Chronic Kidney Disease and Failure (CKD, CRF, CRD)
Chronic kidney disease is defined as kidney disease that has been present for months to years. Chronic renal disease (CRD), chronic renal failure (CRF), and chronic renal insufficiency refer to the same condition.
CKD is not a single disease. There are many different causes of CKD but by the time the animal shows signs of kidney disease the cause may no longer be apparent. Some potential causes of CRF include:
- congenital malformation of the kidneys (birth defects)
- chronic bacterial infection of the kidneys with or without kidney stones (pyelonephritis)
- high blood pressure (hypertension)
- diseases associated with the immune system (e.g. glomerulonephritis, systemic lupus))
- acute kidney disease, for example poisoning with antifreeze, that damages the kidneys can lead to CKD
Often the cause of CKD is unknown.
Structure of the kidneys
The microscopic unit of the kidney is called the nephron. Each kidney contains thousands of nephrons. When the pet is young and healthy not all nephrons are working all of the time; some nephrons are held in reserve. As the animal ages or if the kidneys are damaged, some nephrons die and other resting nephrons take over the work of those that die. Eventually all the remaining nephrons are working. When there are no extra nephrons remaining and kidney damage continues the pet will start showing signs of CKD. Because of this stepwise loss of nephrons the kidneys are able to "hide" the fact that they are damaged until the damage is severe. When 2/3 of the nephrons have been lost the pet is no longer able to conserve water and the pet passes larger amounts of dilute urine. By the time a pet has an elevation in the waste product creatinine in its blood, 75% of the nephrons in both kidneys have been lost.
What do the kidneys do?
When blood flows through the kidneys, the kidneys act as a complex filter that removes from blood wastes that are generated from break down of food, old cells, toxins or poisons and many drugs that are given for treatment of other diseases. The wastes are removed with water as urine. Waste products than can be measured in the blood include creatinine and urea nitrogen but there are many other waste products that are not measured by blood tests. The kidneys also acts as a filter to keep "good" substances in the blood. The kidneys regulate the amount of water in the blood by excreting extra water and retaining water to prevent dehydration by varying the amount of urine that is produced. The kidneys help regulate blood pressure by saving or eliminating sodium based on how much sodium the pet is eating. The kidneys help regulate calcium and vitamin D which keep bones strong. The kidneys produce a substance that helps with the creation of new red blood cells. Because the kidneys have so many functions, when the kidneys are not working normally, there are many signs that the pet may show.
CKD is progressive
By the time the pet shows signs of CKD, the damage is severe. There is no cure for CKD. The remaining nephrons are working so hard that with time they will fail as well. CKD is usually fatal in months to years but various treatments can keep the pet comfortable and with a good quality of life for months to years.
Signs of CKD
Because the kidneys perform so many functions, the signs pets with CKD show can vary quite a bit. The signs may be severe or may be subtle and slowly progressive. Despite the chronic nature of the disease, sometimes signs appear suddenly. Some of the more common signs of CKD include:
- drinking too much (polydipsia) and urinating large volumes of urine (polyuria)
- the increased volume of urine in the bladder may lead to, or worsen incontinence (leaking urine), especially at night
- vomiting and/or diarrhea
- lack of appetite and weight loss
- general depression related to the elevation of waste products in the blood
- anemia resulting in pale gums and weakness due to a low blood count
- overall weakness from low blood potassium
Less common signs include
- weakened bones can result in bone fractures
- high blood pressure can lead to sudden blindness
- itchy skin from calcium and phosphorous depositing in the skin
- bleeding into the stomach or gut or bruising of skin
Signs you may see if you examine your pet include: dehydration, weight loss, pale gums and ulcers in the mouth.
The signs seen in pets with CKD and the findings on examination are not specific for CKD and may be seen with many other diseases so blood and urine tests are needed to make a diagnosis of CKD.
Abnormalities that are often seen on diagnostic blood and urine tests include:
- anemia without signs of a response by the body to the low blood count (non regenerative anemia)
- increased wastes that are normally removed by the kidneys (blood urea nitrogen [BUN] and creatinine)
- increased phosphorus
- calcium is often normal but can be elevated in some pets with CKD and rarely is decreased
- dilute urine
- +/- protein or bacteria in the urine
Sometimes bruising occurs where the blood sample was drawn as pets with CKD may have platelets that are less sticky than normal (normal platelets prevent bruising).
A diagnosis of CKD can usually be made based on the signs, physical examination and blood and urine tests but other tests may be performed to look for an underlying cause for the CKD and/or to "stage" the CKD.
