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Vitamin D Supplementation in Patients with Renal

Failure

Zachary Siemieniak
Andrews University Dietetic Internship
April 25th, 2018
Introduction
• RD in inpatient setting, without extensive training in renal
nutrition, may find it difficult to provide vitamin D
recommendations to patients experiencing renal failure.
• d/t lack of readily available information regarding the
subjects of supplementation of vitamin D.
• This short-presentation will discuss:
- What vitamin D is
- Function of the kidneys in vitamin D synthesis
- Nutrition therapy to benefit individuals with impaired
kidney function
Role of Vitamin D
• Vitamin D = fat-soluble vitamin naturally present in some foods,
added to others, and available as a dietary supplement.
• Active vitamin D controls balance of Ca+, Phos and PTH
• Vitamin D that the body acquires from sunlight and food is inactive
when renal failure occurs.1
• Vitamin D active and inactive forms: Ergocalciferol (Vitamin D2),
Cholecalciferol (Vitamin D3), Calcidiol (25-hydroxyvitamin D),
Calcifidiol (25-hydroxy-vitamin D metabolite), Calcitriol (1,25
dihydroxy-vitamin D).1

1. Goldsmith DJ. Pro: Should we correct vitamin D deficiency/insufficiency in


chronic kidney disease patients with inactive forms of vitamin D or just treat
them with active vitamin D forms?: Table 1. Nephrology Dialysis
Transplantation. 2016;31(5):698-705. doi:10.1093/ndt/gfw082.
Role of Vitamin D Cont.
• National Kidney Foundation guidelines for bone & mineral
metabolism focus on using vit D to suppress elevated PTH in CKD.1
• With ↓ renal function there is progressive decline in the activity of
1α-hydroxylase, the enzyme that converts 25-hydroxyvitamin D2
to 1,25-dihydroxyvitamin D3 (calcitriol). 1
• Using vitamin D receptor activators (VDRAs) such as calcitriol
(Rocaltrol®), paricalcitol (Zemplar®), or doxercalciferol (Hectorol®)
has been shown to reduce mortality in dialysis and non-dialysis
pts. 1

1. Goldsmith DJ. Pro: Should we correct vitamin D deficiency/insufficiency in


chronic kidney disease patients with inactive forms of vitamin D or just treat
them with active vitamin D forms?: Table 1. Nephrology Dialysis
Transplantation. 2016;31(5):698-705. doi:10.1093/ndt/gfw082.
Role of vit D Cont.
• DRIs developed by the Food and Nutrition Board (FNB) established
a RDA of vit D that is sufficient to maintain bone health and
normal calcium metabolism in healthy people.
• RDAs for vitamin D are listed in IUs and mcg/mL
• Sunlight may be a major source of vit D for some, but the vit D
RDAs are set on the basis of minimal sun exposure.
• The two most common methods to test vitamin D status is using
antibody based and liquid chromatography based tests.1

1. Goldsmith DJ. Pro: Should we correct vitamin D deficiency/insufficiency in


chronic kidney disease patients with inactive forms of vitamin D or just treat
them with active vitamin D forms?: Table 1. Nephrology Dialysis
Transplantation. 2016;31(5):698-705. doi:10.1093/ndt/gfw082.
Vitamin D deficiencies
• Nutrient deficiencies are usually the result of dietary inadequacy,
impaired absorption and use, increased requirement, or increased
excretion.2
• A vitamin D deficiency can occur when usual intake is lower than
recommended levels over time, exposure to sunlight is limited, the
kidneys cannot convert 25(OH)D to its active form, or absorption
of vitamin D from the digestive tract is inadequate. 2
• Rickets (in children) and osteomalacia (adults). The fortification of
milk with vitamin D beginning in the 1930s has made rickets a rare
disease in the US.

