One of the first things the vet gave me to give to Eric was Renafood, a supplement consisting of various detoxifiers, including beet juice. I’m skeptical that it actually does anything for two main reasons:

1. I feel doubtful about the efficacy of herbal detoxification in general, partly stemming from a skepticism about the quality control and potency of the herbs in any given supplement, and partly stemming from skepticism that herbal detoxification actually works in the way described. I mean, look: my cat’s kidneys are fucked. Thoroughly, utterly fucked. I’m not sure how or why minute amounts of carrot and beet might help him filter waste material more effectively, unless they’re somehow rebuilding his nephrons for him.

2. The logic of some of the claims presented in the Renafood information sheet. So, Renafood contains bovine kidney extract. That extract apparently holds “tissue cell determinants” that will instruct the kidneys to Shape Up, Son. I have no idea what a “tissue cell determinant” is, though I have a very vague memory of learning about cell fate determination—thanks, high school biology! But the information sheet doesn’t give any sort of helpful definition of what these tissue cell determinants do other than talking about something that sort of vaguely sounds like cell fate determination. Quoting from the information sheet:

The bovine kidney PMG extract found in Renafood contains cellular determinants that regulate cell activities. Genetic coding determines the proteins unique to cells in each tissue, gland and organ. Cellular proteins are the foundation of the cell’s nutrition. Similarly, bovine kidney contributes innumerable materials produced in the organ itself, such as acids, enzymes and hormone precursors—each captured and preserved to offer their innate benefits to the corresponding tissues in humans to promote optimal health.

Huh. That sure sounds like a fancy way of saying…nothing much. Prepare for a bulleted list!

  • The first sentence makes an assertion that the cell determinants in Renafood regulate activities, and the next sentence is a more-or-less correct statement about cell fate determination, but doesn’t tell me how Renafood affects the genetic coding of cells.
  • The sentence after that reads like a complete non-sequitur. Cellular proteins may or may not be the foundation of a cell’s nutrition (I don’t know enough about biochemistry to begin unraveling what this deceptively simple sentence means), but how does that relate to the thesis sentence or to the conclusion?
  • Furthermore, what do they mean by “cellular proteins,” especially in this context?
  • The first part of the last sentence is more-or-less true, because it’s essentially talking about the kidney extract providing proteins, fats and vitamins, but you can feed real food (like, oh, I don’t know, fresh kidney) and, if the Renafood claims are true, get the same effect.
  • This information sheet from Standard Process explains what cell determinants do and how they relate to protomorphogens (which is apparently what constitutes the bovine kidney extract in Renafood), but it sounds even more gobbledegooky. The cell determinants in protomorphogens are apparently the mineral templates on which chromosomes are constructed. This is, near as I can determine (and I’ve confirmed this with biochemist friends just to make sure I didn’t miss something about cell biology) complete nonsense. Seriously.
  • I’ve read the info sheet through three times, and I’m still not entirely sure how Renafood keeps cells healthy or helps regenerate cells, because I don’t see how the leap from digestive system to bloodstream to cell division is made—there’s a lot of talk about “affinity” and thermostability and how important cell determinant are, but very little actual science. The most credible-sounding scientific bits aren’t supported by any references, and most importantly, they’re not connected to how the supplement’s supposed to work. Speaking as a former technical writer, this is probably the shoddiest bit of technical writing I’ve ever seen.
  • It doesn’t help that Royal Lee, the founder of Standard Process, has been prosecuted for criminal misbranding. The FDA has in the past characterized him as “probably the largest publisher of unreliable and false nutritional information in the world.” Given how lackadaisical the FDA has been and continues to be about food and drug regulation, these aren’t just fightin’ words, them’s strong fightin’ words.
  • Taken as a whole, it sounds like Standard Prociess is claiming that eating Renafood will somehow stimulate kidney cells to work better through a mysterious process involving “cellular determinants.” If that’s not science-esque, I don’t know what is. (“Science-esque 2: This time, it’s not Science-esque 1!”)

In short: I’m not sure I buy into the idea that this does anything. I’m giving it to Eric right now because he loves it, and it doesn’t contain anything that seems overtly harmful. But my woo-woo meter is on alert, and if you want to save yourself $16, I’d argue that this supplement doesn’t do anything other than provide a nice source of vitamin A and a tasty snack.

Using Nutritional Yeast in Feline Renal Failure Diets

I stopped feeding nutritional yeast a while back, because I was feeding quite a bit of canned food and quite a bit of liver. However, given that liver contains a higher phosphorus-to-B-vitamin ratio, and given the fact that I’m feeding my cats canned food maybe once every ten days now, I’m feeding about twice the nutritional yeast than I normally would, i.e., almost two teaspoons per cat per day.

