Medical Treatment for Dogs with Kidney Disease
More Info: Tanya's Comprehensive Guide to Feline Chronic Renal Failure: Treatments (even though this site is devoted to cats, most of the information also applies to dogs).
Disclaimer: I am not a veterinarian, nor do I have any formal training in any medical field. The information presented here is not meant to replace your vet's advice or prescribed medications, but only to suggest additional options to explore, based on your dog's condition.
Phosphate binders should always be given with meals, to help bind the phosphorus in each meal.
Phosphate binders commonly use calcium (carbonate, citrate, or acetate) or aluminum hydroxide. Note that calcium citrate and other forms of citrate may enhance uptake of aluminum hydroxide, though in most cases this doesn't seem to be a problem in dogs.
Calcium can be used as a phosphorus binder, but only if ionized calcium levels in the blood are normal and not elevated (hypercalcemia). Calcium is not as effective as aluminum-based binders, so is is best used when phosphorus levels are still normal (6.0 or below). The most effective calcium binder is Phoslo (calcium acetate, available by prescription only), but plain calcium carbonate, such as from ground eggshells, or other forms of calcium can be used when phosphorus levels in the blood are normal. Calcium acetate has the strongest phosphorus-binding ability, requiring about 40% less calcium to bind the same amount of phosphorus, and is less likely to lead to high calcium levels in the blood.
More information about calcium:
- One large eggshell makes about one teaspoon of ground eggshell, and contains about 5,000 mg calcium carbonate, which yields 2,000 mg elemental calcium per teaspoon. You can dry eggshells after washing them out, then grind them in a coffee grinder.
- You can also buy plain calcium carbonate in powder form, such as NOW Calcium Carbonate Powder, or in tablet form. Regular Strength Tums contains 200 mg elemental calcium per tablet, while Extra Strength has 300 mg and Ultra strength has 400 mg calcium per tablet (they also contain sucrose and other ingredients, so it's better to use plain calcium carbonate instead). Other forms of calcium are also fine to use, such as calcium lactate and calcium citrate.
- Animal Essentials Seaweed Calcium (available at Amazon) contains just 1.5 mg of phosphorus per 1,000 mg of calcium. It also supplies magnesium and iodine, which is good. Never use bone meal, dicalcium phosphate, or other calcium supplements that also include high amounts of phosphorus.
- Do NOT use antacids that also include magnesium, such as Mylanta.
- If your dog has normal calcium and phosphorus blood levels, add about 1,000 mg (1 gram) elemental calcium (1/2 teaspoon ground eggshell) per pound of food fed. As you restrict the amount of phosphorus in the diet more and more as kidney disease progresses, this amount of calcium should provide a ratio that ranges between 2:1 and 3:1 calcium:phosphorus.
- If you know how to calculate the amount of calcium and phosphorus in the diet that you're feeding, then use a ratio of about 3:1 calcium to phosphorus (this is the ratio used in Hill's k/d, for example).
- When blood phosphorus levels are elevated despite dietary phosphorus restriction, additional calcium or aluminum-based binders are added. Starting dosage is 30 mg/kg (15 mg/lb) of body weight daily, split between and always given with meals, for dogs with early- to moderate-stage kidney disease when phosphorus levels are not higher than 6.0. The amount of calcium may increase to as much as 100 mg calcium per kg of body weight if using calcium carbonate (60 mg/kg if using calcium acetate) daily. This is equivalent to 45 mg/lb of body weight for calcium carbonate (27 mg/lb if using calcium acetate). This amount is in addition to the 1,000 mg of calcium per pound of food that is added to the diet for balance, if you are feeding a homemade diet. If phosphorus values remain high when using calcium-based binders, you should switch to aluminum-based binders. Ask your vet for more information.
- When phosphorus levels in the blood are 8.0 or above, the dosage of aluminum hydroxide may go as high as 200 mg/kg daily, split between meals. See Dr. Nagode's Phosphorus Binder Protocol/Dosage.
- It takes around a month for blood phosphorus levels to stabilize after you change the diet or add phosphate binders, so rechecking levels too soon may be misleading regarding the effectiveness of the treatment.
- Reference: "Phosphorus restriction in the treatment of chronic renal failure" by D.J. Chew, S.P. DiBartola, L.A. Nagode, and R.J. Starkey.