Details about Staging
The severity of chronic kidney disease (CKD) can be estimated based on blood waste product elevation and abnormalities in the urine such as the presence of protein. The International Renal Interest Society (IRIS) has developed a method to estimate the stages of CKD. Stages are numbered 1 through 4 where one is the least severe and four is the most severe. The higher the stage number also generally corresponds to the greater number of symptoms seen in the pet. Some treatments are recommended to be started when the pet has a certain stage of CKD.
Other tests that may be performed include
- Determination of kidney size using abdominal radiographs (x-rays) or ultrasound
What might this test show? The kidneys in pets with CRD are usually small reflecting the death of a large number of nephrons. If the kidneys are large then certain causes for the CKD should be considered such as lymphoma (cancer) of the kidneys, or an uncommon disease called amyloidosis. Some pets with signs of kidney disease who have large or normal sized kidneys may have acute kidney failure rather than CKD. The treatment and prognosis for pets with acute kidney disease differs from the treatment and prognosis of pets with CKD.
- Kidney biopsy
What might this test show? A biopsy is not required to make a diagnosis of CKD but the results of a biopsy may show a cause for the CKD. A biopsy is more likely to show specific information when the kidneys are big rather than small. A biopsy can be valuable in pets who develop CKD at a young age or who are of a breed known to develop congenital kidney disease. There may be specific microscopic changes in a kidney biopsy from an animal with congenital kidney disease that may suggest that related animals are also at risk for developing CKD. Knowledge that the cause of CKD is caused by congenital kidney disease does not change the treatment of the affected animal but does provide information for related animals, for example if you should remove them from a breeding program. When a biopsy is planned, usually the biopsy is collected using ultrasound or laparoscopy to see the kidney during the biopsy so that no other organs are damaged during the biopsy.
- Bacterial culture
What might this test show? Bacterial infection is not a common cause of CRD but pets with CKD may develop a bacterial infection as several aspects of the pet's immune system may be less functional when the kidneys are failing. If white blood cells are observed on microscopic examination of the pet's urine, a bacterial culture of the urine should be obtained.
- Tests of clotting ability
What might this test show? If a pet is going to under go kidney biopsy, tests may be performed in advance to evaluate the ability to stop the bleeding from the biopsy site.
Treatment of CRF
The severity of the pet's signs will determine what treatments are needed. Not all treatments presented below may be needed or appropriate for each pet with a diagnosis of CKD. Treatments may also be started incrementally (a few treatments are started and then based on patient response, additional treatments may be added later). The information below is not meant to be a substitute for veterinary care.
Pets with severe signs may be hospitalized for fluid and intravenous drug treatment to reduce the amount of waste products in their body. Many pets with CKD will feel better in response to treatment with IV fluids but if the kidney disease is extremely severe the pet may not respond to treatment.
Those pets who are still eating and not showing severe signs are treated with a variety of treatments, often introducing treatments incrementally as new signs develop. The treatment approach is often called "conservative" compared to more aggressive treatments such as hospitalization for fluid therapy, dialysis or kidney transplantation. Remember that CKD is not a disease that can be cured. Treatments are designed to reduce the work the kidneys need to perform, to replace substances that may be too low (such as potassium) and to reduce wastes that accumulate such as urea (generated by the body from proteins) and phosphorus. The initial response to conservative therapy may be relatively slow, taking weeks to months to see a response.
Feeding of a kidney diet is usually recommended. Kidney diets contain less protein compared to other diets and the protein is high in quality. It is protein in the diet that is converted to waste products that the kidneys must remove in the urine. The higher the quality of the protein in the diet, the less wastes created for the kidneys to eliminate. Low quality protein requires the kidneys remove more wastes. which makes them work harder. Egg and meat contain higher quality protein; cereal grain protein is of lower quality which leads to more wastes for the kidneys to eliminate. Protein is used by the body to repair cells and tissues that are continually regenerating, so a pet needs some protein in their diet. By feeding a low quantity, but high quality protein diet that contains an appropriate amount of fats and carbohydrates, the pet's body can use the protein for replacing the cells and tissues and use the fat and carbohydrates for energy. Kidney diets also contain a lower amount of phosphorus. Phosphorus accumulates in the blood when the kidneys are diseased. Kidney diets control the amount of other substances that may be too high or too low in patients with CKD such as salt, potassium, magnesium and B vitamins. There are differences in the kidney diets for dogs and cats. When making diet changes it is often beneficial to gradually introduce the new diet by adding increasing amounts of the new diet while reducing the amount of the current diet over 1 to 2 weeks. The pet is more likely to accept a new diet when it is introduced gradually and it is less stressful to the kidneys to gradually adapt to changes in the diet.