2. Jean G, Souberbielle JC, Chazot C. Vitamin D in Chronic Kidney Disease and


Dialysis Patients. Nutrients. 2017;9(4):328. doi:10.3390/nu9040328.
Vitamin D deficiencies cont.
• Much of the US lies above the 40° north latitude. Research
indicates that ppl residing in this area have insufficient duration
and intensity of sun exposure for optimal synthesis of vitamin D. 2
Unless vitamin D is obtained from fortified foods or from
supplements, many North Americans are at risk of deficiency.
• Physical findings of vitamin D deficiency include:
- persistently open anterior fontanel (after age 18 months),
craniotabes (softening of skull across back and sides before age 1
year)
- epiphyseal enlargement (painless) at wrist, knees and ankles
- pigeon chest and Harrison's sulcus (horizontal depression on lower
chest border)

2. Jean G, Souberbielle JC, Chazot C. Vitamin D in Chronic Kidney Disease and


Dialysis Patients. Nutrients. 2017;9(4):328. doi:10.3390/nu9040328.
Ways to Detect Vitamin D Deficiency
• Vitamin D adequacy is best determined by measurement of the 25-
hydroxyvitamin D concentration in the blood. A level of 20-50 ng/mL is
considered adequate for healthy people.3 A level less than 12 ng/mL
indicates vitamin D deficiency. 3
• 25-hydroxyvitamin D is the major form found in the blood and is the
relatively inactive precursor to the active hormone, 1,25-
dihydroxyvitamin D. 3 Because of its long half-life and higher
concentration, 25-hydroxyvitamin D is commonly measured to assess
and monitor vitamin D status in individuals. 3
• A low level of 1,25-dihydroxyvitamin D can be seen in kidney disease
and is one of the earliest changes to occur in persons with early kidney
failure. 3 A high level of 1,25-dihydroxyvitamin D may occur when there
is excess parathyroid hormone or when there are diseases that can
make 1,25-dihydroxyvitamin D outside of the kidneys. 3

3. Patel T, Singh AK. Role of Vitamin D in Chronic Kidney Disease. Seminars in


nephrology. 2014;29(2):113-121. doi:10.1016/j.semnephrol.2009.01.004.
Prevalence of Vitamin D Deficiency
• Vitamin D insufficiency affects almost 50% of the population
worldwide. An estimated 1 billion people worldwide, across all
ethnicities and age groups, have a vitamin D deficiency.4 This
pandemic of hypovitaminosis D can mainly be attributed to
lifestyle and environmental factors.
• Vitamin D levels in humans depend on two sources: (1) exposure
to the ultraviolet rays of the sun for conversion of 7-
dehydrocholesterol in the skin to vitamin D3 (cholecalciferol) and
(2) dietary intake of either vitamin D2 (ergocalciferol) or vitamin
D3.4 Vitamin D2 and vitamin D3 must be metabolically activated in
the liver and kidney before becoming fully active on target tissues.

4. Xu A, Feng M, Lv J, et al. Predictors of Vitamin D deficiency in predialysis


patients with stage 3–5 chronic kidney diseases in Southern China. Nigerian
Journal of Clinical Practice. 2017;20(10):1309. doi:10.4103/njcp.njcp_27_17.
Ways to Improve Absorption of Vitamin D
• Ways to improve vitamin D absorption and utilization.
1. Consume Enough Healthy Fats- Vitamin D is a fat soluble vitamin, meaning it is
absorbed in lipids and stored in the body tissues for use.4 Cholesterol is also a
precursor to vitamin D, and must be consumed in adequate amounts for its
synthesis to occur properly.4
2. Maintain Healthy Gut Flora- Dietary vitamin D is absorbed in the jejunum and
ileum of the SI, and is dependent on sufficient quantities of bile salts.4 Poor gastric
health and food allergies can cause a binding of vitamin D in the small intestine
rendering it unusable. Maintaining healthy gut flora by eating fermented foods
and taking a probiotic regularly are helpful measures to promote the absorption of
nutrients.
3. Supplement with Magnesium- Magnesium is a crucial cofactor for the enzymes
that convert vitamin D to its hormonally active form, calcitriol.4 When vitamin D is
consumed in an individual who is low in magnesium, it cannot be properly used by
the cells. Supplementing with 400-900 mg with increasing vitamin D is crucial to
successfully balancing deficiencies.4