"The appropriate dose of phosphate binder must be determined by monitoring individual patient response, but approximately 100mg/kg/day divided b.i.d. or t.i.d.[45 mg/pound of body weight daily divided into two or three doses] and administered with meals is a starting dosage for aluminum- and calcium- containing phosphate binders when serum phosphorus concentration is greater than 6.0 mg/dl. Lower dosages (30-90 mg/kg/day) may suffice during early CRF, characterized by normal serum phosphorus concentration. Because calcium acetate is more efficient than calcium carbonate in binding intestinal phosphorus on a basis of phosphorus bound/calcium absorbed (Mai et al. 1989), lower doses may be considered. Based on its higher molecular weight and higher phosphorus-binding ratio, it appears that a dose of calcium acetate at approximately 60 mg/kg/day will provide the amount of intestinal phosphorus binding as 100 mg/kg/day of calcium carbonate....Doses of calcium salts must be decreased if hypercalcemia develops." Remember that this is in addition to the amount of calcium in the diet.
- Reference: Phosphatemia: Management in the Treatment of Chronic Kidney Disease, A Roundtable Discussion. They suggest setting a target of 6 mg/dl blood phosphorus level at one month after initiating a phosphorus-restricted diet, and 4.5 mg/dl at two months. If you are above 6 mg/dl at one month, or below 6.0 but above the target level (see top of this section) after two months, then add a phosphate binder. If phosphorus levels are still above the target level after another month, increase the dosage of the binder.
Epakitin is a new form of phosphorus binder that is becoming more commonly used, though it is questionable how effective it is at binding phosphorus. See below for more info.
A new product for cats, Renalzin, uses lanthanum carbonate. Renalzin was introduced in Germany and the UK in October, 2008. It is not yet available in the US. Lanthanum carbonate is used in the human product, Fosrenol, which was approved by the FDA in 2004. It does not appear to be available in the US, and is extremely expensive.
Renagel (sevelamer hydrochloride), which does not contain either calcium or aluminum, is now being used for people. It has not yet been approved for dogs, though some have used it.
All phosphate binders need to be given WITH food (or immediately after) in order to block the excess phosphorus in the food from entering the bloodstream. Give away from other medications (by at least 1 hour, if possible) since antacids may effect absorption. Dosage depends on how bad the phosphorus values are.
See Phosphate Binders: What Are They and How Do They Work? for more information (human oriented). About Phosphorus Binders also has good information on this subject (feline oriented). Although I have no idea if it applies to dogs, apparently people become itchy when their phosphorus levels are too high.
Epakitin, a phosphorus binder, and Azodyl, a probiotic supplement that can help reduce urea nitrogen levels in the blood.
Epakitin (also marketed as Ipakitine in Europe) is a chitosan-based phosphate binder and uremic reducer. It contains lactose, calcium carbonate (the same form of calcium found in ground eggshells), chitosan, and hydrolyzed soy protein. The amount of calcium is pretty small, only 37 mg per gram of powder according to this analysis. Epakitin is administered at the rate of 1 gram per 5 kg (11 lbs) of body weight twice daily. It is the Chitosan that is the primary active ingredient, according to their literature. Chitosan is derived from shellfish and is the major source of the nutritional supplement glucosamine. PDRHealth says, "In animal models of chronic renal failure, chitosan produced decreases in serum urea nitrogen, serum creatine and serum phosphate." Note that chitosan can also be given by itself. There is some more information about Epakitin on the Phosphorus Binders web page of the CRF site for cats.
Epakitin comes in 50, 150 and 300 gram sizes, dosage is two scoops per 10 lbs of body weight divided evenly between meals. There is apparently 1 gram per scoop, so you will use around 60 grams per 10 lbs of body weight per month. The best prices I saw were at PSC Pets and Amazon.
See SupplementWatch for additional information on Chitosan. Chitosan is also marketed as a weight loss product (Vitacost, Now Foods), so you might be able to find it cheaper, but I'm not sure what the dosage would be, nor whether it would be as effective.
The owner of ThrivingPets.com, who has done some research on this product, says, "My research on Epakitin revealed that the product is more than 80% lactose. Epakitin is less than 10% calcium carbonate, so it is hard to even refer to this product as a calcium-based phosphorus binder -- in fact Vetoquinol doesn't, they call it a 'nutritional supplement.' Perhaps chitosan may be of some value to CRF pets, but here again the quantities are very small, as this fiber makes up less than 5% of the product."