Protein restricted diets are less palatable than higher protein diets. Pets with CKD that are still eating are more likely to accept a change in diet to a protein restricted diet than are pets who are very ill and refusing most foods. Protein restricted diets are more expensive than higher protein diets.
There are many pet food companies that sell kidney diets. Homemade diets can be fed but it is best to work with your veterinarian to formulate a diet that is balanced.
It is generally agreed that feeding renal failure diets to dogs and cats with kidney disease improves their quality of live and may minimize the progression of the disease resulting in a longer life span. Studies that evaluate the effect of dietary changes on quality and quantity of life typically use commercial diets that differ in their composition of protein, phosphorus, sodium and lipids compared to maintenance diets so that positive effects are not attributable to a single component of the diet but rather to a "diet effect".
A randomized, double masked, clinical study in 38 dogs with spontaneous stage 3 or 4 kidney disease, half of which were fed a kidney failure diet and the other half a maintenance diet, published in JAVMA in 2002, demonstrated improved quality and increased quantity of life in the group fed the renal failure diet.
- The median interval before development of a uremic crisis was twice as long in the group fed the renal diet
- Dogs fed the renal diet survived at least 13 months longer (average 593 vs 188 days)
- Owners of dogs fed the renal diet reported significantly higher quality of life scores for their dogs
The results of a study of cats with naturally occurring stable chronic renal failure fed a diet restricted in phosphorus and protein compared to cats with CKD fed a maintenance diet reported a median survival of 633 days for 29 cats fed the renal diet compared to 264 days for 21 cats fed a regular diet. The groups were not randomly determined but based on cat & owners willingness to change to the renal diet.
In a study published in JAVMA in 2006, 45 client-owned cats with spontaneous stage 2 or 3 CKD were randomly assigned to an adult maintenance diet (23 cats) or a renal diet (22 cats) and evaluated for up to 24 months. Findings included:
- Significant differences: BUN lower and blood bicarbonate higher in the renal diet group
- No Significant differences
urine protein-to-creatinine ratio
parathyroid hormone concentrations.
- 26% of cats fed the maintenance diet had uremic episodes (26%), compared with 0% cats fed the renal diet
- At the conclusion of the study, 5 (21.7%) cats in the maintenance diet group had died from renal causes and there were no renal-related deaths in the renal diet group.
- There were no significant differences in quality of life as perceived by owners responding to a questionnaire.
- Owners impressions of cats willingness to consume the diets did not differ between groups
Because pets with kidney disease cannot conserve water by making concentrated urine, their water intake is very important to prevent dehydration. Make sure they always have plenty of fresh water available. If the pet is not eating well, or is vomiting, then s(he) may not be drinking enough and may get dehydrated. Pets can be encouraged to drink by giving them flavored broths in addition to plain water. The broth should be low in sodium and its best to discuss with your veterinarian other ingredients in the broth to make sure it doesn't contain substances that will make the kidneys work harder.
Water soluble vitamins like B and C are lost in greater amounts when the pet is urinating greater amounts. Kidney diets contain increased amounts of water soluble vitamins so additional vitamins do not need to be given unless a homemade diet is being fed.
Lack of appetite and increased loss of potassium in urine may result in low body potassium (hypokalemia). Cats with CKD are more likely to have low body potassium than are dogs. Cats with low potassium may develop painful muscles. Both cats and dogs may be weak when potassium is low. Cat kidney diets contain higher levels of potassium so additional supplementation is probably not needed unless the cat shows signs of muscle pain. Potassium gluconate or citrate can be given by mouth if potassium supplementation is needed. Potassium chloride is acidifying and is not recommended.
Phosphorus, calcium and PTH
Pets with CKD usually have increased blood phosphorus. In health, phosphorus and calcium are controlled by a hormone called parathyroid hormone (PTH). PTH works with vitamin D on the intestine, kidney and bone to keep calcium and phosphorus normal. As the kidneys fail the amount of PTH in the body is elevated and the amount of vitamin D is reduced. Elevated PTH itself may be responsible for some of the signs shown by pets with CKD. PTH draws calcium and phosphorus from the bones which can weaken bones which can lead to bone fracture.
