CALCIUM / PHOSPHORUS BALANCE
In renal insufficiency phosphorus is not anyone’s friend. The same phosphorus that has so many helpful roles in the body (from transferring energy in ATP to combining with calcium to form bone), turns against us in a condition called Renal Secondary Hyperparathyroidism.
The short version is that the failing kidney is no longer good at getting rid of excess phosphorus and phosphorus levels in the blood begin to rise. The rise in phosphorus upsets the delicate balance between calcium and phosphorus and activates a regulatory hormonal cascade which attempts to re-establish control. Without healthy kidney tissue to play its role in this balance, the body is fighting a losing battle. Calcium is mobilized from bone to balance the phosphorus but in the end this only serves to demineralize and weaken the bones and cause calcium phosphate deposits to form in soft tissues. These mineral deposits are inflammatory and very damaging.
The hormones that play roles in the regulation of calcium and phosphorus are: parathyroid hormone and calcitriol (which most of us know as Vitamin D).
REVIEW OF PARATHYROID HORMONE AND VITAMIN D
While our discussion of renal disease largely revolves around phosphorus, the importance of calcium cannot be underestimated. Movement of calcium ions is what allows our muscle fibers to contract, not just in our arms and legs but also in our hearts and involuntary intestinal and blood vessel muscles as well. Calcium combined with phosphorus makes up bone; in fact, bone can be considered a storage depot for calcium when we need some in a pinch. The blood level of calcium is tightly regulated by hormones within a narrow range as too much calcium is dangerous as is too little.
Human parathyroid glands are shown here.
Parathyroid hormone activates calcitriol
Both parathyroid hormone and calcitriol drive calcium out of the bones and into the bloodstream thus raising calcium blood levels. In the kidney, both parathyroid hormone and calcitriol reduce calcium excretion (i.e. they make the kidney save calcium and not urinate it away). This further increases blood calcium levels. When it comes to phosphate, though, these two hormones no longer work for the same effect: calcitriol serves to save phosphorus and parathyroid hormone acts to dump it.
Parathyroid hormone causes the kidney to dump phosphorus
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.
But the kidney may not have enough capacity to activate vitamin D no matter how much parathyroid hormone is circulating. This means there is no “off switch” for parathyroid hormone secretion.
More and more parathyroid hormone is desperately 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 body’s 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.
Making matters worse are other effects of excess parathyroid levels. In high amounts, nerves cannot conduct electrical impulses properly. Patients become dazed and poorly responsive.
THE GOAL IS TO KEEP THE PHOSPHORUS LEVEL
IF THIS IS NOT POSSIBLE,
HOW DO WE CONTROL PHOSPHORUS LEVELS?
LOW PHOSPHORUS DIET
We have already reviewed the importance of changing to a prescription renal food early in the course of renal disease. One of the benefits of these diets is that they are low in phosphorus which helps keep blood phosphorus levels under control.
Click here for dietary therapy information.
Often simply giving fluids under the skin at home provides enough extra circulation through the kidneys for the extra phosphorus to be excreted normally. Further treatment may not be needed.
Click here for fluid therapy information.
ORAL PHOSPHATE BINDERS
If diet alone has not controlled phosphate levels after 2-4 weeks, something more aggressive is needed. There are several products available to bind dietary phosphates in the intestinal tract thus preventing them from entering the body. Calcium carbonate and aluminum hydroxide based antacids can be used plus there is a product for humans called Sevelamer hydrochloride (Renalgel®) which is marketed as a human phosphate binder. The problem with using human products such as these is their flavoring which animals frequently find objectionable. Since these pets frequently have appetite issues already we do not want to contribute to the problem by administering unpalatable medicines.
A newer veterinary product called “Epikitin,” a brand of chitosan, has been marketed. Tests show that this powder, which is sprinkled on the food, does not alter palatability of the food. Chitosan is extracted from the shells of shrimp and has been developed for many medical uses. Topically it induces rapid blood clotting. In the intestinal tract it is used to bind fats as well as phosphorus. While its role in weight loss has not panned out, it seems to be effective in binding phosphorus. Most veterinary hospitals are able to order it.
One might think that calctriol would not be helpful in this situation since it leads the kidney to retain phosphorus. The good news is that when small enough doses are given, calcitriol can still act as the “off switch” for parathyroid hormone without causing the kidney to retain phosphorus. The amounts needed for this beneficial effect are so small (they are measured in nanograms) that a compounding pharmacy is needed to custom make the product at the proper dose.
For more details on calcitriol, click here.