If dosage of Epakitin is 2 grams (2,000 mg) per 10 lbs of body weight daily, 5% would be 100 mg chitosan per 10lbs of body weight daily (split evenly between meals). If Epakitin is prohibitively expensive for your size dog, you could try giving plain chitosan at this dosage instead.
I see no harm in using Epakitin, and some people feel it has helped their dogs, but if phosphorus levels are above normal, you should be using calcium or aluminum binders in place of or in addition to Epakitin.
Azodyl is a proprietary probiotic product that claims to help break down the by-products of digestion that contribute to uremia (elevated creatinine and BUN). Note that uremia contributes to symptoms of kidney disease, but is not harmful to the kidneys themselves; elevated creatinine and BUN are the result of kidney disease, not the cause. The bacteria are called "Kibow probiotics," from Kibow Biotech in Pennsylvania, which sells the same product under its own brand name, and says it contains three strands of probiotics: streptococcus thermophilus (now called Enterococcus thermophilus), lactobacillus acidophilus, and bifidobacterium longum, plus psyllium (prebiotic, used to feed the probiotics). See this info in their brochure. This company apparently patented the term "enteric dialysis" that is used to market Azodyl. Once again, you may be able to find these ingredients more cheaply in other probiotics products, such as Source Naturals Life Flora, Udo's Choice (available thru Amazon), and Stonyfield Farm Yogurt. See this Consumer Lab report for other good probiotic brands. Also see PDRHealth for more general info on these and other probiotic strains.
This product must be shipped cold, which can add considerably to the shipping cost. Best prices I found were at PSC Pets (free shipping if order is over $50, can add extra cold protection for $5) and Amazon. Order multiple bottles to reduce the shipping cost per bottle.
The Vetoquinol web site shows two small, unpublished and undated studies, one on pigs and one on cats (the one on cats was uncontrolled, neither was double-blind), showing some benefit from the use of Azodyl. I know of no other information that would suggest this product is beneficial to dogs with kidney disease, though there would be no harm in using it and probiotics offer other benefits as well. The owner of ThrivingPets.com, who agrees that the claims for Azodyl are overblown, still says, "I don't think Azodyl is a bad product. I think it can help with inappetence issues and improve digestion and absorption of nutrients. I don't think it will improve BUN and Creatinine but it may make your pet eat better and feel better which may lead to a better quality of life and may extend the pet's life as well."
I've heard several direct reports from people who feel Azodyl has helped their dogs:
- One person reported that her dog's BUN and creatinine were reduced after one month on the supplement.
- Another said it helped her dog with vomiting and diarrhea, but did not do any tests.
- One had to increase the dosage above the recommended amount, but then saw noticeable improvement in appetite and energy.
- One felt this product enhanced and prolonged her pets' lives, "I have personally experienced a miracle with my own dog and cat, both in renal failure."
- Others have also reported satisfaction with this product, usually combined with Epakitin (see above).
I heard but was unable to verify that the probiotics in Azodyl are a subset of those found in kefir, a cultured milk product similar to yogurt but with a wider variety of beneficial organisms, and that the manufacturers of Azodyl, when pressed, admitted that the product was derived from kefir. This suggests that feeding kefir might be beneficial for dogs with kidney disease, though Azodyl is probably a more concentrated source. Kefir is easy to make once you get the starter "grains," which look like little cauliflowers (this is not the same as a starter culture that is sometimes sold, but which is not self-propagating. The nutritional profile is very similar to yogurt. See Kefir Resources for more information on kefir.
There is also a custom yogurt starter culture that contains the three probiotics found in Azodyl plus Lactobacillus Bulgaricus (you would need to add your own psyllium).
There is a limited amount of evidence that soluble fiber helps to bind urea (the nitrogenous waste product that leads to elevated BUN). Both Azodyl (psyllium) and Epakitin (chitosan) contain soluble fiber. Other sources of soluble fiber include potatoes, sweet potatoes, winter squashes, broccoli, carrots, and apples. See On Squash, Fermentable Fiber and Feline Kidney Disease for more information.
Calcitriol is a relatively recent and somewhat controversial method for controlling calcium and phosphorus levels and hyperparathyroidism (high levels of the parathyroid hormone, or PTH, which is common with kidney disease). It is a form of vitamin D, and is the only Vitamin D form suitable for this treatment, because it has a very short half-life in the body. Calcitriol may enhance quality of life, particularly when hyperparathyroidism is present (which is common with kidney disease), even when it is started past the point where it can extend lifespan.