Kidney diets typically contain reduced phosphorus and an appropriate amount of calcium but if phosphorus remains elevated when the pet is eating a kidney diet then phosphorus can be tied up in the intestinal tract so it can be eliminated in the stool. Intestinal phosphate binding agents include aluminum carbonate, aluminum hydroxide, aluminum oxide, calcium citrate, calcium acetate and calcium carbonate and sevelamer hydrochloride. Phosphate binding agents which contain calcium should not be used until blood phosphorus is normal to prevent calcium and phosphorus from combining and precipitating in tissues including the kidneys. It is not usually necessary to give additional calcium but if a pet has low blood calcium, the phosphorus should be normalized before giving calcium. Even when blood phosphorus is normalized, PTH levels are still higher than normal. The administration of low doses of vitamin D (1, 25 dihydroxycholecalciferol [calcitriol]) will suppress PTH and possibly slow the rate of progression of kidney deterioration.
It is not 100% agreed that giving your pet calcitriol will slow the deterioration of the kidneys.
Some pets with CKD will have an acid blood pH. Kidney diets are designed to counteract the acidosis but very sick animals that are hospitalized may need addition treatment to correct the acidosis.
Diseased kidneys are less efficient at regulating sodium and sodium in turn helps control blood volume and pressure. Excess sodium can lead to water retention and not enough sodium can lead to dehydration. When changing diets that contain different amounts of sodium (kidney diets usually have less sodium than regular diets) make the change gradually over several weeks. Use caution when giving your pet table scraps or treats that may be high in sodium.
High blood pressure (hypertension)
Many pets with CKD have high blood pressure. High blood pressure can contribute to further decline of kidney function and can occasionally lead to sudden blindness from retinal detachment. Ideally blood pressure should be measured by your veterinarian and hypertension confirmed before giving drugs to treat high blood pressure but measuring true blood pressure in dogs and cats can be difficult. If the pet has an elevation in blood pressure it may be due to the excitement of being examined or due to CKD. The calmer you are able to keep your pet during examination, the more reliable the readings for blood pressure. There are several drugs that may be used to manage high blood pressure including enalapril, benazepril, or amlodipine (and others). Enalapril and benazepril are in a class of drugs called ACE inhibitors and are sometimes used in pets with CKD that have abnormal amounts of protein in their urine even when blood pressure is normal.
The kidneys play a role in producing a hormone called erythropoietin which stimulates the production of new red blood cells. Red blood cells live about a hundred days so new cells are continually being made. Less erythropoietin is made in pets with CKD leading to anemia. The packed cell volume (PVC) (also called hematocrit) is the percentage of blood cells compared to fluid in whole blood. When the PCV is ~20 in cats and ~ 25% in dogs, anemia may contribute to lack of activity and weakness.
Anemia can be treated by blood transfusion or by the administration of human erythropoietin. Erythropoietin is very effective in increasing PCV but because human erythropoietin is not exactly the same as dog and cat erythropoietin, over time, the pet may form antibodies that cause the medication to become ineffective. Canine and feline erythropoietin are currently being studied.
Certain types of fats (polyunsaturated omega 3 fatty acids) may slow the decline in kidney function are are often present in kidney diets.
Some cats and dogs with kidney disease may not drink enough to prevent becoming dehydrated and may benefit from the administration of intermittent SC fluids. If your veterinarian feels your pet may benefit from giving subcutaneous fluids.
Lack of Appetite
The accumulation of wastes in the body often decreases appetite. A goal of several of the above treatments is to reduce the amount of wastes in the blood. If the pet remains off food despite above treatments you might try different brands of renal failure diets, warming the food or adding odiferous toppings to entice the pet to eat.
Increased levels of waste products cause the pet to vomit. Your veterinarian may recommend medications that reduce nausea or act directly on brain centers to reduce the urge to vomit.
Drugs used to treat other diseases
Because the kidneys are responsible for elimination of many drugs, make sure that your veterinarian is aware of any other medications you are giving your pet as these may accumulate in the body to toxic levels if the kidneys cannot eliminate them.
If the urine shows signs of infection or if a urine culture grows bacteria then antibiotics may be administered. If a urinary tract infection is involving the kidneys, the period of treatment is much longer than a infection of the bladder.
You are in the best position to judge what is stressful to your pet. When a pet is stressed they may drink and eat less than normal. Reduced water intake is detrimental to diseased kidneys. When possible, keep your pet calm. That might mean for example: having an in-home pet sitter if your pet is stressed by boarding, removing the pet from the household during a party or limiting contact with other animals if these situations appear to be a source of stress for your pet. Extremes in heat or cold are stresses. Certain drugs such as prednisone/cortisone make the kidneys work harder.
There has been progress made in transplantation of kidneys, more for cats than for dogs.
See http://www.felinecrf.com/transb.htm for a list of facilities that currently offer transplanation.
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