To Gilbert from Ron Hines

The SDMA Kidney Test In Your Dog & Cat – What It Means – What It Doesn’t Mean 

  My Vet Says My Cat Or Dog Needs A Special Kidney Diet  

 RenalTech™ – The Mars / VCA Kidney Test Algorithm

 

  Aluminum Hydroxide For Kidney Failure?

Kidney Disease In Your Dog And Cat – Current Diagnosis And Treatment

There was a time when infectious diseases were the leading cause of mortality in our dogs and cats. We have good, long-lasting vaccines now so those times have passed. Today, chronic kidney disease leading to kidney failure is near the top of the list as the cause of death in older pets. Just behind the #1 and #2 causes in dogs – cancer and heart disease – and probably ahead of heart disease in cats.

Not every pet with kidney disease has age-related kidney decline. A few dogs carry genetic defects that cause their kidneys to fail at about 1-3 years of age. The kidneys of cats that inherited polycystic kidney disease often fail in midlife ( read here )  A tendency to form kidney stones can also destroy the kidneys. ( read here & here)  So can exposure to dietary toxins (eg antifreeze, mold aflatoxins).  In others, unfortunate reactions to medications are to blame and, in a few, autoimmune disorders. ( read here ), and perhaps in some, infectious organisms like leptospirosis.   ( read here & here)

But for the vast majority of our pets, kidney failure is a disease of old age. By the time a dog reaches ten, about 15% show laboratory test evidence that their kidneys have lost some of their capacity to cleanse their body. In 10-year-old cats, those chances are even higher. By the time house cats reach the age of 15, most of them have some decline in their kidney function. Vets used to just call this progressive glomerulosclerosis. Today we call it CKD (chronic kidney disease = CRD = chronic renal  disease = chronic tubulointerstitial nephritis). All are synonyms for the slow, relentless, age-related inflammation that gradually destroys a pet’s individual kidney filter units, the nephrons. You might notice that the less doctors understand about a specific health problem that frustrates them, the more complicated multiple names they tend to give it.

Old age brings multiple health issues to all of us. But only some of our cats and dogs will reach the point of actual kidney failure. For many, unrelated heath issues will cause them to eventually pass away. (read here)    Organs of your dog or cat’s body have to work in unison to keep each other functioning well. So although you may have been told that your pet died of heart failure, or perhaps and infection, its kidney issues may have contributed to its demise. (read here& here)    

The Merck veterinary manual states that chronic kidney disease (CKD) affects as many as 10% of dogs and 35% of cats during their lifetimes. That is probably a major underestimate. In dogs and cats that are fortunate enough to reach old age, the percentage with the problem is considerably larger.  God generously gave all mammals considerably more of those nephron filter units that required. Us humans have about 1 million nephron filter units in each of our kidneys. ( read here ) No one I know of has estimated their number in dogs or cats.  With every heartbeat, about 20-25% of your dog and cat’s heart volume of blood is sent through your pet’s kidneys for cleansing, fluid regulation and blood ion adjustments.

Do Veterinarians Know Much More About Why The Kidneys Of Elderly Cats And Dogs Fail Than They Did 10 Years Ago?

Not really.

Why it is that the kidneys of old dogs and old cats commonly fail remains unknown. There are oodles of theories. All remain unproven. Veterinarians do not know if there is one major cause or many causes. We also know very little about the dynamic events (real time processes) occurring in a pet’s kidneys that lead to their eventual failure. What we do know is that by the time kidneys fail, they all look pretty much the same when viewed under a microscope. The glomeruli (the numerous small filters that clean the blood) are scarred to the point that they no longer work and there is usually evidence of inflammation surrounding them. The term for that scarring is glomerulosclerosis. Microscopically it is unmistakable. It is irreversible and pathologists viewing those slides call them no more than the end stage wreckage of what were once healthy kidneys.

Unfortunately, much of what you will read online is an echo chamber of supposition, guesswork and consensus statements based on data taken from conflicting human, rat, mouse, dog and cat kidney-decline studies. Since veterinarians have little idea why kidney decline occurs in older pets, it is quite difficult for them to plan strategies to treat, slow or prevent the disease. That goes for all the medications, lifestyle changes and diets that your veterinarian hopes might slow the progression of CKD. It is one of the least understood areas of veterinary medicine.

The only studies that pass scientific muster were run years ago – mostly in dogs but one in cats. Studies that would confirm those results in cats and dogs or look for effective medications can no longer be performed in the Western world. They involved removing the majority of an animal’s kidneys and would be considered too cruel to perform today.  Most current veterinary studies don’t pass muster because they have too many multiple confounding variables to make much sense of the results (read here) or too few animals to support the conclusions (be statistically valid) that were reached. In addition, companies with products to sell you underwrite the costs of most of them – never a good situation for unbiased conclusions.   

I’m left in that same data bind. That’s why I procrastinated for 5 years before writing this article, and the ones on the SDMA test and the effectiveness of veterinary Kidney Diets. Published results are all over the map. Most were never repeated and none were independently verified. When Science collides with the opportunity to make money, Science is rarely the winner. ( read here ) Its not that money is not out there to run well-designed studies. Colgate-Palmolive, the parent company of Hills Prescription diets, had 2019 revenues of ~15.7 Billion dollars with ~1.7 billion spent on advertising and zero on neutral nutritional inquiry. Idexx anticipates 2020 revenues to be ~2.6 billion. But these industries never toss the dice when uncertain outcomes are possible.

So I had to bone up on what physicians have learned about diagnosing and treating CKD in their patients. Some are going to say the same thing I mentioned earlier: that one cannot trust that what works or doesn’t work in humans will work or not work in your dog or cat.  That, to some extent, is true. But it’s the best I can offer you. Human medical research is not free of shenanigans either; but the FDA and the NIH attempt to see that there is less of it. The veterinary International Renal Interest Society (IRIS) periodically put out kidney disease treatment guidelines for dogs and cats. These guidelines are produced by specialists that have devoted their lives to attempting to understand kidney disease in dogs and cats. Unfortunately, suggested time points when medications need to begin, which ones are likely to help, which don’t and at what dose they should be used are speculative due to the lack of credible research. The same goes for their nutritional suggestions.  

If My Dog Or Cat Has Kidney Disease What Signs Might I See?

The most common forms of kidney disease in dogs and cats take years to develop. During the earliest stages, you are unlikely to notice any changes in your cat or dog’s behavior or appearance. That is because, as I mentioned earlier, the kidneys of dogs, cats and humans have large, built-in reserves – many more individual filtering units (=nephrons) than are required to cleanse the blood.

That early period is when your pet’s bloodwork results (“wellness exams”, geriatric profiles) give your vet very little evidence that something is brewing. Cut-off values for normal blood results are somewhat arbitrary. High-end normals can be just that – normal for your pet. They can also return to midline values the following day.  But high-end “normal” values (particularly when they persist) can indicate a brewing problem. Few owners are going to repeat these tests every month to detect these trends. IRIS, the National Renal Interest Society, associates blood creatinine levels of 1.4 – 2.0 mg/dL for dogs and 1.6 – 2.8 for cats with this early period. The pet’s early morning urine might be a bit too dilute as well (low urine specific gravity Your pet’s early morning urine is generally as concentrated as it will be during that day) . Albumin protein leaking into your pet’s urine might be beginning warning as well. If the SDMA test is specific enough to allow your vet to confirm CKD earlier remains to be seen. Read about the Idexx patented SDMA test here .