Calcitriol is most effective when phosphorus levels are normal (not above 6.0), though it may provide some benefit when levels are somewhat higher. It should only be used when calcium and phosphorus blood levels (measured in mg/dL) multiplied together do not exceed 60 to 75 (recommendations vary). Best results are obtained when phosphorus levels are no greater than 4.5, so aluminum-based phosphorus binders should be used to lower phosphorus values as needed (do not use calcium as a phosphorus binder when giving Calcitriol, though you should still add normal amounts of calcium to homemade diets).
Note that if calcium appears elevated, you can do an ionized calcium test to determine whether calcium is really elevated; if so, calcitriol should not be used. If both ionized calcium and phosphosphorus levels are normal, then you should be able to try Calcitriol. Two things that can be done to reduce calcium levels is to switch from Lactated Ringer's Solution (LRS) for sub-q fluids to Normosol or Sodium Chloride, and stop giving Epakitin or other calcium supplements (note you do need to add calcium to a homemade diet in order to balance out the amount of phosphorus in the diet; you just shouldn't add more to act as a phosphorus binder, use aluminum hydroxide powder instead).
Regular monitoring is needed when using this supplement to ensure that calcium and phosphorus levels in the blood remain within these limits. It's also a good idea to measure PTH (parathyroid hormone, which controls calcium and phosphorus levels in the blood), which is directly affected by calcitriol.
Prolonging Life and Kidney Function (Chew, DiBartola) indicates that calcitriol may be beneficial in dogs with chronic kidney disease:
"A salutary effect of calcitriol treatment of CRF was recently shown in a placebo-controlled study of 37 dogs. The dose of calcitriol was adjusted according to serial ionized calcium and PTH determinations, and ranged from 0.75 to 5.0 ng/kg/day. Over the course of 1 year, there was a significant reduction in mortality rate in the group of dogs receiving calcitriol (28%) as compared to the placebo group (63% mortality)." This article also has information on dosage levels, and suggests that intermittent rather than daily dosing may be preferable when using calcitriol.
Kirk's Current Veterinary Therapy IV has a chapter on calcitriol, and says:
"In a randomized controlled clinical trial, calcitriol was shown to prolong survival and forestall development of uremic crises in dogs with stage III [creatinine 2.1 - 5.0] and early stage IV CKD. Because the rate of progression of CKD was slower in dogs receiving calcitriol in this study, it was concluded that calcitriol favorable influenced clinical outcome as a consequence of providing a renoprotective effect."
Veterinary Partner has this description of Calcitriol in their article on Calcium Phosphorus Balance:
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.
A calcitriol study done by Dr. David Polzin concluded that " a daily low dose of calcitriol stabilized kidney function, slowed the progression of the disease and prolonged survival."
See the following for more information on the use of Calcitriol for dogs with kidney disease:
- Renal Secondary Hyperparathyroidism
- Calcitriol, the Good Guy of the 90's
- Managing a Renal Crisis
- 11 guidelines for conservatively treating chronic kidney disease (see item 11)
- Calcitriol for Cats & Dogs - Reference Page
- Calcitriol for Cats & Dogs - Reference Page
- Case Study of a dog with renal secondary hyperparathyroidism leading to swelling of the face (click on the Diagnosis link for more info, including treatment with Calcitriol).
It is very important for the dog to always have access to plenty of fresh water, whether or not you are giving fluids. Wet food (raw, cooked, canned, or water added to dry food) also helps them stay hydrated.
Fluids: Lactate Ringers Solution (LRS) is an electrolyte mix, and is the most common solution used, but if your dog has high potassium levels, then you may want to use just saline, and if your dog has high calcium level, you may need something else such as Normosol. Your vet will be able to advise you which fluids to use.
Amount and frequency: Standard maintenance dosage recommendations range from 5 to 15 ml per pound of body weight to 50 to 60 ml/kg (23 to 27 ml/lb) at one time. When giving amounts above 10 ml per pound, you may need to move the needle to a different spot to get them all in. The amount will vary depending on degree of dehydration and how much water your dog is drinking and getting in his food. Frequency of administering fluids will increase as the dog's condition worsens. My vet originally prescribed 800-1,000 ml two or three times a week for my 45 lb dog, but we eventually reduced that to 500 ml (just over 10 ml/lb), as she did better with this amount and didn't appear to need more.
