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What is CRF?

Description of CRF (also called CRI, Chronic Renal Insufficiency)

Approximately 200,000 tiny structures (nephrons) in the kidneys eliminate waste products and regulate electrolytes in the body. CRF results when these nephrons begin to die off and waste products and electrolytes can no longer be processed effectively. The waste then accumulates in the cat's body. In effect, a cat in CRF is being poisoned by the waste that the kidneys are unable to filter. Electrolyte imbalances, anemia and blood pressure problems may also occur as the kidneys continue to deteriorate.

The Kidneys

The kidneys have five primary functions:
  • Filtering waste products from the body (primarily urea and creatinine).
  • Regulating electrolytes (potassium, calcium, phosphorus and sodium).
  • The production of erythropoietin, which helps to stimulate the bone marrow to produce red blood cells.
  • The production of renin, an enzyme that controls blood pressure.
  • Production and concentration of urine
Symptoms of CRF

CRF can only be accurately diagnosed with clinical tests. There are some symptoms and behaviors that indicate the likelihood of CRF and, if these are observed, the cat should be tested as soon as possible.

The most telling signs are increased thirst (polydipsia) and excessive urination (polyuria). As the condition progresses, your cat may experience loss of appetite, nausea and vomiting, weight loss, poor hair coat and emaciation. Only 30% of kidney capacity is needed for normal functioning. Therefore, no symptoms will be seen until approximately 70% of renal function is lost. It is important to begin treatment as soon as the first symptoms appear.


Even with diet control, drugs and fluid therapy, you will eventually see at least some of the symptoms on the following list. Not all cats will exhibit all symptoms.

  • Excessive urination
  • Increased thirst
  • Nausea and gagging
  • Licking lips
  • Grinding or cracking sound in jaw
  • Vomiting (both clear/foamy liquid and food)
  • Drooling
  • Dehydration
  • Hunching over the water bowl
  • Stomach irritation (uremic gastritis)
  • Constipation
  • Loss of appetite
  • Weight loss
  • Muscle wasting
  • Emaciation
  • Poor hair coat
  • Halitosis (ammonia smell)
  • Lethargy
  • Sensitivity to sound
  • Eating litter
  • Weakness
  • Depression
  • Oral ulcers
  • Detached retinae
  • Convulsion, low temperature, coma (end-stage)

Chronic vs. Acute Renal Failure

Renal failure may be either chronic or acute. Chronic Renal Failure (CRF) is a progressive, irreversible deterioration of kidney function. Because cats hide their illnesses and the very early signs of CRF are subtle, this disease may only be recognized when the patient reaches the 70% deterioration level and more dramatic symptoms are observable. The seemingly sudden onset may appear to be an acute condition but is most often a crisis point of CRF. By comparison, Acute Renal Failure (ARF) is characterized by an abrupt shutdown of kidney function, most often accompanied by oliguria (reduced urine production). The primary causes of ARF in cats are: urinary obstructions, infectious diseases, trauma, and the ingestion of toxins - the most common one being ethylene glycol which is contained in antifreeze. ARF is extremely serious and can quickly become fatal. Immediate veterinary treatment is imperative. Though the prognosis is usually poor, if damage has not been too severe and medical treatment is aggressive, it may be possible for normal kidney function to be restored.

Age-related Deterioration

CRF is one of the leading causes of illness and death in older cats. If your cat is age seven or older, it's a good idea to check for CRF during each annual exam, with a blood test, urinalysis and blood pressure measurement. With early detection, proper diet, and hydration, cats may remain happy and active for quite some time before the inevitable decline. See the Tests and Diagnostics section for more information on identifying CRF.

What Causes CRF?