A persistent increase in drinking and peeing (=polydipsia and polyuria =PD/PU) in your dog or cat in the absence of another explanation (eg  fever , diet change, hot weather, corticosteroids, diabetes, etc.) is often the earliest sign of kidney issues that pet owners tell me about. Or they might just say that they have notice that their pet is having more household ‘bathroom” accidents or that their cat’s litter box odor is stronger. As I mentioned, the urine that these pets produce is very dilute (low specific gravity). That is because you pet’s body is running more fluid through its kidneys in an attempt to keep blood waste products and toxin levels down. You can limit your dog and cat’s access to water during an 8-hour night, but never ever deprive these pets of all the water they care to drink in a 24 hour period.

The next thing you might notice in your cat or dog is less energy, less curiosity and more sleep time. That often occurs along with decreased appetite and picky eating that results in a drop in your pet’s body weight. Owners are often surprised when I point out how much weight their pet has lost. They often reply that they just thought it just comes with getting old. As CKD progresses, decreased appetite causes almost all pets loose lean body weight, not just fat. We are uncertain why dogs with advanced kidney disease loose their appetite, but it is almost certainly due in part to rising levels of metabolic wastes and toxins within their bodies (in doctorspeak: multifactorial metabolic derangements).  In us humans, the loss of lean muscle mass to CKD is one of the cardinal (best) indicators of approaching mortality. (read here) Elanco has two products on the market that attempt to increase appetite, Entyce® and Elura®. Read about those medications here.

Early kidney problems can be mistaken for a lot of things I already mentioned. Cognitive decline ( CDS aka dogie Alzheimer’s) is another. So its always a good idea to as your veterinarian to run a blood chemistry panel when you dogs and cats face memory issues. CKD and CDS can  and often do coexist together. Some associate the weakness that comes with advancing kidney disease as due to low blood potassium levels (=hypokalema). Although that sometimes does occur, it is only a small part of the problem. (ACE-inhibiting blood pressure medicines  like benazepril/enalapril and ARBs can actually cause potassium levels to be above normal = hyperkalemia).

A decrease in grooming activity – particularly in cats – can be another early sign of CKD. But everything from arthritis to chronic pain to triaditis and lymphoma can also be responsible for that unkempt look.

As CKD progresses, some dogs and cats begin to gag or vomit.  We have no way to determine for sure if those pets experience nausea as humans do – but many folks attribute the vomiting and gagging that is sometimes seen as CKD advances to that. Maropitant  (Cerenia®)  is not approved for long term use, but veterinarians have experience giving it for more extended periods to cats. (read here) Other veterinarians rely on metoclopramide (Reglan®). Although the long term use of metoclopramide has been associated with movement disorders in humans, none have been reported in dogs and cats. (read here) When given for more than a day or two one needs to be on the lookout for reduced intestinal motility and constipation. Other veterinarians attribute the vomiting of dogs and cats with CKD to stomach irritation (gastritis) caused by the uremic toxins and/or alterations in your pets body acidity (acid base balance). In advanced CKD cases, oral ulcers might occur as well.

It is common for dogs and cats with CKD to have gum (periodontal) disease. That needs to be tended to by your veterinarian – preferably in a low-risk manner (remember, these pets are poor anesthetic risks). ( read here ) Whether periodontal disease is the cause or result of kidney failure is still being debated. But we do know that in CKD, kidneys of dogs and cats can no longer keep blood phosphorus levels in check. High body phosphorus levels in your pet leads to loss of bone calcium (= secondary renal hyperparathyroidism ). That, in turn, leads to loose teeth and periodontal disease. ( read here )

CKD is a progressive disease. As it progresses, pets often become anemic. The build up of toxic waste products in their blood might explain a part of your pet’s lack of energy – but anemia – causing a lack of  energy certainly does as well. You pet’s kidneys have multiple chores. Besides cleansing its blood, normal kidneys produce most of its EPO (erythropoietin). EPO is essential for a pet’s bone marrow to produce red blood cells. Kidney disease often lowers a pet’s ability to produce it (some continues to be produced in the liver).  Picky eating also leads to malnutrition. That in itself can cause anemia – particularly if folic acid, vitamin B-12 and iron are not absorbed in sufficient quantities. Although marked anemia causes paleness and a rapid pulse, the color of your pet’s tongue or its heart rate at a veterinary hospital are not a good judge of anemia. A PCV or  RBC count test is.

Anything that causes blood loss can cause anemia (eg bleeding, parasites). Your veterinarian has learned to look for clues that hint to the underlying cause. When bleeding or parasites are the cause, examinations show that your pet’s bone marrow is cranking out new red blood cells as fast as it can (a regenerative anemia). The anemia associated with CKD is non-regenerative. Your pet’s bone marrow is neglecting the red blood cell formation process. ( read here & here)  The same bone marrow processes suppressed by CKD can lower a pet’s ability to generate thrombocyte as well. As in people,  thrombocytes (=blood platelets) play an important role in your pet’s blood clotting process.  ( read here ) That needs to be considered before any surgery or biopsy procedure is contemplated.

Multiple health issues often come into play as your pet ages. Heart valve issues, periodontal (gum) disease, digestive tract issues and liver issues are common in geriatric dogs and cats. These issue can all exist alongside each other and interplay with its kidney issues. So it can be quite hard for your veterinarian to sort out how much each issue is contributing to the symptoms you see. It sometimes also occurs that a medication helpful for one of those issues is contraindicated in another of the issues. Many pet owners don’t realize how many factors their veterinarian has to contemplate in making decisions. So second-guessing your vet (such as taking control of your pet’s treatment based on articles like this one) is perilous.

There are many other possible non-kidney causes for the signs and symptoms I just listed. Poor diet, heavy flea or tick infestations, blood parasites, adrenal gland disease and a host of other issues could explain them as well. A thorough veterinary exam and blood and urine tests should help sort them out. The simplest is your vet detecting smaller than normal, hard, lumpy kidneys on his/her physical exam. In fat pets, an x-ray or ultrasound might be required to visualize the pet’s kidneys.

The Royal Veterinary College in London reviewed their data base on 107,214 dogs treated at  British veterinary hospital over a 2-year period. They made some interesting discoveries: Among dogs diagnosed with CKD, those 12 yrs or older had 5.5 times the chance of having CKD than those between 4-7 yrs. Cocker Spaniels and Cavalier King Charles Spaniels had highest increased odds for developing CKD when compared to mutts. The most frequent signs that brought CKD dogs in for their initial examinations were vomiting, increased drinking/urination/incontinence, loss of appetite and loss of weight. Halitosis (periodontal disease) vomiting, diarrhea and lethargy were also among initial complaints. The median survival time from CKD diagnosis was 226 days (read here)

  

What Tests Will My Veterinarian Run?

The most important tests veterinarians use to detect kidney disease are your dog or cat’s blood creatinine and blood urea nitrogen levels, the specific gravity of your pet’s urine and the presence of albumen in your pet’s urine. After Idexx patented their SDMA blood test, they began an intensive marketing campaign suggesting that  SDMA levels detected kidney problems at an earlier stage than BUN and creatinine did. I find the test quite unreliable because too many non-kidney health issues have the ability to influence the test’s results. Read about that here. It is true that the blood creatinine test is not perfect, but it is still the best in-office blood gauge of kidney health that physicians and veterinarians have to offer.  