Needles: Terumo 19 gauge thin wall needles have been recommended as the sharpest, most pain-free needles, and the thin wall allows a larger hole, which will reduce the amount of time it takes in infuse the fluids into the dog. However, when I switched to a standard 18 gauge needle, the fluids went in much more quickly, which made it easier on both the dog and me, and the needle caused no more problems than the smaller gauge had. Be sure to change around where you insert the needle so one spot doesn't get sore.
Warming the fluids is important in order to make the process more comfortable for the dog. This can be done with a large heating pad or in a bowl of hot water or in the microwave. Be certain that the fluids are not too hot, especially if you use a microwave. You want them to be close to body temperature.
Give treats or even feed a meal while your dog is getting fluids, to make the experience more pleasant.
Fluids are not recommended if your dog has heart problems or edema. Never give more fluids if prior fluids are not yet absorbed.
When we first gave fluids to my dog, I believe she did not need fluid therapy. However, when her water intake increased about threefold, I began giving fluids again. I think that you may be able to judge how much sub-q fluids are needed by how much water your dog is drinking. If your dog is drinking a great deal but has trouble absorbing fluids, this is a sign of low albumin (which can be the result of feeding too little protein), and should be discussed with your vet.
Implantable Catheter Set: There is a new option available for giving sub-q fluids, called the Endo-Sof Subcutaneous Catheter Set or GIF Tube. A catheter is placed in the dog using anesthetic. You then no longer have to stick the dog with a needle, you can just use the catheter port to give the fluids. It lasts up to one year before needing to be replaced. See Subcutaneous Fluids (scroll down to the bottom of the page) for more info. Note that several people have reported problems with the use of this catheter, including infections and clogging up. Before making a decision, I would advise joining the K9KidneyDiet group (they have information in their Files section and people who have used them can tell you about their experiences) and/or the GIF-Tube group for more information.
See the following for information on fluids and where to find supplies at a reasonable price (some of these sites are oriented towards cats, but the information is the same):
- Giving Subcutaneous Fluids to a Dog
- Administering Subcutaneous Fluids at Home
- Sophia gets her Subcutaneous (sub-Q) Fluids
- How to Give Sub-Cutaneous Fluids using a Giving Set
- Mail Order Supplies for Cats with Chronic Renal Failure (CRF)
- Fluids for CRF Felines - Buying Locally - Some Sources of Supply
- Thriving Pets
- HydroVet Fluid Administration Supplies
- Content of Common I.V. Solutions
- Valley Vet
One person said she was able to get fluids (LRS) at a good price from Costco. Apparently not all the stores carry it, so you may need to call around. You do not need to be a Costco member to use their pharmacy. Walmart, Target, Walgreens and other local pharmacies may also have good prices.
Here's a method that was described by one person for giving fluids more quickly:
Shannon Watts (pixxi78 @ yahoo.com), says, "I got it down to under 5 minutes using the following method (it uses more equipment so it is more expensive). In addition to the bag of fluids, tubing, and Terumo 20G x 1" needles, I also bought an additional piece of tubing, a 3-way stopcock, and a large 60cc syringe. Using your current setup, you attach the stopcock (instead of the needle) to the IV tubing coming from the fluid bag. Next, the syringe attaches to one spoke of the stopcock, and the extra tubing to the third spoke of the stopcock, and finally the needle at the end of the extra tubing. This way, I'd use the syringe to pull in 60cc of fluid, flip the stopcock and push the fluids in. It's very fast. To make it affordable, I only switched the tubing/stopcock/syringe about once a week." Note that it's important to maintain sterility, so ask your vet for help before trying to do this yourself.
Dogs on sub-q fluids, or who are simply drinking a lot of water due to kidney disease, are frequently incontinent. These products may help:
- Drs. Foster & Smith offer waterproof liners and pads in lots of different sizes and shapes that can be used to protect dog beds or furniture.
- Waterproof mattress pads sold for kids' beds may be a more affordable option.
- Discount Pet Pads offers both new and used washable underpads in different sizes.
- Petpads are "gently used." Composed of water-resistant material on one side and absorbent on the other.
- Many sites offer waterproof dog beds.
- I have used Changing Table Pads that I put under the bedding so the urine does not soak thru, and then just wash those and the bedding in the morning as needed.
- Sam's Club sells disposable pads such as Member's Mark® Comfort Shape® Underpads. and Disposable Underpads (also available in smaller size).
