Dogs and cats and kidney failure

 

Kidney failure... kidney disease in the dog and cat is a common and difficult disorder to manage.  Often called CRF... Chronic Renal Failure, it is seen most often in the older dog or cat. Kidney failure has it origins in a wide variety of causes.  For example, some animals are born with poorly constructed or functioning kidneys and never reach totally optimum health.  Eventually, these individuals usually fall into kidney failure at an early age.  Another type of kidney failure can occur after accidental ingestion of antifreeze that contains ethylene glycol.  These situations cause sudden and often irreversible renal (kidney) failure. Quite commonly, kidney failure results from low grade, long term (chronic) inflammation of kidney tissues called chronic nephritis; the damage caused by this inflammation renders permanent damage to delicate renal tissues that are not able to repair themselves or heal as some other body tissues do.  Eventually, not enough normal functioning tissue remains to support the body's need for metabolic regulation and waste elimination. The dog or cat becomes UREMIC, a condition where body waste material builds up in the blood. These toxins promote vomiting, poor appetite, depression, and eventually death.  Bacterial invasion of the kidneys is a common cause of chronic nephritis and kidney failure. 

NORMAL KIDNEY PHYSIOLOGY
The nephron is the structural and functional unit in the kidney. A nephron consists of a glomerulus in a capsule, proximal convoluted tubule, loop of Henle, and distal convoluted tubule which leads to a collecting duct.  The collecting duct empties into the renal pelvis.

Normal kidney function involves the following responsibilities, among others:
1.)  Regulating the amount of fluid in the spaces surrounding the body's cell.  This is called extracellular fluid volume regulation.
2.)  Regulating the amounts and types of solids in the blood in order to keep blood concentration within normal limits.  This is called blood osmotic pressure regulation.
3.)  Regulating the acid-base balance of the animal through retention or elimination of specific ions in the blood.  Common important ions affecting the acid-base balance of dogs and cats are bicarbonate, sodium, ammonium, potassium and hydroxyl ions.  This function keeps the pH (amount of acidity) of the blood and body fluids within strict normal ranges.
4.)  Removing metabolic waste products such as uric acid and also molecular foreign substances detoxified by liver.
5.)  Reacting to Aldosterone (ADH) produced in the adrenal glands. The major target of aldosterone is the distal tubule of the kidney, where it stimulates exchange of sodium and potassium and the reabsorption of water back into the blood.
6.)  Production (Erythropoetin), a chemical effecting red blood cell production.

The kidneys receive about 20 percent of  the heart's blood output and play a vital role in keeping the dog or cat in normal metabolic balance. The glomerular blood vessels have a large endothelial surface which allows for the active and passive transport of many chemicals into and out of the kidneys. 

KIDNEY STRUCTURE
The functional unit of the kidney... the real mechanism whereby the kidney does most of its prescribed tasks, is called the NEPHRON.  The nephron is a delicate, structurally complicated, microscopically small collection of tiny tubes, capillary beds that have distinct and different blood pressure settings at two locations along the tubes, and cell membranes that have precise tasks to perform.

Glomerulus... is a ball of capillaries with a large surface area at which multiple interchanges of fluids and dissolved elements occurs.
Bowmans Capsule... is the proximal end of a tubule that surrounds glomerulus.
Proximal convoluted tubule... leads to what is called the Loop of Henle that is situated in the medullary area of the kidney.  There is an ascending limb and a descending limb, each of which has particular and unique functions.
Distal convoluted tubule... leads into collecting ducts.
Pelvis... is an enlargement at the distal end of the collecting ducts that provides a common area of urine collection before the urine passes down the ureter into the bladder.

CORTEX The glomeruli are found in the outer area of the kidney called the cortex. Each glomerulus is surrounded by a "Bowman's Capsule". Most of the fluid that passes into the Loop of Henle in the cortex is reabsorbed in the medulla back into the blood.

TREATMENT FOR KIDNEY FAILURE
In human medicine, dialysis and kidney transplantation are the main methods of dealing with advanced kidney failure.  Expensive and time consuming, these methods are also employed in treating dogs and cats but impose heavy financial and time burdens on the pet owner and some stress on the patient who is already stressed by the disease.  Unfortunately, once the diagnosis of kidney failure is made, most patients are so sick that response to treatment is unrewarding and slow.  The pet's owner may need to consider euthanasia in order to prevent the long, slow, and agonizing death that comes from complete renal shutdown.  In very extreme and special circumstances, a kidney transplant may be an animal's only hope of long term existence.  