Your Pet’s Blood Creatinine Level

Creatinine is a normal byproduct of your pet’s metabolism – a waste product primarily created by normally functioning muscles (although the meat your pet consumes is also a source of some creatinine). It is not the same thing as the creatine that body builders eat. Vigorous exercise can also cause minor increases in your pet’s blood creatinine levels and dehydration (such as from vomiting or diarrhea) will also raise its creatinine levels.  Muscular large dogs also tend to have a bit higher blood creatinine levels. Certain commonly used antibiotics (such as Clavamox®/Augmentin®) and antacids (such as famotidine and ranitidine) have been known to elevate blood creatinine levels as well. (read here) There is also recent evidence that the doses of that antibiotic need to be lowered in advanced kidney disease in cats. ( read here ) azotemicuremic

When your pet’s kidneys are functioning properly, they collect creatinine from its blood and deposit it in its urine for elimination. When blood flow through your pet’s kidneys is decreased, or when the kidney’s tiny filters (glomeruli/nephrons) are damaged, creatinine will build up in your pet’s blood stream. I mentioned earlier that a pet’s normal kidneys have a reserve – a backup supply of filtering units. Its only when these reserves have been used up, as in CKD, that blood creatinine levels will begin to rise.  A mild-to-moderate elevation in your pet’s creatinine results mean the most when the same pet’s creatinine level has been monitored periodically over several years, or when other tests such as urine microalbuminuria or a drop in your dog’s early morning urine specific gravity (=a more dilute urine) confirm that kidney issues may be brewing. The test faces similar issues in cats. (read here )  When periodic monitoring consistently determines your pet’s creatinine levels to be in the “high end normal” range (i.e., 1.4 mg/dl for dogs and 1.6 in cats) , I would still be suspicious that a kidney problem is in its early stages (IRIS Stage 1).

I believe that the sensitivity and significance of the creatinine test could be improved if testing laboratories factored in breed, age, sex and body weight when reporting back if a creatinine test should be considered high, normal or low for a pet. But to the best of my knowledge, national testing laboratories like Antech or Idexx still do not do that. A perceptive veterinary nephrologist recently told me that, in her opinion, the testing lab’s creatinine “normals” were too narrow for large dogs and too wide for small ones. She gave, as an example, that in a Yorkie, a creatinine level of 1.2 mg/dl (=110µmol/L) might be a warning sign of potential kidney issues; whereas a reading of 2 mg/dl (=176.8µmol/L) in a 60-100 pound dog would probably be acceptable.

Many pet owners (and some veterinarians) are under the impression that its the elevation of creatinine and urea (BUN) in pets with CKD that makes pets ill. Actually, they are probably some of the least toxic of the 90+ known products that build up in the bloodstream when your pet’s kidneys fail (uremic toxins). ( read here & here )   Creatinine and urea are just primarily markers for the rest – like smoke is to fire.

Your Pet’s BUN  – Blood Urea Nitrogen Level

The amount of urea nitrogen (BUN) present in your pet’s blood can also be an indicator of its kidney health. However, BUN is more subject to changes (fluctuations)  that are not due to kidney disease than blood creatinine. That is because many other factors contribute to the rise or fall in the amount of urea nitrogen in your dog and cat’s blood:  infection, fever, stress, poor appetite, starvation. Cushing’s disease, intestinal bleeding, dehydration, extensive skin trauma, certain medications such as corticosteroids,  the amount of natural cortisol steroid in you pet’s blood, liver disease, congestive heart failure , ketoacidosis  and the degree of kidney BUN reabsorption occurring in your pet’s kidneys all have influences on its BUN level.

Like creatinine, urea nitrogen comes from the rearrangement and breakdown of proteins in your pet’s body (particularly those that occur in the liver – a vast rearrangement factory). The proteins present in your pet’s diet also contribute to its blood BUN level. BUN is still a very valuable test since two alarm bells are more likely to be noticed than one. There are still human nephrologists (kidney doctors) who feel that their patient’s  BUN level is a better predictor of approaching mortality than creatinine. (read here)

Tests To Detect Protein Leaking Into Your Pet’s Urine

Those little filtering units, the nephrons, that I mentioned earlier – the ones that are loosing their abilities in CKD – contain a critical group of cells. They are called podocytes. You can see some in the composite electron microscope images above. These critters cling to and line the small passages (arterioles) through which blood rushes within the kidney filters. Remember, I mentioned that your pet’s heart send  ~ 20-25% of its blood through the kidneys with every beat. Blood is also at one of its highest pressures when it courses through those channels. Podocytes have multiple projections or feet. (foot=podo+cyte=cell). Podocytes arrange themselves to have small slits between these feet (think of them more as fingers). Processes going on within the feet and the small gaps between them normally allow water, salts, and sugars to pass through the slits and out into the urine. When they are healthy, these cells do not allow blood proteins, lipids and blood cells to pass. These cells can vary the size of the slits between them and thus control urine volume as well. They seem to be the ultimate determinants of kidney health. ( read here ) It is only recently that scientists have become aware of how important podocytes are. The details are still being worked out. (read here) Everyone’s dream is to figured out a way to regenerate them. (read here)  When podocytes loose their grip on the tiny incoming blood filtering vessels that they cling to (the afferent glomerular arteriole capillaries), they end up in the urine. (read here) One way your veterinarian can get a measure of your dog and cat’s kidney health is by measuring the amount of  protein (mostly blood albumin) that is slipped past those cells and escaped into its urine. There are other ways protein can get into your pet’s urine. Protein is a content of all cells. So anything that damages the lining of your dog or cat’s urinary tract will release protein into its urine too. There are several ways for your veterinarian to detect protein in urine. Some are considerably more accurate than others:

There are relatively inexpensive paper dipstick strips – like the ones in the photo above – that will alert your veterinarian that there is protein in your pet’s urine specimen. But one cannot rely heavily on their accuracy when they are positive for protein.  (read here & here) What these strips can do is to alert your veterinarian that more sophisticated testing is required. The Urine P:C test and the urine microalbuminuria test are two tests considerably more accurate in identifying excessive amounts of urine protein. When accessing the source of the leakage, the presence of excessive albumin protein often points to leaking kidney filters. 

Your Pet’s Urine Protein to Creatinine Ratio aka UPCR, Urine P:C Ratio

The UPCR test compares the amount of protein found in your pet’s urine to the amount of creatinine found in the urine specimen. That adjusts for the fact that your pet’s urine can be very dilute or very concentrated at different points in the day and in different situations. Naturally, the more dilute the specimen is, the less protein will be in it and measuring the urine creatinine content adjusts for that. One study in 2005 appeared to show that dogs with higher UPCR ratios tended to live shorter lives than those with lower ratios. (read here) The UPCR test is also the preferred urine protein test choice for many human nephrologists. Although this is a very important test in identifying early cases of CKD in which the blood levels of creatinine and BUN have not yet increased or are borderline, there are other reasons the test might be positive. Fever, heavy exercise, generalized inflammations, blood in the urine, seizures and various forms of stress occasionally caused urine protein and creatinine levels to rise as well. Your vet will sort that out or, perhaps, confirm the results with a second UPCR test. The same caution pertains to the next option, a urine microalbuminuria test. Although there are animal hospitals  that run these tests in house, I send them out to a central lab like VCA’s Antech or TVMDL.  There are also more sophisticated dipsticks (eg Multistix PRO 10LS®) that can be read in-house on automated strip readers for more accurate results than just visually comparing the strip color changes (eg Clinitek Status® machine). Although they measure all urine protein, not just albumen, some claim they are just as accurate. (read here )  I have no experience using them.

