Evidence Update: Azodyl for Chronic Kidney Disease in Dogs

One of the products I have kept track of over the years is Azodyl, a probiotic reported to be useful in treating kidney disease in dogs and cats. Though the company has reported positive results in laboratory studies involving rats, cats, and pigs, the independent studies so far reported in dogs and cats have not found any real-world benefits. Apparently last summer another study was presented at the ACVIM Forum, a conference for veterinary internal medicine specialists.

Kanakubo; S. Ross; H. Finke; J. Kirby; S. Nalor; C. Stafford; L.D. Cowgill. Influence of AzodylTM on Urea and Water Metabolism in Uremic Dogs. ACVIM Forum 2013, June 12-15,. Seattle, WA.28970

The study was not a clinical trial but a laboratory study of a small number of dogs (4) undergoing dialysis for treatment of kidney disease. The investigators evaluated the effects of Azodyl, given at two different doses over 1-2 months of time, by comparing various laboratory tests for measuring kidney function and the processing of nitrogen from protein in the diet in the same dogs before and after giving the probiotic. The study was partially funded by the manufacturer of Azodyl.

The investigators concluded that there were no changes in any of the measured values when these dogs were put on Azodyl. However, the dogs did appear to gain weight from fluid, suggesting that perhaps the product influenced water consumption or absorption.

 The results of this short-term study demonstrated:

  • AzodylTM had no significant or beneficial effect on pre-dialysis BUN in dialysis-dependent dogs.
  • AzodylTM had no significant effect on single treatment or weekly time-average urea, TACurea; urea appearance rate, Ga; or the whole-body urea clearance, Curea.
  • AzodylTM administration produced no demonstrable effect on the intestinal clearance of urea, Cint.
  • AzodylTM administration was associated with a positive increase in total body water requiring increased dialytic removal to maintain dry-weight.
  • Despite manufacturer’s suggestion, AzodylTM did not influence short-term azotemia or nitrogen metabolism in this CKD cohort.
  • AzodyTM was associated with a positive fluid balance in these dogs.
  • These results were unable to support the potential for AzodylTM to facilitate ‘Enteral Dialysis’ in dogs with CKD undergoing hemodialysis

 

This is a pretty small and unusual population of dogs compared to those who will normally be treated with Azodyl in routine clinical practice, so it does not determine whether or not the product is clinically useful in more typical cases. However, it does undermine some of the theoretical rationale for why Azodyl might be useful in chronic kidney disease in dogs.

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31 Responses to Evidence Update: Azodyl for Chronic Kidney Disease in Dogs

  1. Heart Broken says:

    My puppy was diagnostic with kidney disease at 5 months of age. We used Azodyl as directed. It did no good what so ever. It did not slow down the disease nor extend his life nor did it help him deal with the disease. He died at 10 1/2 months of age. While using this product he went from stage 2 to stage 5 in 2 1/2 months, and then well past. We kept him on it well past what was beneficial. He was a great pup, he would have been a great dog.

  2. kathy malloy says:

    Azodyl is super expense and my dog’s levels are not going down after 2 weeks, they were higher! My question is why can’t I give her my probiotics? A lot less expensive….
    Or what do you recommend??

  3. kathy malloy says:

    can you change my name to Wesleygg please??

  4. skeptvet says:

    The issue is that there is ZERO evidence that probiotics are helpful for dogs with renal disease, so whether you give azodyl or give another veterinary product or a human product really isn’t the point. WHile rpobiotics are helpful for some GI issues, there is not yet any reason to think they are worth giving for kidney failure. I would focus on treatments known to be helpful as listed under the IRIS guidelines for CKD treatment or consult your veterinarian about the specific needs or your pet.

    Good luck!

  5. skeptvet says:

    Sorry, I don’t actively manage the accounts of subscribers, so I have no idea how to change your user name.

  6. James says:

    I have a pair of English Bullies…. bro/sis 4-1/2 yrs old. I recently learned my male has smaller than normal kidneys…. this was diag only after the Eye DVM we see notice some abnormal urine reading in a pre-exam test. X-Ray confirmed kidney size. This vet specialist colleague, has recommended AZODYL probiotic, but after researching on my own, not sure this has any real value. Is there any current studies on this or other. Have visited/read CKD on IRIS web site.