Kidney transplantation is a controversial topic but the science and success rate in cats and dogs has advanced greatly in recent years.Treating kidney failure is one of the most consistently discouraging aspects of veterinary medical practice.  The difficulty stems from the fact that once a dog or cat has lost 75% of total renal function, the ability to remove metabolic waste products is outweighed by the buildup of those toxins.  The animal is simply not able to keep up with the "housecleaning"  and as a result gradually becomes increasingly more toxic.  Body chemistry swings more and more acidic, important chemicals and nutrients are lost from the body and the animal comes gradually closer and closer to a fatal uremic poisoning.  In some cases, gradual kidney tissue loss can be present for years before the patient becomes critical and actual "renal failure" is diagnosed. The goal of treatment is to allow the patient to live as close to a normal life as possible under the circumstances.  Since the kidneys do not heal or regenerate new and functioning tissue, the remaining functional tissue carries the entire burden normally handled by two healthy kidneys.  Intravenous and subcutaneous fluids can be administered for varying lengths of time to try to correct acid-base imbalances.  Vomiting can be controlled.  Anti-ulcer medication can be given. Bicarbonate may be administered either orally or intravenously to assist in neutralizing acid buildup.  B-vitamins are provided. 

Antibiotics are employed if there is an infection present anywhere in the body... taking into consideration that some antibiotics will also build up in the patient if renal function is compromised.  Phosphate binders and Omega Fatty acids in correct amounts and proportions may be temporarily beneficial for the Chronic Renal Failure patient.  High quality, low protein diets have been proven to be helpful in lessening the metabolic tasks that must be performed by the kidneys once end stage kidney disease is present.

DIETARY CONSIDERATIONS

Contrary to popular myth, diets rich in protein ("high protein levels") do not cause kidney damage.  Research done decades ago indicated that rodent kidneys were adversely affected by diets high in protein... and misguided researchers extrapolated that data to apply to the canine. There is no evidence that feeding dogs and cats diets rich in or "high" in protein actually causes kidney damage or disease.  Some day this myth will be finally be put to rest.  In fact, there is ample research and well documented studies that prove that dogs and cats thrive on diets with levels of protein consistent with a meat-eater's (carnivore) natural prey selection. Additionally, documented research on dogs indicates that reducing dietary protein levels in older dogs may be unwise; however, if kidney damage is already present to the extent that the BUN levels are 75mg/dl or above, some restriction of dietary protein may be beneficial for metabolic reasons... not renal reasons.  "...restriction of protein intake does not alter the development of renal lesions nor does it preserve renal function." (See KIRKS VETERINARY THERAPY XIII, Small Animal Practice, W. B. Saunders, page 861).  Restricting dietary protein may be helpful to those patients whose BUN levels are rather high and that are already in advanced kidney failure.

MEDULLA
The medullary area of the kidney is fed by tiny arterioles.  Any damage to glomeruli affecting efferent arteriolar blood flow will also cause damage in the tubules located in the medulla. Anything that adversely impacts the blood flow through the medulla can have serious consequences for the tubular structures.  The medulla is slightly less vascular than the cortex.  The renal tubules that make up most of the medullary tissue have high metabolic rates and therefore high nutritional requirements.   Tubules are responsible for water loss and conservation.  Filtered water containing waste products (urine) are passed into the renal pelvis and then on into the ureter.  In addition to waste management the renal medulla assists in regulation of blood pressure, the elimination of toxins and the production of hormones such as erythropoietin.

PELVIS
The renal pelvis collects the kidney filtrate and funnels the urine fluid into the ureter that leads to the bladder.  The pelvic area of the kidney often is the site of kidney stones and can be a reservoir of infection once micro organisms reach this area of the kidney. 

CAUSES OF KIDNEY FAILURE
A partial list of causes of kidney failure include:

DIETARY CONSIDERATIONS
Contrary to popular myth, diets rich in protein ("high protein diets") do not cause kidney damage.  Research done decades ago indicated that rodents were adversely affected by diets high in protein and misguided researchers extrapolated that data to apply to the canine

HEREDITARY/CONGENITAL ABNORMALITIES:
These types of kidney disease are very frustrating to try to control of repair.  Most dogs and cats with abnormally constructed kidneys will develop kidney failure and do not live anywhere near a normal life span.   Ultrasound evaluation, clinical tests and contrast x-rays (Urography) are needed to make a correct diagnosis of the type of Inherited/Congenital disorder that may be present.
Polycystic kidney disease (PKD) is not very common and creates cystic areas in the kidneys where normal function and structure are lost.  Eventually, even if the dog or cat reaches maturity, gradual increases in metabolic waste products and signs of kidney disease prevent optimum quality of life and the animal dies or is mercifully euthanized. Polycystic Kidney Disease is an inherited kidney disease that has been found in Persian/Exotic cats.  In dogs, Bull Terriers may be affected more commonly than other breeds
Familial glomerulonephritis in the Bernese mountain dog.
Hereditary nephritis in the Bull Terrier.
Renal agenesis, also called kidney aplasia, occasionally occurs and the individual is born with one or both kidneys not present.  Dogs, cats and humans can survive quite well if one normal kidney is present and functioning. 
Renal hypoplasia is a condition where the kidney(s) do not develop completely.  This is seen in German Shepherds and other breeds. 
Renal cortical hypoplasia is a condition where the cortex of the kidney(s) develops incompletely. 
Renal dysplasia is a condition where the kidneys develop abnormally. Renal failure develops with protein loss in urine.
Renal tubular dysfunction occurs when the filtering tubules of the kidneys do not function properly. In Basenjis, glycosuria develops and is called Fanconi syndrome.amilial glomerulonephritis in the Bernese mountain dog.
Hereditary nephritis in the Bull Terrier.
Renal agenesis, also called kidney aplasia, occasionally occurs and the individual is born with one or both kidneys not present.  Dogs, cats and humans can survive quite well if one normal kidney is present and functioning. 
Renal hypoplasia is a condition where the kidney(s) do not develop completely.  This is seen in German Shepherds and other breeds. 
Renal cortical hypoplasia is a condition where the cortex of the kidney(s) develops incompletely. 
Renal dysplasia is a condition where the kidneys develop abnormally. Renal failure develops with protein loss in urine.
Renal tubular dysfunction occurs when the filtering tubules of the kidneys do not function properly. In Basenjis,

glycosuria develops and is called Fanconi syndrome.

FUNGAL INFECTIONS:
Rare Systemic fungal infections such as Blastomycosis, Coccidioidomycosis , and Histoplasmosis can attack nearly any tissue or organ in the body.  Systemic fungal infections are notoriously tricky to diagnose and treatment can be a challenge.  Permanent damage to renal tissues can be a sequel to any systemic fungal infection.  Most systemic fungal diseases are rather geographically oriented.

TRAUMA TO KIDNEY TISSUES:
Direct trauma to the kidneys can result in kidney failure.  Although rare, dogs and cats that are run over by vehicles can suffer permanent and irreparable kidney trauma.  Also, sudden physical shock to the kidney tissues from being struck by vehicles, baseball bats, kicking, or falls from a height, etc. can result in suffusive bleeding into the kidney tissue and permanently impair renal function.

BLOCKAGE OF URINE FLOW:
The most notable condition seen in cats and dogs from blockage of urine flow from the kidneys involves kidney stones or bladder stones or urethral obstruction.  These mineral concretions (usually called struvite uroliths) can form in the urine of the kidney pelvis or bladder and remain for long periods of time without causing serious trouble.  Easily contaminated with bacteria, however, urinary calculi are a major nidus of bacterial proliferation and will cause physical irritation to the kidney or bladder tissues.  These irritated tissues become thickened, scarred and prone to chronic infection.  Under certain circumstances a kidney stone can become lodged in the ureter leading away from the kidney toward the bladder and obstruct urine flow from the kidney.  If the situation persists for days the increased back pressure on the affected kidney will permanently damage kidney function and cause what is termed  hydronephrosis... a kidney swollen under pressure with backed up urine.  Surely this is a life threatening situation.  Generally this will occur in a single kidney and if only one kidney is damaged and the opposite kidney is normal, bodily waste removal needs can be met by the single remaining kidney. 

