What pet owners should know about kidney function and the diagnosis and management of chronic kidney disease in dogs and cats

The kidney is an organ made up of hundreds of thousands of functional units called nephrons (see diagram of a nephron on the left). Each nephron is composed of a little filter called the glomerulus (plural, glomeruli) and a long passageway called the tubule. All of the tubules eventually converge to form a collecting system that brings the waste products as urine to the bladder. As the heart beats, pressure within the small blood vessels of the kidney causes blood to be filtered through the glomeruli -- a filtrate consisting of water and small substances (such as sugars, amino acids, electrolytes, small proteins, and waste products) is forced into the tubules while blood cells and larger proteins remain in the blood. Then, as the fluid flows down the tubules, the kidneys reclaim the water and substances the body needs and allow the waste products and any excess water to go out into the urine. In terms of volume, more than 99% of the fluid that is filtered is returned to the blood and less than 1% is excreted. The famous renal physiologist, Homer W. Smith once said, "Superficially it might be said that the function of the kidneys is to make urine; but in a more considered view, one can say that the kidneys make the stuff of philosophy itself." This was an eloquent way of saying that the kidneys are more concerned with what they retain in the body than what goes out in the urine. The real job of the kidneys is to regulate and keep stable the volume and composition of the body's internal fluids. The urine the kidneys produce is merely a by-product of that process of conservation. The kidneys also have some other important functions such as producing a hormone (called erythropoietin) that stimulates red blood cell production by the bone marrow and modifying vitamin D derived from the diet into its final active form (called calcitriol).

The most common form of kidney disease in dogs and cats comes on very slowly over time and consequently is known as chronic kidney disease (or CKD). By the time the disease is advanced, the kidneys can be so altered by scarring and inflammation that it can be nearly impossible to determine what exactly initiated the disease process. In his classic textbook, "Clinical Nephrology," Solomon Papper offered the following quotation from the American pathologist, Simeon Burt Wolbach to make this point: "It is often difficult to ascertain the nature of the edifice that has burnt down from a study of the ashes." Unfortunately, because dogs and cats cannot tell us how they feel, kidney disease often is very advanced by the time it is recognized by pet owners and veterinarians.

For the discerning pet owner, the first clue about the possible presence of chronic kidney disease is that his or her pet is producing a larger volume of urine than previously and is drinking more water. These changes occur because, as kidney disease progresses and nephrons are lost, the remaining functional nephrons must handle a much increased load of water and small substances being filtered from the blood, which leads to production of a larger than normal volume of dilute urine. The animal drinks more to compensate for the loss of an excessive amount of water in the urine. It is easier for a dog owner to recognize these changes, called "polyuria" (increased urine production) and "polydipsia" (increased water consumption) than it is for a cat owner. This is because dogs typically are taken outside to urinate and, if they are producing more urine and not allowed out frequently enough, they will urinate in the house, which will get the attention of their owners. The owner also may notice that the dog's water bowl needs to be refilled more frequently throughout the day. It's a little more challenging with cats because they normally don't drink all of the water in the big bowls they typically are provided and they usually urinate in a litter box. It takes a very observant owner to recognize increased water consumption in a cat, but it's a little easier to notice when the litter box is filling up with an increasing number of wet clumps of litter and needs to be cleaned out more frequently. These changes (polyuria and polydipsia) are the first things to be noticed but, when they occur, the kidneys have already lost about two-thirds of their function and the disease actually is fairly advanced.

The next thing that occurs in dogs and cats with chronic kidney disease is something that often is noticed by the veterinarian when performing blood tests on older pets as part of routine geriatric care. When the disease progresses to an advanced stage, the overall filtration function of the kidneys decreases to the point that waste products begin to build up in the blood. Two tests for waste products ("blood urea nitrogen" or "BUN" and "creatinine") are included on blood chemistry profiles commonly performed by veterinarians. Unfortunately, when the concentrations of these particular waste products begin to increase in the blood outside of the normal reference range for the laboratory, the kidneys already have lost about 75% of their function. If the veterinarian performs blood tests on a recurring basis as the animal ages, it may be possible to detect deterioration in kidney function by consistent increases in BUN and creatinine even if they are still within the laboratory's normal reference range. Thus, yearly visits to the veterinarian as the animal gets older may allow earlier detection of chronic kidney disease. Later, when the kidneys lose 85% of their function, the concentration of the mineral phosphorus goes up in the blood.

Recently, a new blood test called "symmetric dimethylarginine" or "SDMA" has been introduced that may allow veterinarians to recognize kidney disease much earlier -- when the kidneys have lost about 40% of their function. Potentially, the SDMA test could allow veterinarians to identify kidney disease in dogs and cats even before the changes in water intake and urine production are recognized. However, veterinary researchers and clinicians need more experience using the SDMA test to determine its full value in identifying early kidney disease in dogs and cats.