    My normal vet, never picked on this condition, now insists I switch to the Science Diet KD food formula since he is a SD dealer. Grateful for any suggestions or other things I should be researching, besides a new Vet.

  7. skeptvet says:

    I’m not aware of any more recent research on probiotics for renal disease. There is, however, strong evidence that renal diets do have benefits, whether K/D or another brand, so I would try to make a transition to one of these if possible.

  8. Mary Rose Sweger says:

    My 11 year old Llhaspoo had blood work done which showed the early start of kidney problems. He eats L/D food and I was wondering what your views would be to switch him to the K/D food? Also how fast can kidney disease progress. thank you for your time.

  9. skeptvet says:

    Of course, decisions about therapy for kidney disease have to be made on an individual basis in consultation with your veterinarian. Kidney diets do have clear benefits when used appropriately, but I can’t give you specific recommendations for you pet. Progression of kidney disease is very unpredictable, so ths is something that has to be monitored in each case.

    Here is some good general information about kidney disease in dogs and cats. I would also make sure to find a vet you have a good, consistent relationship with to discuss your dog’s treatment options.

    Good luck!

  10. Kathy says:

    Used 1 time never again made my dog very tired not excited she was fine before I used it. She has kidney disease high bun was told it would lower bun used it 1x and next day but good at all. I would not recommend it at all.

  11. Jess says:

    My dog has been taking it for 2/years and its dome nothing for her levels. Dr. Harveys Diet and my own supplements of goats milk, and fish stock have helped immensely. Vets are not extensively trained on nutrition. So I would never go with RX food full of byproducts.

  12. skeptvet says:

    Actually, v, especially board-certified veterinary nutritionists. Your concern about the ingredients in these diets is misplaced and, unfortunately, created by unscientific misinformation out there about pet diets. Kidney diets have been shown by very robust evidence to improve quality and length of life in animals with kidney disease, and whether you do a homemade or commercial diet, it is always better to use a diet formulated for this problem.

  13. Fatima says:

    True! Dr. Harvey is really a savior, my dog has been on that and home cook diet and this is going to be his third year since diagnosed. Goat milk, vitamins and fish fatty acids are a must as well. It’s a lot of mindful feeding and work but totally worth it.

  14. Mesha says:

    Dr. Harvey is not a Veterinarian. His company portrays him as one. I don’t understand how it’s even legal.

  15. CKDDogMom says:

    What’s your opinion on Visbiome kidney claims?

  16. skeptvet says:

    Pretty limited and preliminary evidence, so not yet convincing. The web site lists one clinical study. In this, some measures differed between treatment and control groups (e.g. GFR, USG) and others did not (e.g. creatinine and BUN). It is unclear if the statistically significant differences that were seen are meaningful. For example, GFR varied by about 40 points among subjects, and the difference between before and after measurements were about 7-8 points. Is this a meaningful difference that would affect clinical symptoms or long-term survival? Who knows? The study didn’t look at these kinds of clinical outcomes, so all we have is a few biomarkers which differed, and this would have to be shown to be consistent in more studies and connected to real-world outcomes before we ca say if they are real and meaningful.

  17. Janice says:

    Hi my Eleven year old boxer was diagnosed about ten months ago and he was put on azodyl Along with fluid every other day and The c k diet either the hills or royal canaan. I too began to research things because of the expense of the food and I’ve figured out that vets actually get a kickback from that prescription food of course they’re going to prescribe it.
    But at the same time I would agree that the diet is the most important thing but as long as you do research and check all of the different ingredients. You can find the same diet in foods like square pet is 1 of them and I have gone to making my own dog food For the most part.
    Now that i’m seeing the research on azerdale i’m Confused whether or not that’s even helping him when he started on his medicine it did not change from when he 1st started to a month later the numbers were. Still the same even though hes doing OK
    So that makes me wonder if he is even benefiting anything from that I also saw someone on here that. Does? The same. Thing that I do I supplement with goats milk and salmon oil and that’s a must.
    I think we all just have to stick together on this and check and see what all’s new all the time.
    Also hills and Royal Canaan both have lawsuits against them. I think apparently they’re not regulated by the same places that the regular dog food is so they can do other things like one of them found poison in their. Food or something and there’s lawsuits but crazy against them. If it’s the only thing you have. I would say use those brands but I would also say research while you’re at it. Because there are many other ones that are just as good or actually better. I forget which one of those 2 named brands but 1 of them has almost all corn filler in it. Anyway everybody stays safe and prayers to all