The Urine Microalbuminuria Test

Since normal kidneys allow very little albumin protein in your pet’s blood to escape into its urine, there are tests that check for its increased presence without comparing it to the amount of creatinine that is present. As with the UPCR test above, non-kidney issues can also influence results. Some simply refer to this test as an albuminuria test. If I desired this test, I would send it out to a central lab as well. But if one wanted to to run them in a veterinary hospital (or at home) there are special albumin-specific urine dipsticks, which have a lower detection threshold than standard urine dipsticks. An albumin level above the upper limit is called microalbuminuria or just albuminuria. The cautions on interpretation of the results are the same as the urine protein-to-creatinine ratio/UPCR test. Some claim that albumin’s presence in elevated amounts in either test will pick up an impending kidney problem earlier than an abnormal blood creatinine test.  I do not know if that is true.  But when either urine protein test is elevated, a complete urinalysis, blood pressure determination, checking for heart or inflammatory diseases, diabetes, or hyperthyroidism (in cats) etc. might be in order for your pet. 

The Phosphorus Level In Your Pet’s Blood – A Very Good Indication Of The Seriousness Of The Problem

There is naturally a lot of phosphorus (in the form of phosphates) in your pet’ body. Next to calcium, it’s the most abundant mineral there. But most of it (~80%) is in your pet’s bones, not its blood. ( read here )  Phosphorus moves in and out of bone through the blood stream because it is an essential ingredient in all living body cells. When there is too much phosphorus present in your pet’s blood, it is the kidneys job to excrete it into the urine to keep things in balance (homeostasis). Normal kidneys cross-talk with bones in deciding how much phosphorus needs to be excreted into the urine. They do so through a circulating messenger protein produced in the bone, FGF23. FGF23 works in consort with kidney-produced vitamin D and the pet’s parathyroid glands – small glands in your pets neck – to keep phosphorus and calcium at optimum levels. This phosphorus regulation process begins to break down when too many of your dog or cat’s kidney filtering units, the nephrons, have been lost to CKD. At that point, the phosphorus level in your pet’s blood becomes abnormally high (hyperphosphatemia) and calcium is leached from the animal’s bones. Veterinarians believe that high blood phosphorus levels play a significant part in much of the health issues faced by cats and dogs with advanced CKD.  Although phosphorus levels occasionally begin to rise in the early stages of CKD, usually P levels go up in tandem with the other tests I mentioned earlier as the severity of the disease progresses. Higher than normal serum phosphorus levels are often seen in healthy young, growing puppies and kittens. That is normal.

The Diluteness Of Your Pet’s Urine – The Urine’s Specific Gravity

The refractometer in the photo above is a simple optical device. It will tell your veterinarian the specific gravity (SG or SpGr) of your pet’s urine. That is, the percentage of the sample that is pure water in relation to the other dissolved elements it contains. The lower the number, the closer the urine is to pure water. The reading varies throughout the day depending on the amount of water your pet consumes or any dehydration it experiences. The first urine of the morning is often the most concentrated and gives your vet an indication of the pet’s maximum kidney urine concentrating ability. 

Cats and dogs with progressive kidney disease gradually loose their ability to produce concentrated urine. It no longer has the intense color (and odor) that it once had. That is because to make up for their reduced ability to cleanse their bodies, these pets drink larger amounts of water to take maximum advantage of whatever normal kidney tissue remains. Dogs and cats with health kidneys should be able to produce urine with a specific gravity of at least 1.015 and 1.035 respectively. There are health problems other than kidney disease that can cause your pet to have increased amounts of dilute urine (polyuria)  and have excessive thirst (polydipsia). But persistently low specific gravity urine in a pet is always a cause for concern and an indication that further tests are needed to determine the underlying cause. It is probably unwise to compare the results obtained with one refractometer to results obtained from another. 

In us humans, a moderate decrease in urine specific gravity is considered part of the normal aging process (getting old). By age 40 the average blood flow through our kidneys then decreases by about 10% per decade. In one study, by age 85, roughly half of our glomeruli had lost their urine-concentrating abilities. ( read here  )  No animal studies exist but I do not suppose it is much different in our dogs and cats.

A Measurement Of Your Pet’s Blood Pressure

If veterinarians could get accurate indications of what your dog or cat’s true blood pressure was during its daily activities at home, that information would be extremely helpful in designing an individualized plan to slow CKD. It would also be a boon for evaluating the effectiveness of medications and diet changes as time went by. But there are only a few dogs (and even fewer cats) that remain relaxed in a veterinary hospital setting. Although pets may not show it, most are hyper-alert and apprehensive in strange settings. A pet owner’s apprehensiveness and worry is quickly sensed by your dog and cat too. No one has really found a successful way around that – although suggestions abound. To a much much lesser extent, it is the same with people – the “white coat effect” . (read here)  The second problem is there is considerable disagreement as to what a “normal” blood pressure reading is in dogs and cats. When it comes to dogs, there is no other animal on the planet that varies so much in size, anatomy, physiology and temperament. That’s due to our tinkering with their genetics. Read more about the difficulties in obtaining meaningful blood pressure readings in your cat and dog hereand here

When you go to your doctor, the nurse has a relatively easy time taking your systolic and diastolic (the lower number) blood pressure. Veterinarians rely on only your pet’s systolic blood pressure (the higher number) – machines in common use today in pets cannot accurately determine the lower number. Most veterinarians and physicians believe that higher than normal blood pressure is damaging to kidneys. That seems intuitively true and many studies have associated increased blood pressure with CKD. ( read here & here )  In one study, bringing abnormally high blood pressure down with medications appeared to decrease kidney protein leakage. ( read here ) A hopeful sign for kidney health. Research scientists also believe that high blood pressure and CKD are a two-way street. Not only does persistent high blood pressure injure the kidneys and hasten CKD; but CKD in itself is capable of causing high blood pressure through the release of renin.   Whatever the dynamics of CKD in your pet, high blood pressure is an undesirable thing. One study I know of did not find an association between elevated blood pressure and the extent of kidney damage (in cats). (read here )

Kidney Biopsies

Kidney biopsies (a snippet of tissue taken laparoscopically or surgically)  might tell your vet more about what undesirable processes are occurring in an individual pet’s kidneys. But kidney biopsies are both somewhat dangerous and expensive and when the report comes back as “garden variety” glomerulosclerosis, your pet’s treatment options are not enhanced. Kidney biopsies are best reserved for situations where other results do not add up. For instance, an enlarged kidney that might be cancerous. Or kidney failure in a young dog or cat. A biopsy might also be of value to a dog or cat breeder interested in knowing why they have an unusually high incidence of kidney disease in their bloodlines.

The SDMA Test

The SDMA test is the newest test of kidney health available to your veterinarian. In 2018, it is commercially available only through Idexx Laboratories. That is because they patented the test procedure in 2013. There is little doubt in my mind that SDMA levels rise in pets with kidney disease and there is certainly no harm in running this test. But whether elevated test results are specific only to kidney disease or give your vet more or earlier option to delay the progress of CKD remains highly speculative. By the time you read this article, I may have had time to write an article specifically on the benefits and drawbacks of the SDMA test. I am tracking the results in a number of dogs and cats and would be pleased to add data from your pet as well. The more animals I can match with histories and outcomes, the more accurate the article will be. If have already begun an article on the flaws and deficiencies in the SDMA test, you can read it hereThe National Kidney Foundation is a major advocate for people with CKD. It publishes a journal, the American Journal of Kidney Disease, and has a Guidestar rating of gold (the same as the Boy Scouts). Last year, I wrote an email to a Tufts nephrologists on the NKF scientific advisory board. I  asked her why the SDMA test was not recommended as key prognosticator for people with CKD – if it was so desirable in our pets. This was her reply: It is nice to meet you, even if by email. SDMA has some rather weak data as a GFR measurement method in humans. We actually re-looked at this data again to see if we should investigate it further and confirmed our interpretation that the data are quite poor. L

The Simple Test That Always Tells The Truth

When I was a teenager, I worked as an assistant to a veterinarian in Brownsville, Texas. Dr. Phillips palpated the kidneys of every dog and cat that came through the door. When dogs and cats came in with small, hard, lumpy kidneys he knew they had kidney issues and told me so. In advanced CKD, the kidneys are firm due to hard scar tissue and shrunken and lumpy due to loss of their nephron filtering units. Palpation can be a challenge in overweight pets and those that do not appreciate being poked or touched.  Those will need ultrasound imaging or x-rays to detect those changes.

As Time Goes By, What Are The Most  Important Things I Need To Monitor In My Dog And Cat With CKD?

Your pet’s body weight is something you can monitor at home. In studies of dogs, cats, underweight pets had significantly shorter survival times once CKD was diagnosed. In some cases (in cats), that weight loss preceded negative changes in their bloodwork. (read here & here) In humans, obesity has a negative impact on kidney health. So in people, they look at lean muscle mass, not body weight, in monitoring the kidneys because obesity is a known danger for CKD progression. One study found the same trend in dogs. (read here)   Commercial “renal diets” tend to substitute fat for protein. So in deciding if they are helpful, you need to be sure it is not just fat that your pet is putting on. But looking back at the outcomes of dogs and cats that had kidney issues that I’ve seen over the years – I’ll take a fat one over a thin one any day.

In advanced cases of CKD, anemia – measured through a simple in-office PCV blood test – is a quite accurate measure of the advance of CKD. In earlier stages of the disease, checking a drop of early-morning urine for its specific gravity is a simple, easily-performed, home test as well.

All the other tests I mentioned earlier add data too. But please do not put much faith in the meaning of relatively minor fluctuations that occur in any of them. Like you, I’m always happier to see them go down or remain relatively flat than go up. But tracking them too frequently, obsessing over them or trying to make too much out of individual results leads pet owners (and veterinarians) to needless worry. You are looking for trends.

What Are The Treatment Options For My Cat And Dog?

Medications And Diet To Maintain You Dog Or Cat’s Normal Phosphorus Level

High blood phosphorus levels seem destructive to pets with CKD. We have no hard evidence that phosphorus (in the form of phosphate) causes kidney disease in dogs and cats, but as CKD progresses, their blood phosphorus levels tend to go up. (read here) Human physician have similar suspicions. Sugar cane workers in the tropics develop CKD at an abnormally high rate. One theory is that the intense heat in which they work causes recurrent dehydration which injures their kidneys. To compound that, they quench their enormous thirst with high-phosphate soft drinks. 

Oral Phosphate Binders

The average humans, diet is thought to contain about 2-3 times the amount of phosphorus the body requires. The average human intake is 1000-1300 mg/day. I do not know what a pet’s average intake is, perhaps that data exists. But most veterinary nutritionists believe that dogs and cats can do quite well on considerably less phosphorus than they are probably getting in common diets.  As CKD progresses, an intestinal phosphorus binder that lessens the absorption of the phosphorus in your pet’s food is often required in addition to a low phosphorus diet to keep the pet’s blood phosphorus level at its lower normal limit. They work best when given with, just before, or just after a meal. There are a lot of phosphate binders on the market. They all make much of the phosphorus in the diet insoluble so that it cannot leave the intestine. It passes out in the pets stools. Some, like Maalox® and Basaljel (aluminum carbonate) contain aluminum and occasionally cause constipation. Although there is some apprehension that ingesting the aluminum they contain on a regular basis might not be a good idea, they are still in common veterinary and human use. Do not give them at the same time you give you pet other medications because they may interfere with the other drug’s absorption. Others binders contain calcium carbonate (like Tums®). With those, one must be sure blood calcium levels do not become too high. Products like Epakitin® (Vetquinol) and Pronefra® (Virbac Corp.) contain, in addition to calcium carbonate, crab and/or shrimp shells (chitin & chitosan). Studies on Pronefra®’s taste preference were generated by the makers, Virbac. Naturally, their’s came out the winner.  (read here)

Renalzin®(Lanthanum Carbonate) is another option.  It contains no aluminum or calcium. Another advantage of this drug is that it is available as a tasteless liquid. (many cats in particular do not like the taste of phosphorus binders) In 2007, the EFSA approved its use (Lantharenol® Bayer) as an additive to be placed in an adult cat’s food to decrease intestinal phosphate absorption. (read here) More sophisticated phosphate binders are in use in humans with CKD – resin binders like Sevelamer (Renagel® & Renvela® ) that do not contain calcium or aluminum either. You can read what limited data we have on their use in dogs and cats here. Some are known to interfere with the absorption of fat soluble vitamins (like vitamin D/calcitriol). ( read here ) Whichever product you use, be sure its use does not keep you pet from meeting its nutritional needs (no turning up its nose at its food).

 A Diet Change

Initially, a diet change alone might be sufficient to keep your pet’ blood phosphorus levels within normal values. And there is some evidence that in humans at least, the destructiveness of high phosphorus levels begins quite early in kidney disease. (read here)  In experimental dogs with induced, kidney failure, limiting phosphorus intake with a low-phosphorus diet increased their lifespan. (read here

Increased Water Intake And Combating Dehydration

Regardless of what pet food companies would like you to believe, the natural diet of cats and dogs is meat and entrails, not dry, baked kibble. Boned animal carcasses are about 70% water, whole rodents, about 66%, dry kibble pet foods about 8%.  Most dogs are better about drinking sufficient water to make up for that than cats. But in either species, even mild intermittent dehydration can be hard on the kidneys. Sure, feeding dry dog and cat foods is easiest on us. Less time, less hassle, less canned food odor, less halitosis, less cost. But when a pet faces kidney issues, one ought to consider abandoning dry kibble for a more natural, hydrating diet. At the least, one can also moisten dry pet foods. Begin with just a bit extra water – or, even better, chicken broth and feed multiple smaller meals throughout the day.

One of your pet’s body defense mechanism when faced with CKD, is to pass more water through what functional kidney tissue remains. I mentioned earlier, that is why pets with CKD tend to drink more. But that can also lead to dehydration if they don’t immediately replace that water by drinking. In experimental animals, periodic dehydration and sporadic water intake seem to make hypertension and kidney damage worse. (read here) There is also some early evidence that drinking more water slows the progress of CKD in humans as well. (read here)

You can do other things to encourage your pet to drink more: Have multiple water sources for your pet located throughout the house. All pets have their idiosyncrasies. Some drink more from wider shallow bowels than narrow deeper ones. Some prefer bottled water to tap. Some will drink more when their water is flavored – say an added ice cube of meat broth, tuna or clam juice. Some prefer a source of dripping water, others a fountain. Cats often prefer their water sources far from their litter boxes. When pets progress to the later stages of CKD (stage 3+) your veterinarian may suggest that that extra fluid be given at home by subcutaneous injection. That is not as extreme as it sounds. Because of their serious kidney issues, these pets are just as susceptible to over-hydration from fluids as dehydration. So the fluid must be given slowly and not over-zealously. That is also why it is much safer to give those fluids under the skin from where they are slowly absorbed rather than intravenously. Now giving fluid this way is not the same thing as peritoneal dialysis. That is a technique in which your veterinarian injects balanced fluids into the space surrounding your pets abdominal organs. After a period of time, your vet will attempt to remove as much of that fluid as possible – hoping that toxin have moved from the animal’s blood stream into the fluid.

Boarding CKD pets is unwise – hire an experienced pet sitter. Multiple trips to the vet’s office for subcutaneous fluid injections are also stressful for pets and owners alike. Most pet owners learn to master subcutaneous fluid administration with a little instruction. There are many videos on YouTube that will help show you how. I know we all have different talents; if you just can’t bring yourself to give fluids unaided, there is usually someone in a local animal rescue group who would he happy to give you the extra support you need.

Constipation is common in dehydrated debilitated cats that often need this therapy. Soupy foods rarely solves the problem without the aid of a mild cat laxative.  An alternative to that is more fiber in the pet’s diet.

Acid Base Balance

The bodies of pets with kidney disease are in danger of becoming too acidic . That situation is called metabolic acidosis . Normal cell metabolism – the everyday processes that all cells perform – creates hydrogen ions, the source of an acidic body environment. All animals rely on their kidneys to excrete those excess hydrogen ions and to create bicarbonate to keep their body’s acid:base in balance (their blood/body pH ) within tight limits. ( read here ) Cats and some dogs with kidney problems can have problems doing that. In-office blood gas analyzers (eg VetStat™, Element™ POC) can detect the acidity of your pet’s blood.  An increased anion gap is also a sign of too much body acidity. When an acid:base imbalance is detected, oral potassium citrate or sodium bicarbonate are the most commonly used alkalizing agent used to correct it in cats and dogs with CKD. 

Appetite Stimulants And Dealing With Poor Appetite

An almost universal occurrence in advanced CKD in cats and dogs is poor appetite. It probably occurs due to a number of things that advanced kidney disease generate: Increased circulating uremic toxins are a likely cause; so are the stomach and intestinal upsets that uremia often bring. Nausea may play a part too. The weakness and apathy of uremia-induced anemia can play a part as well. Whatever the causes, they are highly complex. In humans, it results in a loss of lean muscle mass (protein-energy wasting aka PEW) and it is the strongest predictor of approaching mortality. Weight loss is often accompanied by lower-than-normal blood albumin protein levels (although kidney protein leakage accounts for some of that drop, poor appetite does as well). Read why that occurs in humans here . It is very similar in our dogs and cats. Studies show that  faced with CKD, dogs with the lowest body scores pass away the soonest (read here) Thin cats are at increased risk of dying of multiple health issues including CKD too. ( read here )

There are a number of ways you might encourage your dog or cat to eat :
The aroma and texture of canned or freshly-made foods are preferred by most pets over the aroma and texture of dry kibble. Would you eat it? Broths, soups and gravies, poured over their main diet, often encourage pets to eat. So does verbal encouragement and some stroking from their owner. Warmed diets are often preferred over cold ones. Smaller multiple meals may result in daily food intake greater than just two or three. For cats, small amounts of high-aroma toppings (like sardines or clam juice) may do the trick.

There are also  a number of medications vets dispense hoping to improve a pet’s appetite. Mirtazapine (Remeron®) is sometimes helpful. It is also thought to reduce nausea. Doses in dogs and cats with kidney issues may need to be spaced farther apart. ( read here ) Mirtazapine is also sold as a transdermal (through the skin) ointment, Mirataz® When vomiting or nausea interplay with a lack of appetite, mirtazapine sometimes helps; but another common choice is maropitant (Cerenia®) The drug is best injected chilled. ( read here )  Cyproheptadine, an antihistamine, also seems to stimulate some cats to eat.  Whether dogs and cats with CKD benefit from antacids – other than ones given to bind phosphorus – is controversial. No one has confirmed that CKD causes high stomach acidity. 

The newest appetite stimulant on the market for pets is capromorelin. For dogs it is marketed as Entyce®. For cats it is marketed as  Elura® Read dog owner experience with this medication here. Cat owners’ experience here. Your feedback on its effects in your dog or cat with CKD or other health issues is appreciated.

Dogs and cats enjoy eating meat protein. All prescription diets marketed for pets with kidney issues are empirical (guess work) in their formulation and often less acceptable to a dog or a cat than what your pet was eating before. Their only confirmed benefit is that they all contain less phosphorus. All diets loose whatever beneficial effects they might have when your pet does not eat enough of it to maintain a healthy body weight. You can try several brands to see if your dog or cat prefers one over the other. You can also add a top coating of meat or fish broth that you prepare at home. Bullion is never a good substitute, flavor-enhancing ingredients high in phosphorus are often added. You can also prepare these lower protein lower phosphorus diets from scratch using human-grade ingredients from your supermarket. There are veterinary nutritional services that will assist you with custom recipes and the vitamin/mineral supplement that they all require. When you select meat ingredients for your dog or cat’s home-prepared diet, be sure that they have no added flavor enhancers. (read here)  

PUFAs – Polyunsaturated Omega 3 Fatty Acids

Omega 3 fatty acids, the oils mostly extracted from sea creatures, are thought by many to reduce inflammation throughout the body. ( read here )   Many commercial kidney diets marketed for pets add PUFAs, as well as antioxidants like vitamin E, C and beta carotene. One early study suggested that PUFAs were beneficial to dogs with experimental kidney failure. (read here)   Another contemplated their use in CKD in cats. ( read here ) Nothing of quality has been published regarding the usefulness of PUFAs in slowing the progression of CKD in humans. But a study by a group of veterinarians in the Netherlands did find that cats fed the commercial diet with the highest PUFA level appeared to live the longest. (read here)  The diets varied in many respects other than their PUFA content, but I am inclined to suggest a PUFA supplement for your pet  – if given in reasonable amounts for its body weight.  Just don’t get carried away. (read here)

Medications To Lower High Blood Pressure

Not all dogs and cats with kidney disease have high blood pressure. But many do and in those dogs and cats, the degree of elevation and the degree of protein leakage into their urine seem to go hand in hand – at least in dogs. (read here & here Most  veterinarians believe that high blood pressure damages a pet’s  kidneys. But it can be a vicious two-way street. Kidney disease can also be the cause of high blood pressure in dogs and cats (through the renin-angiotensin axis).  (read here & here) Giving medications that reduce blood pressure is a first-line treatment for CKD in humans as well. (read here & here)

The two groups of drugs that are in most common use for that in pets are angiotensin receptor blocking medications (ACE inhibitors, eg Fortekor®, Lotensin®, Enalapril® aka ACE-Is) and angiotensin receptor blockers ( ARBs such as telmisartan/  Semintra®). (read here)  The actions of both relax and widen the diameter of blood vessels (vasodilation) throughout the pet’s body enhancing blood flow (decreased vascular resistance). As blood flow meets less resistance, blood pressure goes down. That same effect is felt in your pet’s kidneys where pressure within the small blood filters (glomeruli) is reduced. These drugs may have other positive benefits. (read here) As of October 2018, Semintra® is FDA-approved for cats and available in the USA.  When ACE inhibitors are dispensed, your veterinarian needs to monitor your dog or cat’s blood potassium level closely because both drugs have been know to cause unsafe blood potassium levels and even cause blood creatine levels to increase rather than decrease. (read here)

Some veterinarians incorporate amlodipine (a calcium channel blocker) – a drug that reduces blood pressure in a different manner – when they feel that ACE-Is alone or with ARBs are not sufficient. Or when the decrease in the amount of protein leakage into the pet’s urine on ACE-Is/ARBs was not what they had hoped for. Amlodipine seems particularly effective in cats.

