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). The story co-stars a substance called "Fibroblast Growth Factor 23". These three materials interact to maintain a normal and effective blood calcium level without allowing phosphorus levels to run away.
We'll review the story of how this works but it's complicated and we won't be offended if you skip to the Treatment section.
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 as dangerous as too little.
The thyroid gland lobes surround the windpipe (trachea)
WHEN THE BLOOD CALCIUM LEVEL DROPS, WE HAVE HORMONES TO BRING IT UP AGAIN
So PTH activates the very substance (calcitriol) that shuts it off. (Imagine a faucet that shuts off when the water level in the sink reaches a certain level. The faucet brings the water but the water shuts off the faucet). Both PTH and calcitriol raise calcium but once both PTH and calcitriol are shut off, calcium stops rising. It would seem to be a perfect system.
Parathyroid hormone activates calcitriol
When it comes to phosphorus, PTH and calcitriol no longer work together. PTH signals the kidney to dump phosphorus while calcitriol signals the kidney to save it. In the normal body, the coordination of these hormones works out to keep calcium and phosphorus levels in balance, no matter what is happening with the blood calcium.
All this goes along swimmingly until the kidney is too damaged to respond to its hormonal signals and too damaged to properly activate calcitriol.
Parathyroid hormone causes the kidney to dump phosphorus
WHAT HAPPENS IN KIDNEY FAILURE?
In early kidney failure, the kidney becomes unable to get rid of phosphorus normally and as a result phosphorus levels begin to rise. This activates a substance called Fibroblast Growth Factor 23 (affectionately known as "FGF-23") from the bones. FGF-23 encourages the kidney to dump more phosphorus and dampen activation of calcitriol (recall calcitriol tells the kidney to save phosphorus). As part of its mission to dampen calcitriol, FGF-23 also instructs the parathyroid glands to cut back on PTH. All this calcitriol suppression is all well and good and helps keep the phosphorus levels reasonable but pretty soon there is so little PTH and so little calcitriol that calcium begins to drop.
And this is where calcium-phosphorus Hell breaks loose.
At this point, kidney failure is no longer "early." Dropping calcium levels supersede any FGF-23-mediated suppression of PTH and the parathyroid glands crank up PTH production to bring calcium levels back up. To meet the body's demand for circulating calcium, the bones liberate their structural calcium to save the day but, unfortunately, doing this liberates more phosphorus. This leads to an even higher phosphorus level. Circulating phosphorus binds the circulating calcium creating crystals which deposit in the body's soft tissues and generate inflammation. Bones are weakened and replaced with fibrous tissue. Calcium is depositing uselessly all over the place and the parathyroid glands must crank even harder to keep calcium levels livable. A metabolic disaster has occurred at this point.
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?
The goal phosphorus level defined by the International Renal Interest Society is between 2.5 mg/dl and 6.0 mg/dl depending on the patient's stage of renal disease.
It is important to remember that ultimately phosphorus balance is a matter of balancing phosphorus entering the body with phosphorus leaving the body. If the kidney is no longer effective at removing phosphorus, we can perhaps work on limiting the amount of phosphorus entering the body. The first step in doing this is with a prescription renal diet. These diets are designed to give the kidney less work to do and that includes limiting phosphorus entering from the GI tract. After 1-2 months on a phosphorus restricted diet, blood tests will indicate whether or not additional phosphorus treatment is needed.
These are products given orally with food to bind the phosphorus in the food so that it cannot be absorbed into the body. This means they will not help an animal that is not eating and they will not help if they are not given in conjunction with a meal. Animals that graze on food through the day will need their phosphate binders mixed in the food.
There a number of phosphate binders available and which one is selected will depend in part on the concurrent calcium situation. This means that the ionized calcium level (not the total calcium level) must be measured. Some binders also supplement calcium while others drop or have no influence on calcium. Some patients require more than one binder to get their phosphorus value low enough.
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.
Renal secondary hyperparathyroidism and its associated high blood phosphate levels are one of the most common uremic toxin issues in the treatment of kidney disease. Dedication is required to get phosphate binders into the pet along with food when appetite itself is tenuous. Phosphate binders come in powders, liquids, capsules, compounded flavored chews and other formats. Consider what approach is likely to work best for your pet but, remember, the binder only works in the presence of food.
Other Pages in the Chronic Renal Failure Center: