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BRAND NAME: ROCALTROL
Calcitriol and 1,25 dihydroxycholecalciferol are both scientific names for active vitamin D. The biochemistry of vitamin D is very different from that of other vitamins; vitamin D is actually a hormone. To understand how calcitriol is helpful in the treatment of chronic renal failure, it is helpful to understand some background infromation about vitamin D, its metabolic opposite Parathyroid hormone, and the general calcium and phosphorus balance within the body.
A REVIEW OF VITAMIN D
The story of vitamin D begins when a vitamin D precursor is eaten. The precursor we get from plants is called ergosterol and the precursor we get from eating animal tissues is called 7-dehydrocholesterol. These substances are absorbed into the body when they are eaten and transported to the skin for modification by sunlight radiation (hence the popular terminology of vitamin D as the sunshine vitamin). The animal origin substance is converted to what is called vitamin D3 or cholecalciferol while the plant substance becomes vitamin D2 or ergocalciferol. From here we will follow the animal origin hormone as it is the most metabolically active.
The next stop is the liver for modification (a hydroxyl group is added to the 25th carbon of the vitamin D3 molecule) thus forming 25-hydroxycholecalciferol. After this, 25-hydroxycholecalciferol (often abbreviated 25-D3 or calcidiol) circulates to the kidney for its final activation. Another hydroxyl group is added in the final activation to form 1,25 dihydroxylcholecalciferol, aka calcitriol.
ACTIONS OF VITAMIN D
Calcitriol has several important actions. It enhances absorption of both calcium and phosphate from the GI tract, promotes release of calcium and phosphate from the bones where they are stored, and causes the kidney not to excrete calcium and phosphate. In short, vitamin D is designed to increase the amount of calcium and phosphorus circulating in the bloodstream.
Calcitriol = Active Vitamin D and causes increased
calcium and phosphorus in the bloodstream.
REVIEW OF PARATHYROID HORMONE
There are four tiny parathyroid glands around the thyroid gland in the throat area. These glands produce a biochemical called parathyroid hormone often abbreviated PTH. When blood calcium drops, parathyroid hormone is secreted heavily. Parathyroid hormones encourages the activation of calcidiol into calcitriol by the kidney. More active vitamin D helps drive the blood calcium level up. Active vitamin D is able to shut off the secretion of parathyroid hormone so that this cascade does not get out of hand.
Parathyroid hormone is able to drive stored calicum and phosphorus from the bones as is vitamin D so these hormones are able to work in concert here but in the kidney they have different functions. In the kidney, while vitamin D saves both calcium and phosphate, parathyroid hormone causes only calcium to be saved and phophate to be dumped. There is a third hormone called calcitonin that keeps the blood calcium level from indefinitely rising. When blood calcium starts to get too high, calcitonin is released to begin storing calcium and phosphate back in the bones until it is needed again.
Parathyroid hormone causes increased calcium and active vitamin D
but reduced phosphorus in the bloodstream.
Calcitonin causes reduced calcium and phosphorus in the bloodstream.
WHAT HAPPENS IN KIDNEY FAILURE?
In early kidney failure, the kidney is not able to activate vitamin D. Not only that but it becomes inefficient at excreting phosphate. As a result active vitamin D levels drop (which results in a drop in blood calcium) and blood phosphate levels start to climb. The calcium drop is seen by the parathyroid gland, PTH is released, and hopefully the situation can be normalized.Â
But the kidney may not have enough capacity to activate vitamin D no matter how much parathyroid hormone is circulating. More and more parathyroid hormone is desparately secreted to get some vitamin D activated and to get the excess phosphorus dumped. But the kidney simply cannot respond. Soon there is so much circulating phosphate that it begins to combine with the blood calcium and calcium phosphate crystals begin to form in the bodyâs soft tissues. This removal of calcium from the circulation causes the bones to release all available calcium, possibly to a point where there is no calcium left to release. The bones becomes soft and bendable (this is classically most notable in the jaws leading to the condition in advanced kidney failure called rubber jaw.) The bone crystals in the soft tissues generate an inflammatory response. None of the tissues involved can function normally. A metabolic disaster has occurred.
HOW THIS MEDICATION IS USED
By giving active vitamin D in pill form, the above disaster can hopefully be averted or reversed. (It is more easily averted than reversed). It has been established that parathyroid hormone is an important toxin in kidney failure and we want to reduce its secretion. This is best done with minute (measured in units 1000 times smaller than the usual dosages) quantities of vitamin D. These quantities are enough to shut off parathyroid hormone secretion but are not high enough to lead to elevated phosphorus levels.
If calcitriol is started early in kidney failure, parathyroid levels may be kept low enough that calcium/phosphorus imbalance never becomes an issue. If it is started later in failure, it is helpful but may not be able to provide as good a response.
Recently a survey of the owners and veterinarians of nearly 2000 pets in chronic renal failure has been formulated. These animals all received calcitriol. Approximately 80% of the owners reported that their pets were brighter and more social and had better appetites on calictriol. It was also felt that these animals had a substantially longer life span than patients not receiving calcitriol.
SIDE EFFECTS
Calcitriol is able to elevate serum calcium in some cases which can further destabilize the calcium phosphorus balance and can create further toxicity issues to the kidney. Calicum is one of the parameters monitored in kidney failure patients. If calcium should elevate, calcitriol is discontinued for a week or so and calcium is rechecked. Due to the complex nature of the above hormone interactions, inadequate calcitriol can also cause calcium elevation. Your veterinarian can direct you further in this instance to determine a more appropriate calcitriol dose.
INTERACTIONS WITH OTHER DRUGS
Phosphate binders are common in the treatment of kidney disease. If the binder in use contains calcium (in veterinary medicine we usually use aluminum containing phosphate binders) elevated blood calcium levels could become a concern.Â
CAUTIONS AND CONCERNS
* Calictriol cannot be used in patients that have an elevated (greater than 6 mg/dl) plasma phosphorus level. Calicitriol might elevate phosphorus further at this stage which is exactly what we do not want. In such patients, plasma phosphorus must be reduced by diet, fluid administration or by phosphate binders before calcitriol can be started.
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* It is helpful to monitor parathyroid hormone levels in patients on calcitriol therapy as some dosage adjustment is sometimes beneficial depending on the parathyroid hormone level. This kind of monitoring is not crucial to calcitriol use, however.
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* Calcitriol can be given with or without food.
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* Special compounding pharmacies are needed to create an oral liquid or capsule in a size beneficial to the individual patient. A commercial vitamin D supplement is not useful (most over the counter formulas include ergocalciferol which the diseased kidney cannot activate and manufactured doses of the prescription product are too high).
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