- Also see Stay At Home Protection Pads and Pooch Pads at KV Vet.
- Little Stinker Housebreaking Pads or similar items may also work.
- Poochie Pants cute diaper garments for male and female dogs of all sizes
- Pet Peepers Disposable Pet Diapers this site offers a variety of different diaper garments, including some that are washable.
- Ultimate Vet Fleece extremely soft and thick, this fleece lets liquids run thru so dog stays dry (waterproof liner of some kind needed underneath). The "super deluxe" is so thick that a 4x5 sheet will not fit in a regular-size washing machine.
See the section on Nursing Aids/Other for links to more info on commercial and homemade products for incontinence. I've also found that making sure she goes out last thing before bed, and letting her out once in the middle of the night on the days that she gets sub-q fluids, has greatly reduced the incidence of incontinence.
More helpful hints on dealing with incontinence on these sites (they're talking about paralyzed dogs, but many of the recommendations are also applicable to incontinence for other reasons):
Wonderpuppy.net -- see the sections on Bellybands, Diapers, Cleaning the dog and diaper rash, Floors, and Protecting your bed and furniture.
Paralyzed Dogs: How to Care for Them
Dog Diaper Comparison
Diapers and male wraps includes tips on skin care and how to make your own belly bands.
ACE inhibitors such as Benazepril (Lotensin, Fortekor) and Enalapril (Enacard) have been found helpful in people with kidney disease, and are being used with dogs and cats as well. They help prevent protein loss in the urine and control high blood pressure, which is common in dogs with kidney disease, and may slow the progression of the disease. Benazepril may be the better choice than enalapril for dogs with elevated creatinine, as it is partly eliminated via the liver rather than completely through the kidneys. See A Changing Role for ACE Inhibitors? for more information on this topic.
ACE inhibitors are primarily used for dogs with glomerulonephritis, where there is a significant urinary protein loss. A urine protein:creatine ratio, or UPC, can be used to measure the amount of protein in urine, as long as there is no infection present. A UPC of 2.0 or higher is classified as glomerulonephritis, but anything over 0.5 is considered abnormal in the absence of infection (which will distort results). See Urine protein to creatinine ratio for more information.
ACE inhibitors may also be beneficial if high blood pressure is involved, which is less common in dogs than it is in humans. For more information on both sides of the issue, see ACE Inhibitors and CRF Cats and Early Detection and Prevention of Progression of Renal Disease......A Role for ACE Inhibitors (which also talks about the role of phosphorus in renal disease). Also see High Blood Pressure for more info on this condition. Also see the Glomerulonephritis links of my site for more information.
Amlodipine besylate (Norvasc) and other calcium channel blockers (used to treat high blood pressure) will not help to reduce proteinuria, but can be combined with ACE inhibitors to further reduce blood pressure if needed. High blood pressure is also sometimes treated with aldosterone inhibitors, such as spironolactone. Low-dose aspirin (0.5-5 mg/kg twice a day) is also used for dogs with glomerulonephritis for its anti-inflammatory action and its effect on platelets (use aspirin only under guidance from your vet). See the human-oriented document, Management of Glomerular Proteinuria, for more information on controlling proteinuria.
When ACE inhibitors are used to treat heart disease, it is recommended to check creatinine and BUN within a few days of starting the drug to make sure the drug is not having an adverse effect on the kidneys. This may not be necessary for dogs with kidney disease, or mild increases in creatinine may be normal. See the following for more information:
When the glomerulus is leaking protein, less filtration means less urinary protein loss, which is good. If the kidney is failing or if the patient is very dehydrated, less filtration means less kidney function, which is bad. This makes ACE inhibitor use a bit tricky in heart failure patients where we do not want to treat the heart disease at the expense of the kidneys. For patients without heart failure, where you are treating high blood pressure or renal protein loss, the drop in kidney function that comes with ACE inhibitor use is not significant.
Fortekor® (Benazepril) from the manufacturer's website:
In contrast with other ACE Inhibitors, benazepril is excreted 54% via the biliary [liver] and 46% via the urinary [kidney] route in dogs . . . The clearance of benazepril is not affected in dogs or cats with impaired renal function and therefore no adjustment of FORTEKOR dose is required in either species in cases of renal insufficiency. . . .