Several reasons why I’m doing this:

1. Eric’s peeing a whole lot, which means he’s losing a lot of water-soluble vitamins, like B vitamins. Nutritional yeast contains a LOT of B vitamins. Here’s a some relevant information (lifted from; quantities are per heaping tablespoonful, which is close to what I feed total for both cats every day:

Thiamin (B1): 9.6 mg
Riboflavin (B2): 9.6 mg
Niacin: 56 mg
Vitamin B6: 9.6 mg
Folic Acid: 240 mcg
Vitamin B12: 8 mcg
Biotin: 20.8 mcg
Pantothenic Acid: 1.04 mg
Phosphorus: 174.4 mg
Calcium: 11.2 mg

I initially wanted to find a meat-based food source of B vitamins, and what popped to mind immediate was chicken liver. But chicken liver can’t even come close. Here’s the B-vitamin profile for two ounces of liver (approximate 7 grams)—again, I’m approximating how much I’d feed to both cats per day:

Calcium: 5 mg
Phosphorus: 169 mg
Thiamin: 0.174 mg
Riboflavin: 1.013 mg
Niacin: 5.545 mg
Pantothenic acid: 3.553 mg
Vitamin B-6: 0.486 mg
Folate, total: 335 mcg
Folic acid: 0 mcg
Folate, food: 335 mcg
Choline, total: 110.8 mg
Vitamin B-12: 9.45 mcg

So about the same amount of phosphorus between the nutritional yeast and the liver, but except for B-12, folate and pantothenic acid, the nutritional yeast gives more B-complex bang for the buck (and it’s a pretty close match for the B-12). The USDA National Nutrient Database doesn’t give the value for biotin in liver, so I don’t know how that compares in chicken liver vs. nutritional yeast, but I’m feeding egg yolks on a regular basis, so I know the cats are getting plenty of biotin no matter what.

2. Wow. That was a really long point. This second one is much shorter, I promise, and it boils down to this: Both cats really love the taste, but Eric loves it. And I mean, he really, really loves it. More than a fat kid loves cake. And given his depressed appetite, I’m perfectly happy to indulge him in this for as long as he’s around, and as long as it keeps him happy and eating.

3. Again, because of the increased peeing, Eric’s losing more potassium than he should. A heaping tablespoonful of yeast contains 320 mg of potassium and 5.2 mg of sodium. (Chicken liver is pretty good, too, but not quite as good; two ounces contains 131 mg of potassium and 40 mg of sodium.) That’s pretty much perfect: lots of potassium to make up for what he’s losing, and relatively little salt, because cats with chronic kidney disease often have difficulty eliminating sodium, which can sometimes result in high blood pressure.

4. Eric’s phosphorus and calcium levels are normal. I wouldn’t feed this to a cat with elevated phosphorus, or at least, I wouldn’t feed it without a phosphorus binder. I’d go with a B-complex vitamin supplement instead. But I want to keep his nutritional supplementation as food-based as possible for now. Note that this choice is a decision based more on philosophy than science, driven largely by my opinion that food will provide better nutrition than, well, bare, isolated nutrients.

To feed, or not to feed? That is the question.
Whether ’tis nobler to suffer the slings and arrows of yeasty misfortune… OK. Right. Sorry about that. At any rate, I’ve heard people express concern about feeding nutritional yeast as a dietary staple, but I have yet to read an explanation that makes sense to me. It’s definitely high in phosphorus, but you can compensate for that in a home-made diet by ensuring you’re providing enough calcium.  There’s some talk about how it’s a cheap by-product of beer brewing, but that’s brewer’s yeast. From what I understand, they’re the same species (Saccharomyces cerevisiae), but nutritional yeast is grown and killed solely as a nutritional supplement and isn’t used for brewing first. (I’ve read conflicting information on this, and will be more than happy to be corrected.)

I’ve read other people expressing concerns about it “fermenting” in the stomach (Feline Future used to claim this, but seems to have backed off since then), which: what? First of all, it’s completely deactivated, which means it’s dead—it can’t reproduce and actually, y’know, ferment. Now, if we’re talking about live yeast, like baker’s yeast or active brewer’s yeast, that would be a different matter entirely; I knew somebody whose dog stole and ate two batches of raw bread dough (labradors, man) and had to be taken to the ER because the bread started expanding in his stomach. So if there’s going to be any fermentation, that means microorganisms acting on the dead yeast as a substrate.

Now, nutritional yeast is pretty high-protein (about 50% of it consists of protein dry weight), and over half of its carbohydrate content is fiber. Protein, as far as I know, generally isn’t fermented; most fermentation tends to happen with carbohydrates. But the amount of digestible carbohydrate in  nutritional yeast is pretty marginal (3.3 g per heaping tablespoon) and the fiber may or may not be fermentable. If the fiber is fermentable, it’ll probably be fermented by bacteria in the colon, not in the stomach because feline stomachs are relatively sterile environments. But fermentation in the colon isn’t necessarily a bad thing—in fact, depending on the degree of fermentability, it could actually be a good thing. (Note to self: find out whether the fiber in nutritional yeast is soluble/insoluble, fermentable/non-fermentable).

