Most people know that the primary job of the kidneys is to clear waste products from the blood, but it also is important to know a little bit about how this is done, what else the kidneys do, and what happens when things go wrong.

The kidney is an organ made up of hundreds of thousands of functional units called nephrons (see diagram of a nephron on the left).  Dogs and cats and people are born with as many nephrons as they will ever have and unfortunately, new nephrons cannot be produced.  The good news is dogs, cats, and people have more than twice the number of nephrons needed for adequate kidney function and that’s why people with healthy kidneys can donate a kidney and still live normally.  Each nephron is composed of a little filter called the glomerulus (plural = glomeruli) and a long passageway beyond the glomerulus called the tubule.  All the tubules from each nephron 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 glomeruli causes blood to be filtered.  The 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.  Think of the glomerulus as a spaghetti strainer.  When water, salt and spaghetti is poured into the strainer, water (the liquid portion of blood known as plasma) and salt (electrolytes within the plasma) freely pass through the strainer, but the spaghetti (blood cells and proteins in the plasma) are retained.  Then, as the filtered fluid flows down the tubules, the kidneys return water and substances the body needs back to the blood stream 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 kidney 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 after the blood has been filtered through the glomeruli.  For example, when you exercise and perspire, your kidneys will conserve body water by producing a small amount of concentrated (dark yellow) urine.  If you were to drink lemonade to excess and overhydrate, your kidneys would excrete the excessive body water by producing a large volume of dilute (almost clear) urine.  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) involved in both calcium and phosphate balance in the body.

The most common form of kidney disease in dogs and cats comes on very slowly over time is known as chronic kidney disease (CKD) and is caused by loss of nephrons.  If any portion of the nephron is irreversibly damaged, the nephron ceases to function and is replaced by fibrous scar tissue.  CKD is often progressive and 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 building 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 (greater than three quarters of the nephrons have been lost) by the time it is recognized by pet owners and veterinarians.

For the discerning caregiver, the first clue about the possible presence of CKD 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 proportionally increased load of water and small substances being filtered from the blood, which leads to production of a larger than normal volume of dilute, usually watery appearing urine.  The kidneys cannot produce concentrated urine in response to dehydration and the pet’s urine is always dilute and voluminous.  Thirst is stimulated in an attempt to “keep up” with the increased volume of urine and water loss from the body.  The animal drinks more to compensate for the loss of an excessive amount of water in the urine.  It is often easier for a dog owner to recognize these changes, called "polyuria" (increased urine production) and "polydipsia" (increased thirst and 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, 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 the water in the big bowls they typically are provided and they usually urinate in a litter box.  An observant owner may 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 often the first things to be noticed but, when they occur, the kidneys have already lost about two-thirds of their function, and the disease is fairly advanced.

The next thing that occurs in dogs and cats with CKD is something that often is noticed by the veterinarian when performing blood tests on older pets as part of routine geriatric care.  When the kidney 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.  Three tests for waste products (blood urea nitrogen or BUN, creatinine, and SDMA) are included on blood chemistry profiles commonly performed by veterinarians.  Of these three, BUN is the least sensitive and least specific since it can be affected by diet, bleeding into the stomach and small intestine, and liver function and therefore should not be relied upon as an accurate marker of kidney function.  Creatinine is more specific for kidney function, but it is not very sensitive, increasing outside of the laboratory reference range only when the majority of the nephrons of both kidneys cease to 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 creatinine even if it is still within the laboratory's normal reference range.  Thus, yearly visits to the veterinarian as the animal gets older may allow earlier detection of CKD.  A newer blood test called symmetric dimethylarginine or SDMA has been introduced that may allow veterinarians to recognize kidney disease much earlier in dogs and cats; even before the changes in water intake and urine production are recognized.  Just like following trends in creatinine as pets age, the trend of increasing SDMA while it is still within the laboratory reference range can help your veterinarian diagnose CKD in its early stages.  In dogs and cats, decreased urine concentration may occur before an increase in creatinine or SDMA and thus obtaining a urine sample and following trends in urine concentration is also important.  It’s best to evaluate both creatinine and SDMA as both provide important information and, in some cases, creatinine may increase prior to increases in SDMA.  Later, when the kidneys lose about 85% of their function, the concentration of the mineral phosphorus goes up in the blood and can be detected on a blood chemistry panel. 

Additional findings of CKD your veterinarian may observe are high blood pressure (hypertension) and excessive protein in the urine (proteinuria).  Hypertension is a common complication in dogs and cats with CKD, and it can cause additional damage to the kidneys as well as the heart (e.g., a new heart murmur), eyes (e.g., sudden blindness), and brain (e.g., seizures or wobbly gait).  Hypertensive damage to the eyes may be observed in the back of the eye (the retina) using an ophthalmoscope.  Proteinuria in CKD patients may be caused by high blood pressure in the glomeruli or damage to the glomeruli that allows blood proteins to pass through the glomerular filters which, when normal ensure that proteins of high molecular weight remain in the blood.  Think of a damaged spaghetti strainer that allows spaghetti passing through the strainer along with the water and salt.  Proteinuria may also result from damage to the tubular portion of the nephron.  Proteinuria is not just an important diagnostic finding in dogs and cats with CKD; like high blood pressure it can damage the kidneys and hasten a decrease in kidney function.

