What you need to know about Vitamin A and CKD

For a long time I have known that Vitamin A and kidney disease don’t mix. Standard renal vitamins (replavite and renavite) don’t contain any Vitamin A. But why is Vitamin A so bad? Today, I’m combing through the carrots tops of Vitamin A and CKD.

Review of Vitamin A

Ok, first stop, a quick refresher on Vitamin A. Carrots are high in beta-carotene. Beta-carotene is a water-soluble, pre-formed compound for vitamin A. Vitamin A from supplements, eggs, fish and organ meats is fat soluble and is most frequently in the form of retinol or retinyl esters.

According to the National Institute of Health Vitamin A helps with:

• Immune Function
• Cellular Communication
• Growth and Development
• Reproduction

The duodenum is responsible for vitamin A absorption. From there, stored vitamin A heads to the liver. The most common sign of Vitamin A deficiency is night blindness (Xerophthalmia). Night blindness occurs as the eye’s reserves of vitamin A become depleted. Depletion occurs when the plasma retinol levels are low.

For women of child-bearing age, excess vitamin A is teratogenic. Teratogenic means birth defects. For everyone else, hip fracture and osteoporosis can occur with hypervitaminosis A.

Is blood work good for measuring Vitamin A levels?

Yes and No.

Vitamin A Deficiency: Serum retinol levels only decrease when the other body stores are depleted. This means that blood results will only tell us when a Vitamin A deficiency is moderate to severe. It’s not a good early marker. However, for those who are acutely ill, retinol levels may be inaccurate. Acute events can cause decreases in serum concentrations, which aren’t reflective of vitamin A status.

Vitamin A Toxicity: According to this article, there have been case reports of vitamin A toxicity with normal circulating retinol levels. This suggests serum retinol may not be a good indicator of toxicity. The liver is the primary storage site for Vitamin A. Animal studies have also shown that vitamin A can also be stored outside the liver. For that reason, someone could have normal levels in their blood but still have too much vitamin A in their body.

Vitamin A in CKD

Vitamin A levels in CKD tend to be high. Though interestingly, according to this article, dietary intake of Vitamin A in the CKD population tends to be low.

I happened to also look at this in my PhD. Among the cohort of adults living with diabetes and kidney disease that I studied only 20% of our population met the RDA for Vitamin A. And interestingly, getting a high diet quality score, (we used the healthy eating index and Mediterranean diet score) didn’t increase your chances of meeting the RDA.

Hemodialysis does not remove vitamin A because vitamin A molecules are too big to pass through the dialyzer.

Are high levels of Vitamin A harmful in CKD?

Many CKD patients have high levels of Vitamin A in their blood. But whether are not this is actually harmful is controversial. High levels of plasma vitamin A are though to be related to increased plasma retinol binding protein and may be clinically insignificant. We also don’t know if adults with CKD accumulate high levels of vitamin A in their tissue.

This means that while blood tests for Vitamin A will often report high in the CKD population, we don’t really know if this means they are actually experiencing vitamin A toxicity. In fact, some studies have reported that those with the lowest levels of vitamin A are more likely to experience sudden death than those with higher vitamin A levels. And interestingly, these low levels were still higher than “normal” for the general population.

Should we supplement Vitamin A?

Probably not. Supplemental vitamin A doses above the RDA may cause Vitamin A toxicity. Kidney Guidelines groups recommend avoiding Vitamin A supplementation. Further more, we have no evidence that giving Vitamin A will improve outcomes.

That being said, the authors of this review suggest that for adults with nephrotic syndrome or nondialysis CKD patients, meeting the RDA for Vitamin A appears reasonable.

Vitamin A and Hypercalcemia

Hypercalcemia has been associated with high vitamin A levels. Retinoids have osteolytic actions on bone and are the probable mechanism. For those with hypercalcemia, It is considered prudent to rule out vitamin A toxicity. And for us dietitians, this also likely means that if we are talking with patients about hypercalcemia, we should double check they aren’t getting too much vitamin A.

Take Aways

Do you ever feel like the more your know the less you know? I think my dive into the topic of Vitamin A and CKD has left me with this feeling. Here are my key take aways:

• Vitamin A levels in the blood tend to be high among adults and children with CKD
• We don’t know if high Vitamin A levels are actually harmful. Some studies suggest that lower vitamin A levels (though still above levels seen in the general population) may be associated with sudden death
• Vitamin A intake tends to be low. Though, in most cases, vitamin A supplementation should be avoided. Aim to meet the RDA if possible.
• In cases for hypercalcemia, Vitamin A intake should be evaluated.
• Lab values for vitamin A are difficult to interpret in the general population and even harder to interpret in the CKD population (see my summary table below)

Summary on Interpretation of Serum Retinol Levels