4. Xu A, Feng M, Lv J, et al. Predictors of Vitamin D deficiency in predialysis patients with


stage 3–5 chronic kidney diseases in Southern China. Nigerian Journal of Clinical Practice.
2017;20(10):1309. doi:10.4103/njcp.njcp_27_17.
Sources of Vitamin D
• Few foods in nature contain vitamin D. Fatty fish (salmon, tuna, and
mackerel) and fish liver oils are among the best sources.5 Small amounts of
vitamin D are found in beef liver, cheese, and egg yolks. Vitamin D in these
foods is primarily in the form of vitamin D3. 5 Some mushrooms also provide
vitamin D2 in variable amounts when exposed to UV light.
• Fortified foods provide most of the vitamin D in the American diet. In the
1930s, milk fortification was implemented. 5 Other dairy products made
from milk, such as cheese and ice cream, are generally not fortified.
• Ready-to-eat breakfast cereals often contain added vitamin D, as do some
brands of orange juice, yogurt, margarine and other food products. Both
the US and Canada mandate the fortification of infant formula with vitamin
D: 40–100 IU/100 kcal in the US and 40–80 IU/100 kcal in Canada. 5

5. Kennel KA, Drake MT, Hurley DL. Vitamin D Deficiency in Adults: When to Test and
How to Treat. Mayo Clinic Proceedings. 2013;85(8):752-758.
doi:10.4065/mcp.2010.0138.
Toxicity of Vitamin D
• High levels of vitamin D & Ca+ can lead to the calcification and
damage to organs, particularly the kidneys and blood vessels. If
magnesium levels are low, they can cause a low Ca+ level that is
resistant to vitamin D and PTH regulation.6 It may be necessary to
supplement both magnesium and calcium to regain normal function.
• Vitamin D toxicity can cause non-specific symptoms such as anorexia,
weight loss, polyuria, and heart arrhythmias.6 More seriously, it can
also raise blood levels of calcium which leads to vascular and tissue
calcification, with subsequent damage to the heart, blood vessels,
and kidneys. 6

6. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, Treatment, and
Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice
Guideline. The Journal of Clinical Endocrinology & Metabolism.
2013;96(7):1911-1930. doi:10.1210/jc.2011-0385.
Toxicity of Vitamin D cont.
• Excessive sun exposure does not result in vitamin D toxicity 6
• Intakes of vitamin D from food that are high enough to cause toxicity
are very unlikely. Toxicity is much more likely to occur from high
intakes of dietary supplements containing vitamin D.
• Long-term intakes above the UL increase the risk of adverse health
effects. Most reports suggest a toxicity threshold for vitamin D of
10,000 to 40,000 IU/day.6
• Vitamin D₃ at 10,000 IU/d for 12 weeks, is a safe, effective, and well
tolerated strategy for clinical vitamin D₃ repletion in people with
suboptimal 25(OH)D.6 Other researchers suggest supplementing
vitamin D2 at 50,000 units/week for acute repletion. 6

6. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation,


Treatment, and Prevention of Vitamin D Deficiency: an Endocrine
Society Clinical Practice Guideline. The Journal of Clinical Endocrinology
& Metabolism. 2013;96(7):1911-1930. doi:10.1210/jc.2011-0385.
Physiological Processes of Vitamin D Production
• Vitamin D is produced by skin exposed to UV B radiation or obtained
from dietary sources and supplements. Vitamin D comes from two
sources: endogenous, which is produced in the skin on exposure to
sunlight, and exogenous, which is ingested in foods and
supplements.7
• Vitamin D2 (ergocalciferol, which comes from plants) is found in
fortified foods and in most vitamins and supplements. Vitamin D3
(cholecalciferol, which comes from animals) is the form produced in
the body and is also used in some supplements. Vitamin D2 and D3
are equally effective when they are converted by the liver and the
kidney into the active form, 1,25-dihydroxyvitamin D. 7
• Most meet at least some of their vitamin D needs through exposure
to sunlight. Individuals with limited sun exposure need to include
vitamin D in their diet or take a supplement.