The International Renal Interest Society (IRIS) has developed guidelines (http://www.iris-kidney.com/guidelines/staging.html) to help veterinarians recognize and classify chronic kidney disease in dogs and cats. These guidelines divide the progression of chronic kidney disease into four different stages based on clinical findings and laboratory test results, which help veterinarians recognize kidney disease and treat it appropriately as early as possible.

Once kidney disease is advanced and waste products such as BUN and creatinine increase in the blood, other more obvious signs of illness such as lethargy, loss of appetite, weight loss, and poor condition of the hair coat may become apparent to pet owners, but unfortunately the disease is quite advanced at this point. Dogs with advanced kidney disease often also experience vomiting episodes, but this is less common in affected cats. When the disease reaches a point at which the animal is losing a lot of fluid in the urine, not eating and drinking, and possibly vomiting frequently, severe dehydration as well as chemical imbalances (abnormal concentrations of minerals in blood, excessive acidity of body fluids) can occur that worsen the animal's condition and be life-threatening if not treated properly. The goal is for the owner to recognize early signs of chronic kidney disease (increased water intake and urine production) and seek veterinary care promptly. If chronic progressive kidney disease can be recognized at an earlier stage, it is more likely the disease can be managed and its progression potentially slowed by appropriate medical treatment.

When evaluating a pet with possible chronic kidney disease, the veterinarian will try to determine the size of the animal's kidneys, because the kidneys become smaller and more firm (from scarring) with progressive disease. In many cats, it is quite easy for the veterinarian to estimate the size and texture of the kidneys because the kidneys often can be readily felt (palpated) on examination of the animal's abdomen. It is more difficult to palpate the kidneys in dogs however. In both species, the veterinarian can obtain more information about the size of the kidneys by taking a radiograph of the animal's abdomen. Abdominal ultrasound examination will allow the veterinarian to evaluate not only the size and shape of the kidneys but also their internal structure. These imaging tools allow the veterinarian to acquire additional information about the condition of the pet's kidneys.

If the animal is well hydrated and has relatively normal electrolyte and acid base balance as determined by blood chemistry tests, the veterinarian can focus on medical management that involves primarily dietary modifications.

It is crucial that dogs and cats with chronic kidney disease have fresh water available to them at all times. They cannot concentrate their urine adequately and lose an excessive amount of water in the large volume of urine they produce. Consequently, they must drink large quantities of water to maintain their hydration. An owner should never withhold water from a dog or cat with chronic kidney disease thinking it will make them urinate less. On the contrary, restricting their water intake will only put them in danger of becoming dehydrated and more seriously ill.

One of the most important dietary modifications that can be made for a dog or cat with chronic kidney disease is restriction of phosphorus intake, which can reverse an important detrimental compensatory mechanism that occurs in chronic kidney disease, called renal secondary hyperparathyroidism. Dietary phosphorus restriction also potentially can limit some of the progressive structural damage that occurs in the kidneys as a consequence of calcium and phosphorus imbalance. Provision of a diet that is limited to a moderate amount of high quality protein also may be beneficial, but the ideal amount of protein to feed a dog or cat with chronic kidney disease has been debated for many years. It is important to provide sufficient protein to maintain as ideal a body weight and hair coat condition as possible, but not an excessive amount of protein. In addition to body weight, the veterinarian can use tools such as body condition score and the concentration of a protein called albumin in the blood to help assess the animal's nutritional status.

Fortunately, several commercial therapeutic pet foods designed specifically for dogs and cats with chronic kidney disease are available. Usually, it is possible to find a product or combination of products that the pet will accept. Effective diets typically are restricted in phosphorus, protein and sodium and supplemented with polyunsaturated fat as well as potassium (in renal diets for cats). In some cases, the owner must resort to a making a homemade diet, but this approach is less than ideal because it is difficult to ensure that such diets are balanced and contain all of the necessary vitamins and minerals in addition to the right balance of protein, carbohydrate, and fat. Changes in the diet work best if they can be instituted when the pet is in IRIS Stage 2 to 3 of chronic kidney disease and still has a reasonably good appetite. Changes in the animal's diet should be made over several weeks, gradually increasing the amount of the new diet fed while decreasing the amount of the old diet until the pet has been completely transitioned to the new diet. In one study of cats with chronic kidney disease, those eating a commercial kidney diet survived up to twice as long as those eating a regular diet.

Additional potassium supplementation also may be needed in some cats with chronic kidney disease. If using a potassium source such as potassium gluconate, the gluconate when metabolized will aid in alkalinizing the body fluids, which can be beneficial in pets with advanced kidney disease that have excessive acidity of their body fluids. It also is important to be aware of the sodium content of the diet. The rationale behind sodium restriction is that blood pressure will be better controlled and the risk of increased blood pressure (hypertension) decreased. The effect of sodium restriction on blood pressure however may be limited, and too much sodium restriction may increase the activity of a hormonal regulatory system in the body that promotes sodium retention and increases potassium excretion (i.e. the renin-angiotensin-aldosterone system). Increased activity of this system can lead to further loss of potassium in the urine and contribute to depletion of potassium in the body.

