By Wendy C. Brooks, DVM, DipABVP
Educational Director, VeterinaryPartner.com
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 that 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 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, 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.
When The Blood Calcium Level Drops, We Have Hormones To Bring It Up Again
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 hormone encourages the activation of calcidiol (also called vitamin D2) into calcitriol (also called vitamin D3) by the kidney. More active calcitriol helps drive the blood calcium level up and, in turn, calcitriol is able to shut off the secretion of parathyroid hormone so that this cascade does not get out of hand.
Parathyroid hormone activates calcitriol, which in turn shuts off parathyroid hormone secretion to keep the cascade from getting out of hand.
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 while vitamin D causes the kidney to save 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 (a message that falls on deaf ears since the kidney is damaged and cannot comply) and dampens activation of vitamin D (which would normally encourage the kidney to retain phosphorus) and dampens PTH production. As the kidney becomes more diseased, FGF-23 becomes less and less effective and soon there is so little PTH and vitamin D that calcium begins to drop.
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 also 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 from getting out of control in the first place. If this is not possible, the goal is to get the phosphorus level back under control and keep it there.
How Do We Control Phosphorus Levels?
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. Hydrating a damaged kidney effectively maximizes the kidney's remaining function and this may be enough to control phosphorus.
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 therapeutic 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 one to two months on a phosphorus-restricted diet, blood tests will indicate whether or not additional phosphorus treatment is needed.
These are products given 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 won't 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 calcitriol 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.
- Calcitriol cannot be used in patients with elevated blood calcium levels.
- Calcitriol cannot be used in patients with phosphorus levels that are already abnormal. This is a preventive measure more than a treatment.