Dogs: As is routine in cases of chronic renal insufficiency, it is recommended to monitor plasma urea and creatinine concentrations. No evidence of renal toxicity to Fortekor has been observed in dogs during clinical trials.
Cats: Fortekor may increase plasma creatinine concentrations at the start of therapy. This effect is related to the therapeutic effect of the product in reducing blood pressure, and therefore is not necessarily a reason to stop therapy in the absence of other signs.
Dosing and Safety from the manufacturer's website:
Studies have shown that, in both cats2 and dogs3,4 with renal compromise, there is no increased exposure to benazepril, therefore no dose adjustment of Fortekor is required. This is in contrast to enalapril maleate in dogs, where exposure to enalaprilat is increased in dogs with renal impairment.
Changes in creatinine: In patients with kidney disease, a small rise in creatinine is sometimes seen when treatment is first started, due to the therapeutic effect of Fortekor in reducing glomerular pressure. In humans, it has been shown that an acute increase in creatinine of up to 30% that stabilises within the first 2 months of therapy is associated with long-term preservation of renal function. A greater rise in creatinine should be investigated, as it could indicate deterioration in the underlying kidney disease, or an episode of decompensation or dehydration.
There is some indication that the prescription drug pentoxifylline may help to improve blood flow to the kidneys and reduce proteinuria. Pentoxifylline is considered a relatively safe drug and may be worth trying. See Pentoxifylline (Trental®) for more information on the drug and dosage for dogs. These sites have more information on studies done on humans with kidney disease, primarily when associated with diabetes
- Inexpensive Drug Improves Kidney Function in Diabetics
- The renoprotective potential of pentoxifylline in chronic kidney disease
- Pentoxifylline May Ameliorate Diabetic Renal Disease
- Pentoxifylline improves haemoglobin and interleukin-6 levels in chronic kidney disease
- 11 guidelines for conservatively treating chronic kidney disease (see items 9 and 10)
Dogs with kidney disease can have very acidic systems, called metabolic acidosis, which can contribute to gastrointestinal and even esophageal or mouth ulcers. The CO2 level in the blood work is what is used to determine acidity (low CO2 means acidic). Acidosis can result in muscle wasting, loss of lean body mass, bone disease, weakness (especially with exercise) and weight loss, although these can also be symptoms of too little protein in the diet, and of hypokalemia (low potassium). Although metabolic acidosis is easy to treat, it is often ignored.
- Sub-q fluids using Lactated Ringer's Solution (LRS) may be helpful.
- Baking soda (sodium bicarbonate) can be used to help neutralize the system, if your vet agrees. Sodium bicarbonate also can be used to treat hyperkalemia (high potassium). Note that sodium bicarbonate does not contribute to high blood pressure, so there's no need to worry about using it even if your dog is hypertensive. See Fanconi Disease Management for Veterinarians (item 7 under Management Dosing Guidelines and further down under Sodium Bicarbonate Dosing Calculator) for some additional info on treating with sodium bicarbonate tablets.
- Potassium Citrate can be used to treat hypokalemia (low potassium) and also to reduce metabolic acidosis (though the article on Fanconi Syndrome above says that it is not effective for that condition).
- The amino acid l-glutamine may help control metabolic acidosis.
See the following for more information on treatment of metabolic acidosis, including dosage levels for sodium bicarbonate and potassium citrate:
- 11 guidelines for conservatively treating chronic kidney disease (see item 5)
- Current Concepts for the Management of Chronic Renal Failure in the Dog and Cat
- Acid-Base, Electrolytes, and Renal Failure
Potassium levels are important and can affect the heart, so neither of these should be supplemented without your veterinarian's knowledge and consent. The first link above also has guidelines for treating hyperkalemia and hypokalemia (high and low potassium levels, see item 4).