  18. skeptvet says:

    “I’ve figured out that vets actually get a kickback from that prescription food of course they’re going to prescribe it.”
    You are wrong about this. Some vets do sell therapeutic diets directly, and they may add a markup on top of the price they pay in order to cover costs for storing and handling the food or eve, shockingly, to make a profit as they do run businesses. However, this is not a “kickback,” and many vets also simply provide written prescriptions for these diets so their clients can buy them elsewhere, for which they make nothing. The idea that vets would sell a food solely for the money it makes them regardless of whether or not it benefits their patients is a ridiculous and depreessingly cynical view of veterinarians which totally misunderstands who we are and what we care about.

    “But at the same time I would agree that the diet is the most important thing but as long as you do research and check all of the different ingredients. You can find the same diet in foods like square pet is 1 of them and I have gone to making my own dog food For the most part.”
    The effectiveness of kidney diets is not in their “ingredients” but in the formulation, meaning the relative proportions of specific macronutrients and micronutrients. Most homemade diet recipes for kidney disease ind dogs and cats are not accurate or appropriate, so if you want to make a diet at home, you should consult with a board-certified veterinary nutritionist to have a diet formulated specifically for your pet (you can find these experts offering this service online).

    “Thing that I do I supplement with goats milk and salmon oil and that’s a must.”
    No evidence to support this. Salmon oil is a source of omega 6 fatty acids, which might have some benefits, though recent research in humans has found such supplements not as helpful as was originally hoped. Goat’s milk is only appropriate for baby goats.

    “I think apparently they’re not regulated by the same places that the regular dog food is so they can do other things like one of them found poison in their. ”
    Again total nonsense. Sure, there are sometimes lawsuits against food companies, but they are regulated in the same way as all the others, and these lawsuits do not have anything to do with the issue of whether renal diets extend life in dogs with kidney disease (which they definitely do), nor do they mean that making up whatever we want to as an alternative is a good idea (which it is not).

  19. art malernee dvm says:

    Salmon oil is a source of omega 6 fatty acids>>> 3?

  20. skeptvet says:

    Yup, omega-3 is what I meant. Of course it has both, but the purported value is in the high proportion of the omega 3. Thanks!

  21. art william malernee says:

    i guess we might be running what we write through a chatgpt like fact checker before hitting the send button soon. Could be like we use a spell checker that underlines in red a typo. The computer program could underline in red the things we write that it thinks are not factual. May become scientific peer review better than just technical editing.

    artjamie@aol.com
    can you check and see if the following sentence is true? Salmon oil is a source of omega 6 fatty acids,
    I’m sorry, but that statement is not entirely accurate. Salmon oil is actually a source of omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are important for maintaining a healthy heart and brain. Omega-6 fatty acids are found in many vegetable oils, such as corn oil, soybean oil, and sunflower oil.

  22. Janice says:

    Thank you skepvet for replying…..

    I totally concede to the things that you said and I do not have evidence of vets making money on the food.
    I do know that from what I see there is no material in this ” prescription food” that makes me have to get a note from Dr. To purchase it so that alone says there’s more to it than them just wanting to feed them correctly. Also there’s no reason for the price to be so much more with what appears to me to be some everyday fillers in it.
    The goats milk has been studied to help your gut (humans also) with bacteria of some sort.
    I have a 14 yr old shitsu that has allergies and we battled cancer from (well probably from) the apoquel or steroids. Ever since starting him on goats milk not one visit to the vet for itching.
    But back to the ckd … I have no doubt that there are perfectly good people out there That are just wanting to help us but I also know there are not so good people out there trying to scam us and we have to be very vigilant on Helping each other by sharing info and what not.
    And I love arts idea … that would ve way better than getting banned for saying something because it is our right to speak lol
    The only issue with underlining it in red is who decides to underline it because there are many web sites that say the things I said before.
    I have an awesome vet. My ckd dog started out with my aunt so I kept her vet at first since he had gone there.
    I like your advice about the nutritionalist and my vet also advised that.
    Thank you again for helping so many people