If dietary restriction of phosphorus alone is not sufficient to reverse renal secondary hyperparathyroidism, the veterinarian may suggest adding phosphorus binders, which are drugs that bind phosphorus in the intestinal tract, prevent it being absorbed from the food, and allow it to be excreted in the feces. These medications should be given to the pet around the time of feeding to maximize their benefit. Some of these phosphorus binders are available over the counter (such as calcium carbonate) and others are prescription products. They should, however, be used under the supervision of a veterinarian because adverse effects may occur if too much phosphorus binder is given.

In pets (especially dogs) with chronic kidney disease that are vomiting frequently, the veterinarian may recommend acid suppressive medications such famotidine. Cats with chronic kidney disease vomit less frequently than do affected dogs, and they are less likely to develop stomach ulcers as compared to dogs. Thus, the usefulness of acid suppressive medications in cats with chronic kidney disease recently has been called into question. Sometimes, drugs to stimulate appetite (mirtazapine) are used in cats with chronic kidney disease, and mirtazapine also decreases the frequency of vomiting. Anti-emetic drugs (such as maropitant or ondansetron) can be used if vomiting is a persistent problem in dogs with chronic kidney disease.

Angiotensin II is a hormone that is part of the renin-angiotensin-aldosterone system mentioned above. It helps maintain blood pressure by causing constriction of blood vessels and promoting sodium retention by the kidneys. However, it can have some detrimental effects in dogs and cats with chronic kidney disease such as worsening protein loss in the urine and promoting scarring and inflammation in the kidneys. Drugs that decrease production of angiotensin II (angiotensin converting enzyme or ACE inhibitors such as benazepril) or block its ability bind with its receptor (angiotensin II receptor blockers such as telmisartan) are used in the hope they can limit some of the detrimental effects of angiotensin II that may occur in dogs and cats with chronic kidney disease and possibly limit the progression of the disease. These drugs may have only a modest effect on systemic blood pressure, and some dogs and cats with chronic kidney disease and high blood pressure may require additional medications, usually a drug that blocks the effect of calcium on the constriction of blood vessels (amlodipine). It sometimes can be difficult to tell if a cat or dog really has high blood pressure that needs to be treated because dogs and cats (like many people) are subject to what is called "white coat artifact." This term refers to the observation that some people's blood pressure goes up when they go to the doctor's office and are worried about their blood pressure. Dogs and cats obviously don't worry about their blood pressure, but they usually are very nervous when taken for a visit to the veterinarian. Thus, a similar effect can occur. It requires a patient, well-trained technician measuring the pet's blood pressure carefully and repeatedly (often in the calming presence of the pet's owner) to try and determine if the animal actually has high blood pressure that requires treatment. Nevertheless, it is important to establish whether or not a dog or cat with chronic kidney disease does indeed have high blood pressure because hypertension is a treatable complication that, if adequately controlled, may improve the well-being of the pet and possibly slow the progression of the kidney disease.

Some pets with advanced kidney disease develop problems that arise from the kidney's role in regulating red blood cell production and calcium balance. In such patients, additional drugs such as erythropoietin and calcitriol may be used. Use of these medications requires sophisticated understanding of the abnormalities that can occur in advanced kidney disease and they are best used by specialists in veterinary internal medicine in conjunction with owners who understand the potential complications of such treatment.

In some instances, owners can be taught to administer electrolyte-containing fluids such as lactated Ringer's solution subcutaneously (i.e., under the skin) to their cats or small dogs with chronic kidney disease when the animal is not eating and drinking enough to maintain its hydration. Doing so successfully however requires an owner who is not squeamish about needles and a pet that will tolerate the treatment at home with minimal restraint. Sometimes, in cats with advanced chronic kidney disease, a long-term feeding tube can be placed in the stomach (i.e., gastrostomy tube) that will allow the owner to easily administer liquefied food, water, and medications. The gastrostomy tube can be tolerated amazingly well by many cats with chronic kidney disease.

Owners sometimes ask how long their pet will live with chronic kidney disease. The length of time a dog or cat with chronic kidney disease will live is impossible to predict with certainty because the rate of progression of chronic kidney disease varies considerably among individual animals. The veterinarian can get some idea of the rate of progression of an individual animal's chronic kidney disease by following the concentration of creatinine in the blood over many months with the trend of changes in serum creatinine concentration over time being used to estimate how rapidly the kidney disease is progressing. Following progression in this way also can help the veterinarian determine if changes in medical management are helping slow the rate of progression of the disease. Some dogs and cats with chronic kidney disease can live several years with conscientious management of their disease by the veterinarian and pet owner.

July 10, 2019