Calcitriol therapy for chronic kidney disease

If you want to read about all the different things I’m doing for Eric to help control the symptoms of his polycystic kidney disease, check out the diet modification and polycystic kidney disease tags.

Given the terrible shape of Eric’s kidneys, it became pretty clear to both the vet and me that we needed to take some pretty decisive steps to control his symptoms; however, neither of us wanted to go with the “throw everything at Eric and see what sticks” approach. We considered and rejected the following ideas:

• Using an ACE inhibitor to control blood pressure and proteinuria (largely because there’s no protein in his urine—yet)
• Subcutaneous fluids (he hates, hates, hates being stuck and the stress almost definitely isn’t going to be worth the benefit)
• Phosphate binders (his blood phosphorus is completely normal)
• Restricting his protein intake. Protein restriction is a really bad idea for cats, even sick cats. So far, all the studies I’ve encountered that advocate strongly for a limited protein diet for CRF cats either 1) inferred this from rat and human studies, or 2) failed to distinguish between the effects of high protein intake vs. high phosphorus intake. I’ll write a more detailed post in the future about the importance of maintaining protein intake, even in the face of renal failure.

That’s not to say that we won’t consider using ACE inhibitors and phosphate binders in the future. We’re drawing blood every couple months and monitoring him closely, and we’ll change our course accordingly depending on what the bloodwork tells us.

However, Eric is an excellent candidate for is calcitriol, which I’ve been giving it to him since last week, and so far, it seems to be working quite nicely.

What’s calcitriol?
It’s the most biologically active form of vitamin D. Vitamin D’s most basic form is as a vitamin precursor (7-dehydrocholesterol is the type found in animal tissue, for the geeks in the crowd). After ingestion, 7-dehydrocholesterol is normally transported to the skin, where UV radiation helps convert it to another form of vitamin D, cholecalciferol. When you buy vitamin D supplements, it normally comes in the form of cholecalciferol; cholecalciferol is also found in animal tissue, like liver and egg yolk. Now, cats are by and large unable to convert 7-dehydrocholesterol to cholecalciferol, which means they need to ingest cholecalciferol to meet their vitamin D needs. This normally presents no problems whatsoever, because animal tissue provides plenty.

However, cholecalciferol needs to make two stops before it becomes biologically active:

1. It stops in the liver, which adds a hydroxyl group and turns it into calcidiol.

2. It makes a final stop in the kidneys, which adds another hydroxyl group and turns it into its active form, calcitriol.

Why give it to a cat with chronic kidney disease?
So, cats with chronic kidney disease often get into a Spiral of Doom with phosphorus, calcium and vitamin D. That’s partly because mammals depend on vitamin D for proper regulation of phosphorus and calcium levels, and vitamin D requires proper kidney function in order to become calcitriol.

So here’s how the Cycle of Doom starts when a cat’s kidneys are in such bad shape that he’s showing signs of renal failure:

Calcitriol levels start dropping, because the kidneys can no longer produce adequate amounts. In response, blood calcium levels begin to drop, and phosphorus levels start to rise.

In response to the drop in blood calcium levels, the cat’s parathyroid glands start releasing parathyroid hormone *PTH). This hormone stimulates calcitriol production in the kidneys, mobilizes calcium from bones to help raise blood calcium levels, and encourages the kidneys to excrete phosphorus while retaining calcium.

But the kidneys are completely wrecked–they’re Scotty, trying to tell Kirk that they’re giving it all they can, cap’n, but they cannae do it. After a while, so much phosphorus is swimming around in the blood that it begins combining with calcium to produce calcium phosphate crystals, which are deposited in the soft tissue and proceed to inflame the tissue and otherwise behave like hooligans. In the meanwhile, blood calcium drops lower than ever because it’s now being bound by the phosphorus, and the PTH instructs the body to withdraw calcium from bones in a desperate attempt to keep SOME calcium in the bloodstream, which seriously weakens the integrity of the bone structure.

So yeah. Doom. Doomy doom DOOOOOOM.

But this cycle can be averted if you administer calcitriol before the metabolic screwiness begins—that is, before blood phosphorus levels start climbing and before the blood calcium drops precipitously. See, calcitriol controls the amount of PTH circulating in the bloodstream, because a sufficient quantity of calcitriol is a signal to the parathyroid gland to stop secreting PTH, effectively nipping the destructive cycle in the bud. The amount of calcitriol you need to give is incredibly minuscule, because you want to keep the parathyroid glands happy; you don’t really want to affect either the calcium or phosphorus levels in the blood.

So how little is “incredibly minuscule”?
Eric is getting 12.5 nanograms a day right now. Yup, you read that right: nanograms. He’s getting 12.5 billionths of a gram.

Any downsides and side-effects to giving calcitriol?

• Hypercalcemia (elevated calcium levels) is one of the dangers of calcitriol therapy, which, if you allow to continue unchecked, can lead to all sorts of problems. This means that if your cat’s bloodwork shows elevated calcium to begin with, calcitriol therapy is a pretty terrible idea.
• If you’re giving a phosphorus binder that contains calcium, it’s probably not the greatest idea to throw calcitriol on top of that, too.
• Furthermore, if your cat’s phosphorus levels are high,  giving calcitriol may be a bad idea, because calcitriol encourages the kidneys to retain phosphorus and increases the absorption of phosphorus from the gastrointestinal tract. Eric’s calcium and phosphorus levels were normal, which makes him an ideal candidate. We’re going to follow up with a blood draw in two weeks to make sure his calcium levels aren’t dangerously elevated.
• I just want to stress that regular bloodwork is a sensible idea for cats with any kind of chronic kidney disease in general, but when you’re administering substances like calcitriol, which can potentially alter critical blood values in already sick cats, you should definitely schedule a couple of follow-up blood tests a couple weeks after starting the meds and very closely monitor your cat for changes in appetite and other behavior.
• It also seems to give Eric mild nausea that lasts a couple of hours, so I’m feeding it mixed up in a teaspoon of canned Wellness Kitten, and splitting it into two doses given 2 hours apart, with dinner right in between. That seems to help. The reaction may be due to the tuna-flavored oil suspension that it comes in, however, as opposed to the calcitriol per se.

Noticed any changes since starting calcitriol?
Eric’s energy levels and appetite have shot up since starting calcitriol, and that makes me a happy camper. He actually knocked over the garbage a couple days ago, something he hasn’t done in months. At first, I was all “RAAAAAGE!” but then I realized that this meant he was feeling sassy again, and was all “Awwww, he must be feeling better.” Who knew I’d be happy about something like that, eh?

I’m waiting to make a final judgment when I see the bloodwork results in a few weeks, but so far, I’m pretty happy with the changes I’ve noticed. If your chronic renal failure kitty’s bloodwork shows normal phosphorus and calcium values, talk to your vet about the possibility of calcitriol therapy.

References I used and works linked to in this post:
Small Animal Clinical Nutrition, 4th Ed., by Michael S. Hand, Craig D. Thatcher, Rebecca L. Remillard & Philip Roudebush. Mark Morris Institute, 2000.

The Mar Vista Animal Center page on calcitriol and its therapeutic use in kidney failure.

The Wikipedia page on calcitriol.

“Ineffective Vitamin D Synthesis in Cats Is Reversed by an Inhibitor of 7-Dehydrocholestrol-Δ⁷-Reductase” by James G. Morris, published in Journal of Nutrition, vol. 129, pp. 903-908, 1999.