H2 Blockers (antacids) can be used to help prevent ulcers, and Carafate (sucralfate) can be used to treat ulcers. H2 blockers used to treat uremic gastritis include Pepcid (famotidine) and Zantac (ranitidine), but Tagamet (cimetidine) is not recommended as it can alter the metabolism of other drugs. Carafate is protective and can help heal any existing ulcers (Tagamet and Pepcid do not help with healing, but can be combined with sucralfate to reduce pain). Give Carafate away from meals (at least one hour before or two hours after), and Pepcid or Zantac at a different time, such as half an hour before meals (half an hour after the Carafate) if used together. If you are not using Carafate, give the Tagamet or Pepcid two hours after eating. Signs of ulcers can include vomiting (particularly if you see blood or what looks like coffee grounds in it), diarrhea, and black or tarry stools (melena), but the absence of these signs does not rule out ulcers. Other signs may include loss of appetite, weight loss, increased salivation, and abdominal pain. Ulcers can cause regenerative anemia, possibly associated with iron deficiency, and increased BUN (with no comparable increase in creatinine). Natural treatments that may help with ulcers include slippery elm, raw honey and cabbage juice (just boil up some cabbage and then give the water it was boiled in). More information, including dosage amounts for the above medications:
- Current Concepts for the Management of Chronic Renal Failure in the Dog and Cat
- Gastric ulcer disease in dogs and cats (Proceedings)
It may be helpful to treat a dog with kidney disease prophylactically with something like Pepcid. Ulcers can develop even without metabolic acidosis. Starting the dog on Pepcid when kidney disease is first diagnosed, even without symptoms, may be beneficial in stopping ulceration from developing. WARNING: I had my dog on Pepcid for over a year when I discovered it was contributing to her inappetence. Once I stopped giving it, her appetite improved immediately. I have since heard a similar story from another person. If your dog has problems with inappetence and you are using this drug or something similar (Tagamet, Zantac, etc.), you may want to try stopping the drug to see if it helps.
Drugs that can help with inappetence due to nausea:
- Meclizine (Bonine, Antivert; more info here) can help with nausea. One dog with moderate to severe kidney disease started eating well after being picky for ages and gained over ten pounds after being put on this drug.
- Mirtazapine (Remeron) is an antidepressant that has strong anti-nausea properties and acts as a strong appetite stimulant.
- Ondansetron (Zofran) is a human chemotherapy drug that can be used to stop severe vomiting.
- Cerenia (maropitant citrate) is a new drug from Pfizer that controls nausea but is very expensive.
- Metoclopramide (Reglan) is used to control vomiting and increase gastric motility. It is eliminated by the kidney, so dosage may need to be reduced in dogs with kidney disease. If signs of overdose are seen, such as restlessness, lethargy, shaking, or muscle spasms, antihistamines such as Benadryl can help to counteract them.
- Promethazine (Phenergan) is an older, inexpensive medication that can help with nausea and vomiting. It is actually an antihistamine. Dosage is 1 mg/kg twice a day according to this site on Antihistamines.
There are also some herbal blends that can be used for nausea, such as Ginger-Mint from Animals' Apawthecary, Tasha's Ginger Tummy and Minty Ginger from Herbs for Kids (available at Whole Foods and other health food stores). You can also give ginger capsules or ginger tea. Some studies have found ginger to be as effective as metoclopramide for nausea and vomiting.
Iron supplements may also be helpful for anemia caused by kidney disease. Pet-Tinic seems to be the most commonly used, but Nutrived B Complex Plus Iron, which is similar, appears to be a little better. Too much iron can cause toxicity, however, so this should only be given with your vet's approval. Iron will only help if the anemia is regenerative, not non-regenerative, so ask your vet about that as well. Note that anemia can also be linked to a vitamin B12 (cobalamin) deficiency, and this vitamin should be safe to supplement, either by itself or as part of a B-complex supplement (or both).
The kidneys produce erythropoietin (EPO), a hormone that stimulates the bone marrow to make red blood cells. It is not uncommon for dogs with kidney disease to be anemic. Human erythropoietin supplements, including Epogen and Procrit, can be used with dogs, though there is a danger that they will cause antibodies to be produced, forcing the drug to be discontinued. A canine version (rcEPO) was produced and tested at Cornell Veterinary College, but is not commercially available.
Aranesp (darbepoetin alfa) is a supplement related to Epogen that is used to treat anemia related to kidney disease that has also been used for dogs. A human study found that Aranesp given every two weeks was as effective as Epogen given weekly. Aranesp is available from Thriving Pets.
You need to test erythropoietin levels to see if they're the cause of the low red blood cells, otherwise, the medication can be harmful. Anemia can also be caused by malnutrition if you are feeding too little protein.
Creating red blood cells requires iron, so iron supplementation is recommended while taking EPO or other medication designed to increase red blood cell production. Again, too much iron can be toxic, so follow your vet's dosage instructions.
See the following for more info:
- Erythropoietin (Epogen®, Procrit®)
- Erythropoietin (Epogen, Procrit) Patient Information Sheet
- Epogen Recall September 2010