FUS (Feline Urological Syndrome) also sometimes called FLUTD (Feline Lower Urinary Tract Disease) has as one of its presenting emergencies a situation where mineral deposits obstruct the male cat's penis.  The bladder eventually dilates maximally and back pressure into the kidneys can cause death or permanent kidney damage if relief isn't provided expeditiously.  

Dogs with bladderstones often obstruct when a stone passes from the bladder but cannot be voided past the os penis... the bone present in the male canine's penis.  There is an inherent lack of room for the urethra to dilate in the area of the os penis and small bladder stones often dam up the urine flow at this site.  Surgical intervention is often required in these emergency urinary tract blockage cases.

Tumors, cysts, abscesses and scar tissue, if present in critical areas of the urinary tract, can create obstructive situations where the urine flow from a kidney is compromised.  Any situation that creates urine outflow restriction from a kidney will result in damage to delicate kidney tissue structures, and the damage is often permanent.  If enough tissue is destroyed or its function impaired, kidney failure will result.

CANCER:
Cancer of the kidney is extremely rare in dogs and cats.  When it is seen it usually takes the form of secondary invasion of metastatic cancer originating in a distant tissue.  In cats and dogs with leukemia disorders, the kidneys can be infiltrated with neoplastic leukemic cells which can severely compromise renal function.  There is a form of leukemia in cats that targets the kidneys and crowds out normal kidney cells.

EXTERNAL TOXINS (INGESTED TOXINS):
One of the most devastating external toxins that causes kidney failure in dogs and cats is antifreeze that contains ethylene glycol.  It doesn't take much of this sweet tasting liquid to prompt crystals to form in the delicate tubules of the kidney's filtration systems.  Massive doses of Vitamin D can be nephrotoxic (poisonous to the kidneys), rodent poison such as D-Con can allow hemorrhaging into the kidneys, the Easter Lily plant can be toxic if ingested and heavy metal toxicity such as from lead, mercury, cadmium, and arsenic all pose a very real threat to kidney tissue. Other renal toxins include thallium and turpentine.  There is evidence that raisins/grapes can be nephrotoxic to dogs.

ENDOTOXINS:
Endotoxins are chemicals produced within the animal that are toxic.  The most common type is that group of poisons formed by certain types of bacteria.  Clostridia organisms are famous for causing tetanus.  Many bacteria produce toxins from their normal metabolic waste products  In others, when they die off they leave behind toxins that can have damaging effects on delicate body tissues such as kidney structures and heart valve tissues. 

Endotoxins can have systemic effects as well and play a role in triggering shock in an animal where blood pressure declines

MEDICATIONS:
Some types of medications can be nephrotoxic such as paracetamol (analgesic), amphotericin B (antifungal), adriamycin (doxorubicin) in cats, kanamycin (antibiotic), neomycin (antibiotic), polymyxin B (antibiotic), cisplatin (a cancer drug), penicillamine (chelating agent/immune modulator), Cyclosporine (immunosuppressive), amikacin (antibiotic), and radiographic contrast agents.   Especially in older pets, medication administration needs to be employed in the light of potential harmful effects on the patient. 

AUTOIMMUNE DISEASES:
Systemic Lupus Erythematosis  (SLE)... known as the great imitator, this disorder can be difficult to diagnose since it can manifest as a disease of the skin/mucous membranes/nails, kidney and/or joints.  As a consequence of the animal's adverse and abnormal immune response to its own body tissues and proteins, many organ sites can be affected, including the kidneys. As the kidneys filter the circulating blood the abnormal immune molecules are trapped in the glomeruli and blood vessels, causing the kidney to leak protein.  A condition called Glomerulonephritis is the result and all sorts of abnormal kidney function can occur due to the damaged glomeruli.

Amyloidosis: Although not proven to be a result of an autoimmune disorder, the deposition of protein called Amyloid can actually occur in any tissue of the body.  The kidneys are most commonly affected and since the protein deposition destroys normal function, renal amyloidosis can be particularly serious due to the fact that kidney tissue does not repair itself.  Amyloidosis is fairly common in Akitas and Chinese Shar Pei dogs and reported in Abyssinian, Siamese, and Oriental Shorthaired cats.  Usually present in middle or older dogs and cats, amyloidosis most often results from chronic inflammation, cancer or other diseases.

