Kidney disease (KD) is associated with changes in bone health and mineral balance. Vitamin D is a fat-soluble vitamin that is essential for life and is crucial for calcium balance and bone health. The kidneys are central in the activation of vitamin D and play a key role in regulating circulating levels. In this blog, we will discuss the relationship between vitamin D and kidney health.
Vitamin D as a hormone
Vitamin D is a term used to describe a family of compounds derived from cholesterol. There are two major forms to keep in mind. Vitamin D2, or ergocalciferol, is mostly found in plants, and D3, or cholecalciferol, the form found in animal sources and produced naturally in our skin when we’re exposed to the sun. It is a “conditionally essential vitamin” because we need cholesterol precursors to produce it, but we can also consume it with food.
Vitamin D is not only a vitamin, but it’s also considered a hormone because of its direct interaction with cell receptors in the body. We rely on our “factory” in the skin to make Vitamin D when we are exposed to the sun. The UV rays stimulate the conversion of precursors derived from cholesterol into active vitamin D3. Like other hormones derived from cholesterol, such as estrogen and testosterone, not eating or producing enough cholesterol can contribute to a deficiency of vitamin D.
Foods that contain vitamin D
We typically think of vitamin D as “the sunshine vitamin.” However, various factors impact the ability of the body to produce adequate active vitamin D3, including average daily sun exposure, geographic location, skin color, and genetic variations that impact “the vitamin D factory.” Luckily, there are other options for meeting our needs, including consuming vitamin D-rich foods as well as taking a high-quality supplement.
Foods that naturally contain the active form of vitamin D3 include wild salmon, herring, sardines, cod liver oil, tuna, oysters, shrimp, and egg yolks. Surprisingly, mushrooms are the only plant-based source of natural vitamin D2. However, you can actually significantly increase the naturally occurring amount of D3 by laying mushrooms in the sun (learn more here). Since Vitamin D is a fat-soluble vitamin, absorption is best when eaten with a healthy fat or food naturally containing fat.
Many people associate milk with food sources of Vitamin D. However, milk is not naturally a good source of vitamin D. Beverage companies fortify milk and other drinks (like orange juice and nut milk products) and market them as “great sources of vitamin D” – in other words, vitamin D is artificially added in during the manufacturing process.
Vitamin D receptors
Vitamin D is most commonly associated with bone health because it’s necessary for the bone formation process, along with vitamins K, calcium, magnesium, and phosphorous. However, it’s vital beyond bone health. Receptors for vitamin D have been identified in almost all organs in the body. These genes are responsible for the calcium and phosphate balance, immune response, and cell growth and differentiation. The presence of vitamin D receptors in the blood vessels also indicates that vitamin D plays an important role in maintaining heart health.
Activation of Vitamin D by the kidneys (and the liver)
Vitamin D that is produced by our skin or consumed is transported to the liver as a “prohormone” by a protein called Vitamin D Binding Protein (DBP). In the liver, this precursory form is converted by an enzyme called 25-hydroxylase (or CYP2R1). The end-product is called 25-hydroxyvitamin D, abbreviated 25-(OH)D, and is the main circulating form of vitamin D.
Once produced, 25-(OH)D is eventually transported to the kidneys, where another (-OH) group is added. The result is the active hormone called 1,25-Dihydroxyvitamin D (or 1,25-Dihydroxycalceferol, abbreviated 1,25-(OH)2D).
Vitamin D receptors are mainly activated by 1,25 (OH)2D. However, some cells may have a modest capacity to activate vitamin D locally. In addition, at a very high concentration, the less active 25 (OH)D can bind with vitamin D receptors,
Genetic variations in the activating enzymes involved in this multi-step process are well documented and influence the individual ability to activate the prohormone into the needed active product. This is why checking both the 25-(OH)D and the 1,25 (OH)2D levels may give us a better idea of the true level of bioavailable vitamin D.
Vitamin D in Kidney Disease
In KD, the gradual loss of functional kidney tissue responsible for the activation of vitamin D contributes to the deficiency of the active form 1,25 (OH)2D. Interestingly, more than 80% of KD patients also have a low level of the precursor form 25(OH)D when measured in the serum. Several factors have been implicated in the cause of this deficiency, including inadequate outdoor physical activity, inadequate dietary intake, genetic variations, and impaired retention of the filtered 25(OH)D by the kidneys. There is also evidence that the accumulation of waste products, a common effect of KD, can decrease the production of 25(OH)D by the liver.
Remember, vitamin D circulates in the blood bound to DBP. Without this protein to provide transportation, vitamin D precursors will not reach the liver for the step of activation to 25(OH)D. Since some KD causes urinary protein loss, low levels of DBP may contribute to low 25(OH)D in kidney patients. However, there’s conflicting evidence of the significance of this factor. There may be more to the story worth continued research, especially surrounding the genetic variations in the gene that codes for DBP and its subsequent effect on production and binding capacity.
We can’t talk about vitamin D and KD without talking about the parathyroid gland (not to be confused with the thyroid gland). The main function of the parathyroid gland is to maintain blood levels of circulating calcium, a mineral very important in heart and bone health, as well as normal muscle function.
As kidney function declines, phosphate accumulation indirectly contributes to a further reduction in vitamin D activation. These compounding factors promote the production of parathyroid hormone (PTH) by the parathyroid gland. KD). PTH maintains calcium by influencing absorption from the gut as well as increasing its reabsorption during kidney filtration.
When calcium levels in the blood drop too low and endanger cardiac function, it triggers PTH also to mobilize calcium from the bone storage into the blood to normalize circulating levels. This is the contributing mechanism that leads to a high bone turnover, weakened bones, and increased risk of fracture in kidney patients. In addition, vitamin D deficiency in kidney patients has been associated with muscle weakness, falls, insulin resistance, enlargement of heart muscles, blood vessel disease, and calcifications.
The target level of vitamin D in kidney disease patients
There is controversy surrounding the ideal target goal of 25 (OH)D and 1,25(OH2)D for kidney patients. Studies showed that the maximum benefit to decrease muscle weakness and fall risk in kidney patients is in the range between 24-44 ng/mL and that levels less than 15 ng/mL have been associated with increased risk for mortality and progression to dialysis in kidney patients. Conventionally, a target level of ~40 ng/mL but has been the standard of care. However, some practitioners argue that some patients may benefit from higher circulating levels.
Conventional and Integrative Approach to bone health in kidney disease
The conventional medicine approach to bone health in KD has been focused on correcting 1,25(OH)2D levels and decreasing PTH levels (though target levels in KD are unclear). Utilizing active vitamin D analogs has been linked to improved outcomes in KD and dialysis patients.
When addressing vitamin D’s impact on KD risk, we need to pay close attention to dietary factors that impact nutrient status (including calcium, magnesium, vitamin K, and other relevant nutrients), as well as digestive issues that may reduce nutrient absorption from food. In addition, the role of genetic and epigenetic modifications in coding for factors that impact vitamin D activation and vitamin D receptors might mean that simple recommendations to “get more sun” or supplement may not be adequate for some individuals and warrant a more personalized approach to optimize kidney health.
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