7. Nair R, Maseeh A. Vitamin D: The “sunshine” vitamin. Journal of


Pharmacology & Pharmacotherapeutics. 2013;3(2):118-126.
doi:10.4103/0976-500X.95506.
Dietary supplements
• In supplements & fortified foods, vitamin D is available in two
forms, D2 (ergocalciferol) and D3 (cholecalciferol). The two forms
have traditionally been regarded as equivalent based on their
ability to cure rickets.
• Most steps involved in the metabolism and actions of vitamin D2
and vitamin D3 are identical.7 Both forms (as well as vitamin D in
foods and from cutaneous synthesis) effectively raise serum
25(OH)D levels. 7

7. Nair R, Maseeh A. Vitamin D: The “sunshine” vitamin. Journal of


Pharmacology & Pharmacotherapeutics. 2013;3(2):118-126.
doi:10.4103/0976-500X.95506.
Medications
• Zemplar, Hectoral, and Calcitriol are vitamin D analogs dosed by the RD to
decrease PTH. The RD monitors Ca+ because it can become elevated due to
the use of some phos binders. Vitamin D should be supplemented
individually to suppress hyperparathyroidism.
• Zemplar is an active form of vitamin D used to prevent and treat secondary
hyperparathyroidism in patients with Stage 3/4 CKD and in Stage 5 pts on
dialysis.8 When kidney function declines, it can lead to a silent condition (no
s/s) called secondary hyperparathyroidism (SHPT). SHPT is very common in
people in Stages 4/5 of CKD and can cause parathyroid glands to become
permanently enlarged.
• ZEMPLAR works by telling the parathyroid glands to stop producing too
much PTH. 8 Initial dosages are 0.04-0.1 mcg/kg IV 3 x/week, no more
frequently than every other day. 8

8. Hadjiyannakos D, Filiopoulos V, Trompouki S, et al. Treatment with oral paricalcitol in


daily clinical practice for patients with chronic kidney disease stage 3-4: a preliminary study.
Clinical Kidney Journal. 2013;6(2):164-168. doi:10.1093/ckj/sfs188.
Medications cont.
• Doxercalciferol, the active ingredient in Hectorol®, is a synthetic
vitamin D2 analog that undergoes metabolic activation in vivo to
form 1α,25-dihydroxyvitamin D2, a naturally occurring, biologically
active form of vitamin D2.9
• Don’t combine Magnesium-containing antacids and Hectorol d/t
potential hypermagnesemia. 9 Dosing based on iPTH levels with
monitoring of serum calcium & phos levels.
• The recommended initial dose of Hectorol is 4 mcg administered
intravenously as a bolus dose three times weekly at the end of
dialysis. 9

9. Melamed ML, Thadhani RI. Vitamin D Therapy in Chronic Kidney Disease and
End Stage Renal Disease. Clinical Journal of the American Society of
Nephrology : CJASN. 2015;7(2):358-365. doi:10.2215/CJN.04040411.
Vegetarian Implications
• Vegetarianism and CKD have been thought to be impossible to
combine. Plant-based diets, despite containing low amounts of
protein, are also rich in potassium and phosphorus, and therefore
they are believed to be unsuitable for CKD patients. 10
• The National Kidney Foundation recommends vegetarianism, or a
part-time vegetarian diet as being beneficial to CKD patients.
• Benefits of being on a vegetarian diet with CKD are numerous.
Plant protein sources have been shown to:
-Decrease protein in the urine (proteinuria),
-slow the decline of glomerular filtration rate (GFR) and
-slow kidney blood flow resulting in less kidney tissue damage when
compared to animal proteins. 10