 

DIAGNOSIS OF KIDNEY FAILURE

One of the first signs an animal will show when beginning to be affected by kidney failure is an increased thirst.  Polydipsia is the term used for this situation where the animal needs to consume greater amounts of water than normal.  Increased toxins and other metabolic waste products triggers sensors in the brain that the blood is too concentrated and through a series of chemical reactions the animal may have a sense of dehydration... and drinks more water to alleviate this sensation.  Compounding this sense of dehydration is actual water loss through the kidneys above normal amounts due to the kidneys being inefficient in retaining water within the body.  The increased thirst/water intake (polydipsia) causes an increased urine flow... and the animal urinates more frequently and produces higher volumes of urine.  Called Polyuria, the increased urine output seems unintuitive if the animal is actually affected with kidney failure.  Many pet owners have been baffled when the veterinarian mentions that the patient may have early kidney failure.  They often respond "How can that be, its urinating a lot more than it usually does?"  What really is happening is that much more urine is being produced and eliminated however the urine is becoming more and more dilute; the urine is not bringing along all those toxins and waste products for removal from the body.  And certain substances that the kidneys are supposed to be conserving  and keeping in the body such as glucose and protein are inappropriately being lost in the urine.  Especially protein loss, called Proteinuria, contributes to the animal's weight loss, inability to perform normal metabolic chemical processes, tissue repair and energy metabolism.

Water soluble vitamins, such as the B-vitamins are washed out of the body with this polyuria and polydipsia and the animal suffers from hypovitaminosis.

In order to make a diagnosis of renal failure the veterinarian will need to check two

avenues of data gathering... a urine sample and a blood sample.  Checking one without the other may render a diagnosis less accurate.  

 

The Urine Sample The measurement (SpG) that indicates how concentrated the urine is compared to distilled water (SpG = 1.00) will display a dilute reading... actually, very close to distilled water.  Since the action of conserving water while allowing undesirable metabolites and toxins to remain in the urine is the job of the tubules in the kidneys, whenever the tubules are damaged water conservation is less efficient; therefore more water flows through the tubules unresorbed and washes away in the now dilute urine.  Most cases of kidney failure display a SpG of about 1.008 to 1.012.  Generally, a normal dog's urine SpG will be 1.020 to 1.040; generally a cat's urine SpG will be about 1.025 to 1.050.  If a water deprivation test is done, where the animal has no access to water for 18 hours, the urine specific gravity goes up... the urine becomes more concentrated.  (Generally, if kidney failure is suspected a water deprivation test is not done because it will render the patient even more toxic.)

Many cases of kidney failure also show protein or sugar in the urine where in most normal animals urine protein is scarce and no glucose is present.  The loss, or lack of reabsorption of protein or sugar molecules back into the blood after an initial pass into the tubular fluid, places the animal in a negative protein/energy balance.  This state shows up as weight loss and muscle wasting.  And since these patients have a poor appetite, the added stress of protein and energy loss in the urine really tends to make the maintenance of normal body weight nearly impossible.

Bacteria and blood may show up in the urine samples of chronic renal failure patients.  Infectious agents, red and white blood cells, epithelial cells from the lining of the kidney and bladder structures, crystals, and protein plugs called casts that arise from damaged tubules all may be commonly observed in urine samples.  Conversely, some patients have such dilute urine and such thirst that a urine sample may have no detectable cells or debris but simply show a low Specific Gravity and very dilute urine.

THE BLOOD SAMPLE 
When renal function is diminished, many, many toxic chemicals build up in the patient's body.  Think of the situation as you would if there were no chimney on a factory and all those burned gasses and chemicals stayed within the walls of the factory.  That's just what happens when kidney failure is present.  In many patients, slow and progressive loss of filtering tubules creates a situation where these toxins very gradually build up; in other acute kidney diseases (such as anti-freeze poisoning) the sudden and massive damage creates immediate toxin buildup within the body.  Many dogs and cats become accustomed to very gradual toxin buildup as slowly progressive kidney disease moves toward the critical limit where there are not enough healthy nephrons to eliminate waste products.  Eventually, outward signs of kidney disease becomes evident.