CRF may have one or more causes. The common contributing factors are age, genetics, environment, and disease. In recent years, more attention has been directed towards high blood pressure, low potassium levels, acidified diets, and dental disease as possible contributors to the development of CRF. Research has indicated that some breeds have a higher rate of CRF than others. The Maine Coon, Abyssinian, Siamese, Russian Blue, Burmese, and Balinese appear to be more likely to develop CRF than other breeds. Although CRF can occur at any age, it is usually a disease of older cats. With dietary improvements in cat food, advances in feline medical care and more cats living indoors, cats are now living much longer and their bodies eventually wear out just as human bodies do.

Many renal diseases result in CRF. Usually the diagnosis in the vet’s office is simply CRF because the cause cannot be determined in most cases. Causes can, however, be divided into two groups – congenital and acquired. Congenital kidney disease may progress and turn into CRF in kittens and younger cats. We have listed some of the diseases and conditions that can cause CRF below with a very brief description. For additional information, see our Links Page under the section titled Other Kidney Disease Links.

Congenital kidney diseases:

    • Polycystic Kidney Disease (PKD) is inherited and is most common in Persians and crosses between Persians and Domestic Shorthairs. In PKD, normal kidney function is lost due to the development of cysts in the renal medulla and cortex. PKD can also be acquired rather than congenital.
    • Renal Aplasia occurs when one or both kidneys are not present at birth.
    • Renal Dysplasia occurs when one or both kidneys develop abnormally.
    • Renal Hypoplasia occurs when one or both kidneys have a decreased number of nephrons that work properly.

Acquired kidney diseases:

    • Amyloidosis occurs when amyloid, a protein substance, is deposited in the kidneys. Familial amyloidosis is common in Abyssinian cats and the cause is unknown.
    • Chronic Interstitial Nephritis is probably the most common cause of CRF in cats and it may be because it is often the end result of other kidney diseases. The kidneys become shrunken and normal kidney tissue turns into dead scar tissue.
    • Glomerulonephritis is an inflammatory disease resulting from an antigen-antibody reaction that damages the glomeruli.
    • Hydronephrosis occurs when an obstruction prevents normal urine outflow.
    • Pyelonephritis is a bacterial infection of the kidneys.
    • Renomegaly is the enlargement of one or both kidneys, caused by any number of conditions.

Because there is no single, overwhelming cause of CRF, there is no definitive protocol for CRF prevention at this time. Not all cats will develop CRF. Statistical studies give hints about what may be helpful. However, since there are several possible mechanisms that may cause the onset of CRF, attempts at prevention may not be efficacious.

Contributing Factors

Acidified Diet

There is speculation that acidified diets, commonly fed to cats with lower urinary tract disease, may reduce absorption of potassium and thus contribute to hypokalemia and either cause or aggravate metabolic acidosis.

Potassium Imbalance

Low potassium is a possible cause of CRF and, at the very least, may be an early warning sign. It has been suggested by some veterinarians that potassium supplementation should begin when the potassium level is on the low side of normal rather than waiting until it is below normal, the reasoning being that early potassium supplementation may delay the progress of CRF. Cats in renal failure are unable to prevent excessive potassium loss and the body will extract potassium from tissue to maintain blood levels, thereby masking the actual potassium deficiency as measured by a blood test. ALWAYS consult your vet when supplementing potassium, whether your cat is in the early, middle or end-stage of CRF. For additional information, including the dangers of both low and high potassium, see the Medications section of this site.

The Dental Connection

It is a good idea to have a mouth, teeth, and gum examination done during each annual examination. Just as in people, removal of tartar, teeth cleaning, etc. can be beneficial in keeping a cat healthy. The bacteria present in the mouth resulting from dental problems can certainly contribute to CRF. A significant percentage of the letters we've received from visitors to the Web site mention that CRF was diagnosed either just prior to or just after routine teeth cleaning or dental surgery.

The connection between dental procedures and the diagnosis of CRF may be the result of a number of factors.