Giving a blood pressure-lowing medication to a pet with CKD is not without risk. When it produces a welcome drop in spilled urine protein that’s great. But initially, your vet will need to keep careful tabs on your pet’s blood creatinine level as well. It is not uncommon for these medications to bump up (cause a small rise) in blood creatinine levels. When it is small, that is probably tolerable and the pet may still live longer than it would have without the medication. But when it is a significant rise, the pet’s dose of blood pressure medication needs to be lowered and, in some cases, discontinued. It is unclear why this sometimes occurs. Perhaps it was only the abnormally high blood pressure in your pet’s remaining working glomeruli (the “super nephrons”) that was holding creatinine levels down. . Perhaps it was due to some other effect that compounds like ACE-Is have. We know these medications affect many systems. (read here) Some consider ARBs the safer option in advanced CKD – at least in humans. (read here) When blood pressure modifying drugs are used, your pet’s blood potassium levels need to be followed as well. Particularly at the start of a new medication or when symptoms advance. (read here)

When these unwanted and unexpected reactions occur, they are more likely to occur in the later stages of CKD than the earlier ones. They are also more likely to occur in pets that are dehydrated due to diarrhea, vomiting or the lack of water consumption. One also has to use these drugs cautiously in pets with advanced heart failure. Blood flow (and blood pressure within) their kidneys may already be too low due to their failing heart. The same goes for cat with evidence of hyperthyroidism. In cats, hyperthyroidism sometimes masks serious kidney issues.

Creatinine is only a marker for the many uremic toxins that are thought to rise in tandem with it. In pets that don’t tolerate ACE inhibitors or ARBs well, focusing on a low-phosphorus diet might be a safer option. 

When Should My Veterinarian Start Giving My Pet Medications To Lower Its Blood Pressure?

Ideally, it would begin when your veterinarian confirmed that your pet’s resting blood pressure had begun to rise above normal. But there are problems here. I mentioned earlier how difficult it is to get accurate blood pressure readings when pets visit animal hospitals. So many vets make the decision based on elevated levels of albumin protein in your pet ‘s urine. The two are assumed to go hand in hand. There really isn’t any evidence that beginning these medications before there is substantial urine protein leakage is of any benefit. 

A small study of dogs that Elanco conducted last year muddied the waters still further. They found that a commonly used ACE-I (benazepril) did lower urine protein in dogs. But it did not increase the lifespans of the 24 dogs to which it was given. It also confirmed that benazepril bumps up blood creatinine levels. You can read that study here. As the authors point out, 49 dogs are a small number – perhaps too small to note modest benefits of ACE treatment.

How can this be? Conflicting and perplexing results are seen across the entire spectrum of CKD field studies in dogs and cats. I think it is quite likely that there are a number of subsets of CKD in our dogs and cats as well as pets with multiple, unidentified, coexisting health (or genetic) issues. I believe that is why the results of these studies are so perplexing. Taking the effects of one treatment plan in a dog or cat with naturally occurring kidney failure and comparing it to the effect of the same treatment plan in another kidney failure patient is not valid. Just because we find protein leakage and kidney dysfunction doesn’t mean that the underlying causes and progression are the same in both pets. Until we understand this better, its going to be hit or miss with the drugs, nutrition and lifestyle changes we veterinarians suggest. Some pets will benefit from one treatment; other from another. Most startling and gratifying to me is that the study was paid for by Elanco, the makers of Fortekor®, the benazepril formula for dogs and cats. There are oodles of glowing reports on the benefit of this or that for pets with CKD. Elanco’s is the only one I know of where the folks picking up the tab (paying the bill) did not get the news they were hoping for. They obviously placed your pet’s health above their bottom line. Similar challenges using ACE-Is and ARBs confront physicians treating CKD when their patients have multiple health issues.

Veterinarians are also uncertain as to which dose at which stage of the disease is appropriate. One never wants blood flow through the kidneys to drop so low that the organ is starved of oxygen or remaining nephrons are injured. I would be particularly cautious in pets receiving NSAIDs (eg Rimadyl®, Previcox®) for arthritis or diuretics (eg Lasix®, spironolactone) for heart issues or that are at risk of dehydration or all three (the “triple whammy”). ( read here )   

Dealing With Anemia When It Finally Arrives

As CKD progresses, it is common for cats and dogs to become anemic. By the time the pet’s packed cell volume (PCV) drops into the 20s, its energy level, heart and breathing rate will be affected. (stage 3-4). I mentioned earlier that the main cause of this anemia is insufficient kidney production of erythropoietin. At that stage, some veterinarians give their clients the option of opting for erythropoietin or darbepoetin (Aranesp®) subcutaneous injections – both of which stimulate the formation of red blood cells. Darbepoetin injections have the longer period of action – sometimes as long as two weeks. Both medications can take 3-4 weeks to show improvement in the pet’s PVC or RBC numbers. A rather high number of pets have reactions to multiple injections of either product – but less with darbepoetin than erythropoietin. In an extensive 2017 study, there was no significant differences in the life span of dogs that responded to darbepoetin treatment and those that did not. (read here ) Many vets will check these pets for iron deficiency. When present, oral or injectable iron supplementation is desirable.

A blood transfusion is also possible. It is rarely suggested or performed. First, it is expensive. Second, it is quite stressful – the health of an advanced CKD pet is already fragile. Third, there is the possibility of an immune reaction against the transfused blood. Lastly, transfused red blood cells do not tend to last very long in uremic patients.

Are There New Medications In Development That Might Help?

A lot of pioneering work comes out of the Broad Institute (rhymes with road). They are interested in how the genetics of dogs and cats relate to the diseases that affect them because they believe that a better understanding of the causes of pet diseases leads to a better understanding of the causes of human diseases. One of the interesting compounds they are studying is a TRPC5-inhibitor that seems to have abilities to retard the progress of several forms of CKD. (read here) These are early studies in rats. Perhaps something useful will come out of them, perhaps not. ( I spoke to one of the authors about the high incidence of CKD in elderly cats and dogs. She was unaware of that, but glad to know it ). Another experimental drug combination is LCZ696 (sacubitril/valsartan aka Entresto®) which, some hope, might slow the progress of CKD.  (read hereThere are other compounds under study for a particular form of human kidney disease.  They are not the forms of kidney disease commonly seen in dogs and cats, but perhaps there will be cases where they would be helpful:  Sparsentan (RE-021) is one of them. It combines some of the actions of ARBs with those that reduce the effects of endothelins, compounds that increase blood pressure. If this drug has any potential uses in veterinary medicine remains unknown. (read here )  Sulodexide is a compound that might be helpful in reducing protein leakage into the urine (microalbuminuria) in humans whose CKD relates to diabetes. One study found it effective another study did  not.  If it has been used in dogs or cats, I am unaware of it.

What About Stem Cell Treatments?

Colorado State University had a pilot program using feline fat (aka adipose-derived MSCs) as a source of stem cells (mesenchymal stem cells =  adipose-derived MSCs) in hopes that introducing them into cats with renal (kidney) disease would halt or slow the disease. Their first attempts were in 2009 and clinical trials continued through 2015. The sequence of the tests are a bit confusing to me. But In one report, two out of the four cats were said to have experienced “modest improvement” after intrarenal (placed directly into the kidney) injection. I believe that in their 2013 study, the stem cells were given intravenously (a lot easier procedure). In those pilot studies, the 16 cats enrolled were said to “not have experienced a clinically relevant improvement ” a polite way of saying that the treatment was ineffective.  I believe that the veterinarian who conducted those studies has moved on to the vet school at Ohio State University. I also believe that in 2011, a group of veterinarians at the AMC in New York began injecting fat-derived stem cells into the kidneys of cats with late stage CKD. No results of those tests that I know of have been announced.

There is a lot of interest in regenerative medicine across the span of human and animal disease. No one has regenerated kidneys with this technique, but some early data suggests that perhaps, in some circumstances, the progress of CKD might be slowed. (read here) The field is in its infancy.

