or insufficient patients in preventing CKD?
• What is the comparative effectiveness of different forms of Vitamin D supplementation in preventing CKD?

Does your question include a comparison of different health care approaches? (If no, your topic will still be considered.)

yes

If yes, explain the specific technologies, devices, drugs, or interventions you would like to see compared:

All forms of Vitamin D supplementation could be examined and compared, including calcitriol (activated), and Vitamins D2 and D3 (ergo- and cholecalciferol).

What patients or group(s) of patients does your question apply to? (Please include specific details such as age range, gender, coexisting diagnoses, and indications for therapy.)

The question applies to all CKD patients.

Are there subgroups of patients that your question might apply to? (For example, an ethnic group, stage or severity of a disease.)

We are especially interested in subgroups with high rates of CKD, such as African-Americans and older adults.

Describe the health-related benefits you are interested in. (For example, improvements in patient symptoms or problems from treatment or diagnosis.)

We are primarily interested in the prevention of CKD. Secondarily we are interested in vitamin D mediation of the progression of CKD, and also in mediating complications associated with CKD.

Describe any health-related risks, side effects, or harms that you are concerned about.

Side-effects reported for excess vitamin D:

• Excessive thirst
• Metal taste in mouth
• Poor appetite
• Weight loss
• Bone pain
• Tiredness
• Sore eyes
• Itchy skin
• Vomiting
• Diarrhea
• Constipation
• A frequent need to urinate
• Muscle problems

People with the following conditions may be more sensitive to excess vitamin D:

• High blood calcium or phosphorus levels
• Heart problems
• Kidney disease

Vitamin D may interfere with action of:

• Atorvastatin (Lipitor)
• Calcium channel blockers
• Nifedipine (Procardia)
• Verapamil (Calan)
• Nicardipine (Cardene)
• DiltiaZem (Cardizem, Dilacor)
• Amlodipine (Norvasc)

Digoxin (Lanoxin) - Vitamin D improves absorption of calcium, which can increase the likelihood of a toxic reaction from digoxin.

These drugs may raise the amount of vitamin D in the blood:

• Estrogen -- Hormone replacement therapy with estrogen appears to raise vitamin D levels in the blood, which may have a positive effect on calcium and bone strength. In addition, taking vitamin D supplements along with estrogen replacement therapy (ERT) increases bone mass more than ERT alone. However, this benefit may be lost with the addition of progesterone.
• Isoniazid (INH) -- a medication used to treat tuberculosis.
• Thiazide -- This kind of diuretic (water pill) can increase vitamin D activity and can lead to high calcium levels in the blood.

Vitamin D levels may be decreased by the following medications:

• Antacids -- Taking certain antacids for long periods of time may alter the levels, metabolism, and availability of vitamin D.
• Anti-seizure medications -- these medications include:
• Phenobarbital
• Phenytoin (Dilantin)
• Primidone (Mysoline)
• Valproic acid (Depakote)
• Bile acid sequestrants -- used to lower cholesterol. These medications include
• Cholestyramine (Questran, Prevalite)
• Cholestipol (Colestid)
• Rifampin -- used to treat tuberculosis
• Mineral oil -- Mineral oil also

Appropriateness for EHC Program

Does your question include a health care drug, intervention, device, or technology available (or likely to be available) in the U.S.?

yes

Which priority area(s) and population(s) does this topic apply to? (check all that apply)

EHC Priority Conditions (updated in 2008)

• Cardiovascular disease, including stroke and hypertension
• Diabetes mellitus
• Obesity

AHRQ Priority Populations

• Minority groups
• Elderly
• Individuals with special health care needs, including individuals with disabilities or who need chronic care or end-of-life health care

Federal Health Care Program

• Medicaid
• Medicare

Importance

Describe why this topic is important.

Vitamin D deficiency has been found to be present among 42% of U.S. adults. The rate is higher among CKD patients, with 71% insufficient in stage 3, and 83% in stage 4 CKD. Vitamin D insufficiency is more prevalent among black CKD patients than among white patients, and this may contribute to higher burden of disease among blacks. Vitamin D deficiency is associated with hyperparathyroidism and low bone mineral density in CKD patients. The cost impact is potentially large; $36 -$85 billion could be saved annually by prevention or significant delay of hyperparathyroidism secondary to CKD. Hip, pelvic, or vertebral fracture costs Medicare >$21,700/event, versus vitamin D or analog costs of $168-$14,500/pt./yr. Fractures cost Medicare >$69 million annually in ESRD patients.

What specifically motivated you to ask this question? (For example, you are developing a clinical guideline, working with a policy with large uncertainty about the appropriate approach, costly intervention, new research you have read, items in the media you may have seen, a clinical practice dilemma you know of, etc.)

This topic was identified in our AHRQ/EHC sponsored topic identification project. Among a large number of CKD topics, a group of stakeholders ranked this as a high priority topic.

Does your question represent uncertainty for clinicians and/or policy-makers? (For example, variations in clinical care, controversy in what constitutes appropriate clinical care, or a policy decision.)

yes

If yes, please explain:

It is uncertain as to whether vitamin D supplementation can lead to CKD prevention. There is uncertainty in how to handle vitamin D supplementation. Optimum dosage, form, and monitoring are necessary to prevent hyperparathyroidism and fractures while avoiding hypercalcemia and cardiovascular problems. There is also uncertainty regarding which outcome measures are important for monitoring and assessing effectiveness. Resolving these uncertainties is important.

Potential Impact

How will an answer to your research question be used or help inform decisions for you or your group?

Answers to the above questions would help inform guidelines for optimizing vitamin D intake and prevention of CKD in the general population, as well as guidelines for optimizing vitamin D supplementation for CKD patients to prevent or slow progression of CKD.

Describe the timeframe in which an answer to your question is needed.

We would like to see this in a Topic Development & Triage project very soon.

Describe any health disparities, inequities, or impact on vulnerable populations your question applies to.

Vitamin D Insufficiency is more prevalent among black CKD patients than among white patients, and this may contribute to higher burden of disease among blacks. The relationship of skin color, vitamin D production, metabolism and CKD incidence is not well understood.

Nominator Information

Other Information About You: (optional)

Please choose a description that best describes your role or perspective: (you may select more than one category if appropriate)

Answers to the above questions would help inform guidelines for optimizing vitamin D intake and prevention of CKD in the general population, as well as guidelines for optimizing vitamin D supplementation for CKD patients to prevent or slow progression of CKD.

Are you making a suggestion as an individual or on behalf of an organization?

Organization

Please tell us how you heard about the Effective Health Care Program

We are an AHRQ/EHC EPC