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Monday, January 28, 2013

Calcitriol for Use in Cats with Kidney Issues

Calcitriol (Rocaltrol)

Calcitriol is mostly used in the treatment of chronic kidney failure although it can also be used in hypocalcemia (low blood calcium). The relationship between calcitriol (active Vitamin D) and parathyroid hormone is somewhat complicated but it is not possible to understand the function of this medication without some understanding of the system.
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 because vitamin D is actually a hormone. To understand how calcitriol is helpful therapeutically, the following offers some background information 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 digested 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 further modification (a hydroxyl group is added to the 25th carbon of the vitamin D3 molecule) thus forming 25-hydroxycholecalciferol, which is too hard to pronounce and is generally referred to as 25-D3 or calcidiol.
From here, calcidiol circulates to the kidney for its final activation. Another hydroxyl group is added in the final activation to form 1,25 dihydroxycholecalciferol, aka calcitriol.
Actions of Vitamin D and Parathyroid Hormone (PTH)
There are four tiny parathyroid glands around the thyroid gland in the throat area. These glands produce a biochemical called parathyroid hormone, often abbreviated as PTH. When blood calcium drops, PTH is secreted heavily.
Parathyroid hormone encourages the activation of calcidiol into calcitriol by the kidney.
Both PTH and calcitriol act to increase calcium levels by mobilizing calcium from the bones and preventing the kidney from excreting calcium.
PTH may encourage calcitriol activation but calcitriol instructs the parathyroid glands to cut PTH secretion. This means that when there is enough calcitriol, PTH secretion shuts off. This prevents the blood calcium level from increasing out of control.
There is a third hormone called calcitonin that is responsible for excess calcium returning to the bones for storage.

When it comes to phosphorus PTH and calcitriol act as opposites.
Calcitriol acts to have the kidney retain phosphorus while PTH instructs the kidney to dump phosphorus.

These hormones work together to maintain the blood calcium level in a specific range.
What Happens in Kidney Failure?
In early kidney failure, the kidney is not able to activate vitamin D efficiently nor is it able to adequately excrete phosphorus. 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.
But the kidney may not have enough capacity to activate vitamin D no matter how much PTH is circulating. More and more PTH is desperately secreted to get some vitamin D activated and to get the excess phosphorus dumped. 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 body’s soft tissues (which, of course, further lowers blood calcium levels). This removal of calcium from the circulation causes the bones to release all available calcium in an attempt to maintain a normal blood calcium level. 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 or liquid form, the above disaster can hopefully be averted or reversed. (It is more easily averted than reversed.) It has been established that PTH 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 PTH 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 was taken. The animals all received calcitriol. Approximately 80% of the owners reported that their pets were brighter and more social and had better appetites on calcitriol. It was also felt that these animals had a substantially longer life span than patients not receiving calcitriol.
Side Effects
If calcitriol elevates serum calcium levels, this can lead to calcium precipitation in the kidneys, making kidney damage worse. Calcitriol cannot be given to patients with elevated serum calcium levels, and monitoring is necessary to make sure serum calcium levels do not rise.
Interactions with other Drugs
Phosphate binders are common in the treatment of kidney disease. If the binder in use contains calcium, elevated blood calcium levels could become a concern.
Cautions and Concerns
Calcitriol cannot be used in patients that have an elevated (greater than 6 mg/dl) plasma phosphorus level. Calcitriol 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.
It is helpful to monitor PTH levels in patients on calcitriol therapy as some dosage adjustment is sometimes beneficial depending on the PTH level. This kind of monitoring is not crucial to calcitriol use, however.
Calcitriol can be given with or without food.
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 that the diseased kidney cannot activate, and manufactured doses of the prescription product are too high).