There is considerable hype and quackery across the entire stem cell field. The internet is full of glowing testimonials. ( see here ) I inquired of one of the pioneering physicians in mesenchymal stem cell research, the Chairman of the Stem Cell Biology and Regenerative Medicine program at the University of Southern California. This was his reply: “What they are doing is isolating what are referred to as mesenchymal stem cell. There is no evidence these directly rebuild kidney tissue, or that they stimulate intrinsic regeneration. There have been studies that show they have an anti-inflammatory role so they may depress inflammatory responses that are contributing to the progression of kidney disease. However, I would be skeptical of any role without some very robust pre and post treatment quantities metric.

Another stem cell research scientist at Kansas State University had similar thoughts: “These products are marketed without the usual regulatory process if they are “minimally manipulated”. This is in response to the public’s desire to have access to new therapies. But I understand that the FDA is cracking down on these for humans. [The Company] has capitalized on a regulatory ‘loop hole’. Unfortunately this situation may reduce the pressure for controlled clinical studies.”

If you elect to try them on your cat or dog, I would appreciate you letting me know what, if any, measurable metrics (symptoms) improved when other changes were not made in your pet’s treatment plan. Improvements like body weight, anemia, BUN, Creatinine, proteinuria or your pet’s blood phosphorus level.  

Do Cats Have Some Unique Kidney-Related Risks That Us and Dogs Do Not Generally Have?

Yes.

There is a relatively high incidence of hyperthyroidism in older cats. Veterinarians are uncertain why. Hyperthyroidism often leads to high blood pressure – a known risk for kidney disease. In fact, it is very common for feline hyperthyroidism and CKD to exist in the same cat. Hyperthyroidism also leads to excessive drinking. That increased water, flushed through the kidneys, masks the CKD until the hyperthyroidism is corrected with drugs or radiation. At that point, some cats go into kidney (renal ) failure. So at the least, elevated urine microalbuminuria/UPCR ratios or creatinine/SDMA levels in your elderly cat might  suggest to your vet that a thyroid function test (T4) needs to be run as well.  Kidney function tests are generally run before non-reversable treatments for hyperthyroidism like radioiodine are attempted. Several articles have appeared that suggest a link between a common disease of cats, bartonellosis, transmitted by fleas, and kidney disease. (read here ,here , here and here) These were all human cases and none suggested that bartonella as a cause of CKD in cats. Perhaps that ought to be examined. Fleas can also transmit bartonella to dogs. (read here) See Idexx bartonella PCR tests options here

How About Kidney Risks That Are More Common In Dogs?

Elderly dogs are particularly disposed to heart valve issues (generally the mitral valve first).  (read here) Once a pet’s heart no longer pumps sufficient blood through its kidneys, other negative process are probably also in play. (read here& here) Some veterinarians believe that the reverse may also be the case – dogs with kidney disease may be more likely to develop heart issues. ( read here )  So a proBNP  heart test might be a good choice when kidney tests are abnormal – particularly if your veterinarian detects abnormal heart sounds and/or other evidence of poor circulation.

Arthritis and kidney problems tend to show up at about the same time in a dog’s life.  Although nothing is proven, one might decide to use NSAIDs cautiously in dogs that show signs of arthritis and concurrent signs of CKD. It’s a quality of life issue that owners have to decide for themselves – is mobility and freedom from pain more important than perhaps a bit longer life. There might soon be medications for dogs with arthritis that do not have potential kidney consequences. ( read here )   No long-term NSAIDs are approved for use in cats. ( read here )

What About Hemodialysis Or A Kidney Transplant?

Long-term hemodialysis is not readily available for dogs or cats. I am not sure why that is, since it is technically possible. When it is performed, it is usually in a university setting and being done for one of several causes of sudden kidney injury. Things like antifreeze, grape/raisin poisoning, nibbling on Easter lilies etc. – causes that might resolve in time when dialysis give a pet that time. It is also occasionally used short-term when the urine outlet tube(s) from the kidney (ureters) become plugged (blocked) with stones or some other obstruction. Standard pet dialysis treatments take 4-6 hours, 2-3 times a week. Long term, it is expensive and a strain on both pet and owner.

There are also veterinary teaching hospitals that perform feline kidney transplants. Transplants are rarely performed on dogs because the current success rate is lower. The University of Pennsylvania School of Veterinary Medicine has the most historical experience performing them. (read here & here ) The surgical technique, pre and post surgical care  vary by institution. PennVet claimed a 60-70% one-year post-transplant feline survival rate (As opposed to a 97% success rate in humans given human-donor kidneys (cats being smaller are more difficult).  I believe that the most common complication, when one occurs, is scarring and inflammation that obstructs the passage of urine from the transplanted kidney (retroperitoneal fibrosis) (read here)  Cats with concurrent health issues or advanced age are poor candidates. I do not know of any programs that currently accept dogs but could be unaware of ones that do. Dogs tend to reject transplanted kidney quite rapidly. They also suffer more infections, blood clots, etc. after the surgery than cats. Kidney transplants are not a cure – the animals must take anti-rejection medications for the rest of their lives (at a current cost of about $1,000 per year + periodic testing). The bill for the surgery for one cat at PennVet in 2015 was $16,000, plus airfare, hotels, medical tests and follow-up appointments. With the owners hoping the final bill would not exceed $30,000. Vets in the UK view the ethics of this procedure differently and could not agree. Some found donor cats acceptable, others felt that only kidneys from cats that had died of other causes should be used. (read here) Cost figures, US, UK and European decisions may be different at the time you read this article. To the best of my knowledge the last current information on pubmed dates to 2016.

The International Veterinary Renal Interest Society, IRIS, recommends considering “heroic” procedures for pets in stage 4  kidney failure: implanted feeding tubes, stomach ports, multiple IVs, peritoneal dialysis and hospice care. I cannot imagine a dog or a cat wanting to be put through that cruel agony. Your pet loved you for many years. The least you can do for your friend at this point in its life is to help send it peacefully to Heaven. In my opinion, is the only merciful thing to do. 

How Much Longer Will My Cat Live?

The Animal Medical Center (AMC) is the premier animal hospital in New York City. In 2008, they reviewed the data and outcomes of 211 cats that had evidence of chronic kidney disease (blood creatine levels at or above 2.3 mg/dL or 203µmol/L). The International Renal Interest Society divides progressive kidney failure in cats into stages. They are more cautious than many diagnostic laboratories and consider a fasting blood creatinine level above 1.4 mg/dL (125 µmol/L) for a dog or 1.6 mg/dL (140 µmol/L) for a cat to be an indication of kidney disease. By the time a cat reaches a fasting blood creatinine level of 2.3 mg/dL, as in the AMC study, it would be in IRIS stage II (1.6–2.8 mg/dL or 140–250 µmol/L). In the AMC study, the median survival time for cats in that stage was 3.15 years. For cats that came to them in IRIS stage III, (2.9-5.0 mg/dL or 251–440 µmol/L) the median survival time was 2.13 years. When the cat’s fasting blood creatinine exceeded 4 mg/dL or 354 µmol/L, their median survival time was 4.1 months. When cats arrived in IRIS stage IV (greater than 5.0 mg/dL or 442 µmol/L) their median survival time was about 3.5 months. The median survival time from the point cats became seriously anemic was 3.3 months. The median survival time once the cat had begun to loose weight was just a bit over one year. The median survival time from the point that subcutaneous fluids were begun was 9 months. Unfortunately, the study did not examine whether the treatments veterinarians suggest for CKD extended the cat’s lives. You can read the article’s abstract here. If you would like to read the full article ask me for Boyd2008.pdf  Similar data does not exist for dogs.

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