  23. Margi Sancic says:

    16 years ago my vet recommended putting my 16 year old cat “to sleep “ due to advanced kidney disease. I went elsewhere to a vet who recommended Azodyl to give my cat a comfortable, likely 4 more years of life. There was a marked improvement in his life including a better appetite, weight gain, playfulness, and obvious comfort. He lived like that for 4 more years and then went down hill quickly and passed within a few months. The Vet never promised a cure, only improved quality of life and around 4 years of quality living. That’s what I got. I now have a 13 year old cat who has been diagnosed with the beginning stages of kidney disease and I am wondering if Azodyl is my best choice now or if something better has been developed? Being in stage 3 kidney disease myself, they don’t seem to be coming up with anything helpful for humans either….

  24. Hilary says:

    Janice,
    The reason you need a prescription for a therapeutic renal diet is because it does not meet the nutritional needs of animals who do not have CKD. For example, the phosphorus content of prescription renal diets is significantly lower than that of standard adult food. This is good for animals with CKD, who need reduced phosphorus, but it is too little phosphorus to meet the nutritional needs of healthy adult animals. Phosphorus a necessary nutrient and every animal needs it; a renal diet simply does not provide enough phosphorus for a healthy animal. This is why diets like these are prescription only: so that only the animals that need the reduced nutrients are fed the food, and so that uneducated pet guardians don’t feed them to healthy animals and make them sick through nutrient deficits. As has been referenced in this thread, it is not just the ingredients but the formulation, the ratio of those ingredients, that is important.

    While I understand your skepticism and complaint about price, there is a clear and logical reason for these diets to be prescription only: to make sure that they are given only to the animals that actually need them. You seem to have fallen under the influence of internet sources that demonize veterinarians and paint them as drug/diet pushers only out to make money. Please remember that most of the people spreading this opinion and advocating for alternatives to what vets recommend have no medical or scientific education and are themselves out to make money.

  25. George says:

    Hi, I have a cat somewhere in stage 2 with CKD.
    I am giving it specialized Royal canin food with Pronefra and I’ve started Azodyl as well.

    I am noticing somewhat a reduced appetite, not greatly reduced but still somewhat apparent and a loss of muscle mass. Ultimately, I am going to consult again with a vet about what I am going to ask here, but wanted to hear yall`s opinion also.

    Does anyone use appetite stimulants such as Mirataz? Are there any potential downsides of that medicine? I think I read somewhere that it can be damaging to kidneys, so it does seem like it could be a last resort solution, but at the same time in other places like here – http://www.iris-kidney.com/pdf/IRIS_CAT_Treatment_Recommendations_2023.pdf it says that it can be given as “early” as stage 2 of the disease.

    For the record, my cat is 12 years old.

  26. skeptvet says:

    Mirtazipine is commonly used for cats with CKD to stimulate appetite, and several studies have shown it can lead to weight gain. It is not dangerous to the kidneys, but because decreased kidney function slows the elimination of the drug, dosages have to be adjusted appropriately. Another appetite stimulant, capromorelin, may also be useful. Here are some studies to consider-

    Quimby JM, Lunn KF. Mirtazapine as an appetite stimulant and anti-emetic in cats with chronic kidney disease: a masked placebo-controlled crossover clinical trial. Vet J. 2013;197:651–655.

    Longpre K, Buhles W, Yin M, et al. Double-blind placebo-controlled, randomized study of transdermal mirtazapine ointment for the management of feline weight loss. J Vet Intern Med. 2017;31:110. (ACVIM Forum 2017).

    Quimby JM, Summers S, Benson KK, et al. Assessment of transdermal (Lipoderm) mirtazapine as an appetite stimulant in cats with chronic kidney disease. J Vet Intern Med. 2017;31:Late Breaking Abstract. (ACVIM Forum 2017).

    Zollers B, Allen J, Kennedy C, et al. Capromorelin, an orally active ghrelin agonist, caused sustained increases in IGF-1, increased food intake and body weight in cats. J Vet Intern Med. 2015;29:1219.