However, if somebody has heard any sort of warning about nutritional yeast that’s backed up by something that makes scientific sense, I’m all ears. For now, my Google-fu hasn’t really turned up anything I need to watch out for.

Calcitriol therapy for chronic kidney disease

Calcitriol molecule
Calcitriol molecule

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.

On Squash, Fermentable Fiber and Feline Kidney Disease

One of the squashes from our garden
One of the squashes from our garden

One of the things I did to modify Eric’s diet after finding out about his polycystic kidneys was to reintroduce squash into his diet. In the past several years, I had dropped feeding vegetables to my cats entirely, largely because I was feeding them whole ground animals and canned Wellness and Evo on the side. I figured that the canned food was providing plenty of vegetable matter. Now that Eric’s sick, however, I’m much more draconian about feeding mostly raw food—partly because it’s better for him, and partly because Eric prefers it over the canned, which is strange because in the past his sole food preference, near as I could tell, was HOORAY FOOD OM NOM NOM NOM.

I added the squash back into Eric’s diet largely because I remembered reading back in the day that squash helps trap nitrogenous waste that would otherwise make it into the bloodstream. Today I went on an article hunt to see whether this had any sort of scientific basis, or if it was one of those raw feeding myths that get passed around because it sounds so damn good.

Assessing the Evidence

Therapeutic use of fiber in chronic kidney disease (or, if you’re old-school, chronic renal failure) is much more well-studied in humans than it is in cats. There seems to be some evidence that the consumption of soluble/fermentable fiber leads to increased excretion of nitrogen via poopin’ vs. peein’, thus lowering the amount of nitrogenous waste circulating in the blood and therefore eliminated by the kidneys. But what about cats?

I’ve found one decently reliable study that specifically looks at cats. It’s by researchers at Iams, so it’s not exactly woo-woo; research from the Iams lab is about as mainstream as it gets. The researchers found that feeding moderately fermentable fiber (mostly beet pulp and fructo-oligosaccharides) to cats decreased serum nitrogenous waste and increased fecal nitrogen excretion. The study proposed the following hypothesis as to why this would happen:

The beneficial bacteria in the cat’s lower intestine feed on the moderately fermentable fiber, creating short-chain fatty acids (SCFAs) in the process. SCFAs not only do all sorts of nifty things, such as keep the intestine cells happy and healthy, they also increase blood flow. The increased blood flow to the intestine results in more urea being circulated to the intestines, and the bacteria, which also produce urease (an enzyme that denatures urea), convert the nitrogenous wastes to carbon dioxide and ammonia, which are then incorporated into the bacteria themselves and then pooped out by the cat, as opposed to circulating to the kidneys to be peed out.

This sounds really good and really plausible, and the results show pretty unequivocally that fermentable fiber helps reduce the urea load in the serum, which means less work for damaged kidneys, but keep these things in mind:

1. This study is really small, involving only sixteen cats.

2. They were fed the diets containing fermentable fiber for relatively short periods of time—two weeks total for with an active waste collection period of eight days.

3. The decreased waste could be due in part to the decrease in protein digestibility. The study noted that the protein digestibility decreased to 87-91% with the fermentable fiber blends.

4. As far as I could tell, they didn’t actually actually draw any blood and run blood panels; they looked at urine and feces only.

So the verdict right now is: it probably does help a little bit, but as with anything scientific, the people in the white coats need to study it more. Given that steamed squash doesn’t contain anything harmful to cats, and given the potential benefits vs. potential dangers (yes, there’s a decrease in protein digestibility from the fiber, but Eric’s getting so much high-quality protein in his food that I’m not worried about marginal decreases at this point), I decided to go ahead and give Eric a heaping tablespoonful of pureed squash per day, which comes to about 10-15% of his total food. I created a mix from a gem squash harvested straight from my garden and organic butternut from the store. He loves it. I don’t need to mix it in with the food; it’s a lurid orange dot amidst the raw rabbit and Nature’s Variety, and he often eats it first. I suppose we’ll find out whether it does anything when we test his blood again in January.

Fiber Content for Various Squash Species

If you’re curious about the fiber content of different species of squash, here’s the information I looked up on the USDA National Nutrient Database per 100 grams of raw squash (unless otherwise noted):

Butternut squash: 2.0 g  (86.41% water)
Acorn squash: 1.5 g (87.78% water)
Generic winter squash: 1.5 g (89.76% water)
Pumpkin: 0.5 g (91.6% water)
Canned pumpkin: 2.9 g (89.97% water)

Canned pumpkin has almost double the fiber content of raw butternut (on a dry matter basis) and six times more than raw pumpkin, which is interesting. It looks like you can get more bang for the buck by feeding canned pumpkin. Eric likes the fresh stuff much better, however, so I’m sticking with it for now.