10. Gluba-Brzózka A, Franczyk B, Rysz J. Vegetarian Diet in Chronic


Kidney Disease—A Friend or Foe. Nutrients. 2017;9(4):374.
doi:10.3390/nu9040374.
Vegetarian Implications cont.
• A well-planned vegetarian diet is associated with cardiovascular
benefits and the correction of CKD complications. 10
• Its benefits are associated with the large amounts of dietary fibers,
folic acid, K+, Mg, vitamin E & C and carotenoids, as well as the many
phytochemicals contained. 10
• Pts who decide to switch to a vegetarian diet may also adopt other
good lifestyle practices, including higher levels of physical activity,
refraining from smoking, and decreased consumption of alcohol.
• Vegetarian diets may help slow down the progression of kidney
disease without compromising nutritional needs. The renal vitamin
that is prescribed for hemodialysis patients should contain vitamin
B12 and D, iron and zinc. All dialysis patients are regularly evaluated
and prescribed calcium, vitamin D and intravenous (IV) iron by their
doctors if and when they need it. 10

10. Gluba-Brzózka A, Franczyk B, Rysz J. Vegetarian Diet in Chronic


Kidney Disease—A Friend or Foe. Nutrients. 2017;9(4):374.
doi:10.3390/nu9040374.
Conclusion
To summarize, vitamin D insufficiency affects almost 50% of the
population worldwide. Vitamin D is a fat-soluble vitamin that is
naturally present in very few foods, added to others, and
available as a dietary supplement. Vitamin D that the body
naturally gets from sunlight and food is inactive when renal
failure occurs. Therefore, dietary supplementation at
pharmacological levels as well as medications are available to
prevent complications related to vitamin D deficiency in CKD
patients. Vegetarian diets are suitable for CKD patients with
positive outcomes such as decreased proteinuria, slower decline
of GFR and kidney blood flow and result in less kidney tissue
damage when compared to animal foods.
References
1. Goldsmith DJ. Pro: Should we correct vitamin D deficiency/insufficiency in chronic kidney
disease patients with inactive forms of vitamin D or just treat them with active vitamin D
forms?: Table 1. Nephrology Dialysis Transplantation. 2016;31(5):698-705.
doi:10.1093/ndt/gfw082.
2. Jean G, Souberbielle JC, Chazot C. Vitamin D in Chronic Kidney Disease and Dialysis Patients.
Nutrients. 2017;9(4):328. doi:10.3390/nu9040328.
3. Patel T, Singh AK. Role of Vitamin D in Chronic Kidney Disease. Seminars in nephrology.
2014;29(2):113-121. doi:10.1016/j.semnephrol.2009.01.004.
4. Xu A, Feng M, Lv J, et al. Predictors of Vitamin D deficiency in predialysis patients with stage
3–5 chronic kidney diseases in Southern China. Nigerian Journal of Clinical Practice.
2017;20(10):1309. doi:10.4103/njcp.njcp_27_17.
5. Kennel KA, Drake MT, Hurley DL. Vitamin D Deficiency in Adults: When to Test and How to
Treat. Mayo Clinic Proceedings. 2013;85(8):752-758. doi:10.4065/mcp.2010.0138.
6. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, Treatment, and Prevention of
Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline. The Journal of Clinical
Endocrinology & Metabolism. 2013;96(7):1911-1930. doi:10.1210/jc.2011-0385.
7. Nair R, Maseeh A. Vitamin D: The “sunshine” vitamin. Journal of Pharmacology &
Pharmacotherapeutics. 2013;3(2):118-126. doi:10.4103/0976-500X.95506.
8. Hadjiyannakos D, Filiopoulos V, Trompouki S, et al. Treatment with oral paricalcitol in daily
clinical practice for patients with chronic kidney disease stage 3-4: a preliminary study. Clinical
Kidney Journal. 2013;6(2):164-168. doi:10.1093/ckj/sfs188.
9. Melamed ML, Thadhani RI. Vitamin D Therapy in Chronic Kidney Disease and End Stage Renal
Disease. Clinical Journal of the American Society of Nephrology : CJASN. 2015;7(2):358-365.
doi:10.2215/CJN.04040411.
10. Gluba-Brzózka A, Franczyk B, Rysz J. Vegetarian Diet in Chronic Kidney Disease—A Friend or
Foe. Nutrients. 2017;9(4):374. doi:10.3390/nu9040374.