  27. Jo says:

    These are the ingredients of Hills Renal. Personally I don’t like unspecified ingredients. There are several renal diets made in Europe which have a straightforward ingredients listing. A friend devised a diet for her dog with the help of a vet trained in nutrition. The dog lived another 5 years until she was 16 and didn’t die of end stage kidney disease. The base was duck leg which is low in Phosphorus plus other ingredients such as sweet potato and appropriate supplementation.. The result was a meal that a human could enjoy. Her phosphorus levels remained low and the only meds she needed was for her BP. It was cheaper than Hills and as she froze the meals in batches so it was quite easy.

    The Hills is like UPF for dogs,

    COMPOSITION: Meat and animal derivatives (chicken 6%), derivatives of vegetable origin, oils and fats, various sugars, seeds, minerals, eggs and egg derivatives. Protein sources: Pork liver, chicken, dried eggs.

  28. skeptvet says:

    Not sure where you’re looking, but the ingredient list for K/D is on the Hill’s web site- https://www.hillspet.com/dog-food/pd-kd-canine-dry

    The problem with the logic here is that you can’t look at an ingredient list and judge the quality or medical impact of a diet. It’s like that BS about “if you can’t pronounce it, don’t eat it!” Our subjective feelings about “duck meat” vs “chicken fat” vs “Pyridoxine Hydrochloride” have nothing to do with the safety or nutritional value of a food including these ingredients. There is clinical trial evidence that renal diets extend lifespan and slow progression of kidney disease. That matters more than how we think the ingredient list sounds.

  29. Amanda says:

    Hello,

    I was wondering if there have been any more recent trials or studies for Azodyl? My 19 year old cat was just prescribed Azodyl, she has both high kidney and slightly high thyroid levels (that was all the vet told me) and is being switched to Hill Science y/d for the thyroid.

    From what I’m seeing it may cause her more harm trying to get her to take the Azodyl pill than any benefit that may come from it, however, the last trials/studies of any sort I can find are the ones you’ve mentioned here, and more generally about use of probiotics for cats and dogs altogether, the 2017 review by Jungan, et al (mentioned in the following), and your 2017 overview of evidence for probiotics in cats and dogs. So, has any further research been done that you know of? I’m sorry if I’ve missed something you already mentioned.

    Thank you for your time.

  30. skeptvet says:

    Hi Amanda,

    I have asked the company to provide any additional evidence they have (though I would expect them to feature supporting studies prominently on their site if they had they, so I am not optimistic).

    Here is what I’ve found in a quick search-

    A case report of three dogs in Japan. Since this is an uncontrolled report (no randomization, no placebo, no blinding, etc), it is essentially just set of well-documented anecdotes and subject to all kinds of bias. Did the dogs improve after starting the Azodyl because of the product or because they were given other treatments too and were being more carefully monitored and treated as part of a study? Who knows?

    This controlled study in 2010 in cats found no effects. Of course, proponents will argue it is invalid because the product was sprinkled on the food rather than given as an intact capsule. This might be true, or it might not, but it is still a clearly negative study with better methodology and bias control than anything that does support an effect of the product.

    I’ll keep an eye out for anything Vetoquinol sends me.

  31. skeptvet says:

    I was sent a link to the publications for Renadyl, the version of Azodyl marketed for humans. Most of this includes case reports, poster presentations, and other forms of low-level evidence. One small controlled clinical trial found a statistically significant reduction in BUN in 29/42 patients (I can’t say if this was clinically significant since I’m not an MD), and no significant changes in creatinine or uric acid. Another controlled trial is supposedly under way.

    So no new evidence to support use in dogs or cats, and very little, rather unconvincing evidence in humans. The most recent systematic review of probiotics, prebiotics, and synbiotics for people with chronic kidney disease concluded,

    We found very few studies that adequately test biotic supplementation as alternative treatments for improving kidney function, GI symptoms, dialysis outcomes, allograft function, patient-reported outcomes, CVD, cancer, reducing uraemic toxins, and adverse effects. We are not certain whether synbiotics, prebiotics, or probiotics are more or less effective compared to one another, antibiotics, or standard care for improving patient outcomes in people with CKD. Adverse events were uncommon and mild.

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