Two of the most useful chemicals that veterinarian measure to see if toxins are building up in the patient's body are Blood Urea Nitrogen (BUN) and Creatinine.  Normal BUN levels in dogs and cats seldom reach higher that 25 to 30 mg/dl. (Mg/dl means milligrams of material per 100 milliliters of blood.)  Many patients presented in renal failure have BUN levels of 90 or higher!  Similarly, Creatinine, a  chemical normally present in the blood at levels less than 1.0 mg/dl, may rise to over 8 mg/dl.  Blood urea nitrogen (BUN) and Creatinine (a normal product of muscle tissue breakdown) are just two of many chemicals in the blood that are affected by kidney failure. Most veterinarians can check these two chemicals in the animal hospital; otherwise blood samples are sent to a veterinary lab for analysis and the results are faxed or called in to the referring veterinarian.

The diagnosis of kidney failure is made only after...
*  A thorough physical exam
*  A thorough discussion with the owner about the dog or cat's relevant history
*  A urinalysis is performed
* A blood chemistry analysis is performed 

 

TREATMENT FOR KIDNEY FAILURE
In human medicine, dialysis and kidney transplantation are the main methods of dealing with advanced kidney failure.  Expensive and time consuming, these methods are also employed in treating dogs and cats but impose heavy financial and time burdens on the pet owner and some stress on the patient who is already stressed by the disease.  Unfortunately, once the diagnosis of kidney failure is made, most patients are so sick that response to treatment is unrewarding and slow.  The pet's owner may need to consider euthanasia in order to prevent the long, slow, and agonizing death that comes from complete renal shutdown.  In very extreme and special circumstances, a kidney transplant may be an animal's only hope of long term existence.  Kidney transplantation is a controversial topic but the science and success rate in cats and dogs has advanced greatly in recent years.

Treating kidney failure is one of the most consistently discouraging aspects of veterinary medical practice.  The difficulty stems from the fact that once a dog or cat has lost 75% of total renal function, the ability to remove metabolic waste products is outweighed by the buildup of those toxins.  The animal is simply not able to keep up with the "housecleaning"  and as a result gradually becomes increasingly more toxic.  Body chemistry swings more and more acidic, important chemicals and nutrients are lost from the body and the animal comes gradually closer and closer to a fatal uraemic poisoning.  In some cases, gradual kidney tissue loss can be present for years before the patient becomes critical and actual "renal failure" is diagnosed.

The goal of treatment is to allow the patient to live as close to a normal life as possible under the circumstances.  Since the kidneys do not heal or regenerate new and functioning tissue, the remaining functional tissue carries the entire burden normally handled by two healthy kidneys.  Intravenous and subcutaneous fluids can be administered for varying lengths of time to try to correct acid-base imbalances.  Vomiting can be controlled.  Anti-ulcer medication can be given. Bicarbonate may be administered either orally or intravenously to assist in neutralizing acid buildup.  B-vitamins are provided.  Antibiotics are employed if there is an infection present anywhere in the body... taking into consideration that some antibiotics will also build up in the patient if renal function is compromised.  Phosphate binders and Omega Fatty acids in correct amounts and proportions may be temporarily beneficial for the Chronic Renal Failure patient.  High quality, low protein diets have been proven to be helpful in lessening the metabolic tasks that must be performed by the kidneys once end stage kidney disease is present.

DIETARY CONSIDERATIONS
Contrary to popular myth, diets rich in protein ("high protein levels") do not cause kidney damage.  Research done decades ago indicated that rodent kidneys were adversely affected by diets high in protein... and misguided researchers extrapolated that data to apply to the canine. There is no evidence that feeding dogs and cats diets rich in or "high" in protein actually causes kidney damage or disease.  Some day this myth will be finally be put to rest.  In fact, there is ample research and well documented studies that prove that dogs and cats thrive on diets with levels of protein consistent with a meat-eater's (carnivore) natural prey selection.  Additionally, documented research on dogs indicates that reducing dietary protein levels in older dogs may be unwise; however, if kidney damage is already present to the extent that the BUN levels are 75mg/dl or above, some restriction of dietary protein may be beneficial for metabolic reasons... not renal reasons.  "...restriction of protein intake does not alter the development of renal lesions nor does it preserve renal function." (See KIRKS VETERINARY THERAPY XIII, Small Animal Practice, W. B. Saunders, page 861).  Restricting dietary protein may be helpful to those patients whose BUN levels are rather high and that are already in advanced kidney failure.



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