The International Renal Interest Society (IRIS) has developed guidelines to help veterinarians recognize and classify CKD in dogs and cats.  These guidelines divide the progression of CKD into four different stages based on clinical findings and laboratory test results, which help veterinarians recognize kidney disease and tailor treatments based on the stage of disease.

Once kidney disease is advanced and waste products 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, but unfortunately the disease is quite advanced at this point.  Dogs with advanced kidney disease often also experience vomiting episodes.  Cats typically experience less vomiting but may still be nauseous as manifest by progressive weight loss.  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 promptly and properly.  

Due to the irreversible nature of the disease, the goal is for the owner to perform routine health care evaluations as their animals age and to recognize early signs of CKD (increased water intake and urine production, gradual weight loss and loss of muscle mass) and seek veterinary care promptly.  If CKD can be recognized at an earlier stage, it is more likely the disease can be managed and its progression slowed by appropriate medical treatment.

When evaluating a pet with possible CKD, the veterinarian will try to determine the size of the animal's kidneys, because the kidneys become smaller and firmer (from scarring) with progressive disease.  In many cats, it may be 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.  In addition, 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 also allow the veterinarian to diagnose potentially treatable complications like stones and infection within the kidneys.

If the animal is well hydrated, not hypertensive or losing proteins in the urine 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 CKD always have fresh water available to them.  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 stay properly hydrated.  An owner should never withhold water from a dog or cat with CKD 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 CKD is restriction of phosphorus intake, which can reverse an important detrimental compensatory mechanism that can cause mineral and bone disorders.  Dietary phosphorus restriction can also potentially limit some of the progressive structural damage that occurs in the kidneys because 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 CKD 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 to help assess the animal's nutritional status.

Fortunately, several commercial therapeutic pet foods designed specifically for dogs and cats with CKD 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 but not dogs).  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 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 or early Stage 3 of CKD 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 several studies of dogs and cats with CKD, those eating a commercial kidney diet survived up to two to three times longer than those eating a regular diet.

Additional potassium supplementation (e.g., potassium gluconate or potassium citrate) also may be needed in some cats with CKD.  If using a potassium gluconate, the gluconate when metabolized will aid in combating the acid build up in body fluids, and be beneficial in pets with advanced kidney disease.  It also is important to be aware of the sodium content of the diet.  The rationale behind dietary sodium reduction is that blood pressure will be better controlled and the risk of increased blood pressure 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 (i.e. the renin-angiotensin-aldosterone system) in the body that promotes sodium retention and increases potassium excretion.  Increased activity of this system can lead to further loss of potassium in the urine and contribute to depletion of potassium in the body as well as high blood pressure.

If dietary restriction of phosphorus alone is not sufficient to reverse the mineral and bone disorder, 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 stool.  These medications should be ideally mixed with the food or, if that is not acceptable to the pet, given in pill form at the time of feeding to maximize their benefit.  Some of these phosphorus binders are available over the counter (e.g., 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.  A new blood test (FGF-23) is available to help manage the phosphorus retention that occurs as nephrons are lost in cats with CKD.  Monitoring FGF-23 concentrations guides the veterinarian as to when further dietary phosphorus restriction and increased doses of phosphorus binders are needed.

Patients with advanced CKD commonly have a poor appetite and associated weight loss, most likely due to a build-up of substances in the blood that supress appetite.  Paying close attention to caloric intake is important to in order to identify and address decreased appetite and weight loss early on.  Medications (e.g., mirtazapine and capromorelin) can be prescribed to combat poor appetite and weight loss and help maintain caloric intake.  Additionally, nausea and vomiting may be observed and treated with anti-emetic and/or anti-nausea medications (e.g., ondansetron and maropitant).  In late-stage CKD, if appetite fails to respond to these therapies, stomach acid suppressive medication may also be employed (e.g., omeprazole).  Proactively addressing these concerns facilitates feeding an ideal diet for the CKD patient.

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 CKD such as worsening proteinuria, hypertension, 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 action (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 CKD and possibly slow the progression of the disease.  These drugs can have further benefit by decreasing proteinuria and hypertension.  Some dogs and cats with CKD 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 "situational hypertension."   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 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 has high blood pressure that requires treatment.  In some cases, measurement of blood pressure taken at home can help determine if hypertension is present.  In any case, it is important to establish whether a dog or cat with CKD 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 decreased ability to produce erythropoietin and stimulate red blood cell production.  If CKD patients become anemic, additional drugs such as darbepoetin, that stimulate red blood cell production in the bone marrow may be used.  In addition, to this erythroid stimulating agent, drugs to enhance the action of the body’s own erythropoietin, known as hypoxia-inducible factor prolyl hydroxylase inhibitors, may be prescribed by your veterinarian.  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 (i.e., Diplomates of the American or European Colleges of Veterinary Internal Medicine) or specialists in nephrology (i.e., Diplomates of the American College of Veterinary Nephrology and Urology) in conjunction with owners who understand the potential complications of such treatment.

In some instances, caregivers can be taught to administer electrolyte-containing fluids subcutaneously (i.e., under the skin) to their cats or small dogs with CKD when the animal is not eating and drinking enough to maintain their 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 CKD, a long-term feeding tube can be placed in the esophagus (i.e., esophagostomy or e-tube tube) that will allow the owner to easily administer liquified food, water, and medications.  These e-tubes can be tolerated amazingly well by many cats with CKD and may stay in place for months, if not for years.  Although there is a small learning curve, e-tubes greatly facilitate the caregiver’s ability to administer food, water, and medications in a way that is not stressful to the cat.

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