  • The routine blood work done prior to or after dental surgery may reveal CRF that has been present in the patient for some time.
  • The anesthesia used during oral surgery could exacerbate existing CRF and cause the sudden appearance of symptoms. Be sure to request that any anesthesia be a type that does not tax the kidneys.
  • The oral surgery itself may endanger the kidneys by causing the release of bacteria and their toxins during the procedure. Talk to your vet about administering antibiotics for a time prior to dental work.

High Blood Pressure

The relationship between the kidneys and blood pressure is complex. The kidneys play a crucial role in regulating blood pressure. The kidneys are also subject to damage from high blood pressure. Further, high blood pressure, by forcing the nephrons to work at above their normal capacity, can mask CRF for a while. The increased pressure causes the nephrons to deteriorate more rapidly, thus accelerating the course of CRF.

Treatment for Hyperthyroidism

Hyperthyroidism is one of the most common diseases of cats, particularly middle-aged and senior cats. Hyperthyroidism increases the blood flow to the kidneys and may mask symptoms of CRF. Recent studies indicate that a significant percentage of cats who were treated for hyperthyroidism (whether the treatment was surgical, radiological, or a life-long prescription for Tapazole) showed symptoms of CRF. These treatments reduce the thyroid hormone in the cat's system. Among other things, this reduces the blood flow to the kidneys. CRF that had previously been masked becomes apparent. Sub-clinical kidney failure can become clinical and even healthy kidneys can undergo some deterioration.

It is crucial to monitor kidney function on a regular basis in cats who are being treated, or who have been treated for hyperthyroidism.

Links to additional information about the CRF/Hyperthyroidism connection in cats:
Changes in renal function in cats following treatment of hyperthyroidism using I131

Effect of treatment of hyperthyroidism on renal function in cats

Changes in renal function associated with treatment of hyperthyroidism in cats

Effects of methimazole on renal function in cats with hyperthyroidism

Diagnosis

There are several conditions, which exhibit symptoms similar to those seen in CRF. The only way to know for certain is to have your veterinarian perform some clinical tests. Urinalysis will be done to determine if the cat's urine is dilute; this indicates that the kidneys are not passing waste materials. Blood tests will determine the levels of creatinine and BUN (blood urea nitrogen) as well as other components of the blood. An elevated creatinine level is the most certain sign of loss of kidney function.

Treatment

There is no cure for CRF but the condition may be managed for a time. The cornerstone of CRF management is to control the amount of waste products that are sent through the kidneys. Since the remaining nephrons are limited in their ability to process waste, the idea is to reduce the amount of waste to a level that the nephrons can accommodate. This is done through a combination of diet, medication, and hydration therapy (diuresis).

There are current research projects targeted at slowing the progression of CRF with ACE inhibitors and calcium channel blockers. These medications dilate the blood vessels thereby decreasing blood pressure while facilitating a non-damaging increase in blood flow that doesn't tax the kidneys. The results so far have been encouraging, but the studies are not yet complete. Kidney transplantation and dialysis are also now possible. A kidney transplant should be viewed not as a cure, but as an option for the treatment of feline CRF. For more information on transplants, see the Transplant section of this site. For more information on dialysis, see the Dialysis subsection of the Management of CRF section.

Prognosis

CRF is a terminal disease. The only questions are how long and how well the patient will live until the end. With proper treatment, the cat may have from months to years of relatively high-quality life. As the cat's caregiver(s), it is up to you to determine when the quality of life has decreased to a point at which prolonging life no longer has value.

As CRF progresses and toxin levels rise, cats become more uncomfortable with an overall sensation of feeling unwell. Human patients with a similar condition don't report "pain" but describe their condition as feeling poorly. Dehydration, in particular, can make the patient very uncomfortable. Aggressively treating CRF, especially with subcutaneous fluid therapy, should not be thought of as "prolonging the agony" as there is no significant pain associated with kidney failure until the end-stage. Even then, unless the patient convulses, the chief symptoms will be malaise, weakness, nausea and discomfort.

CRF Research, Studies and News

Recently Developed Diagnostic Tools

E.R.D. HealthScreen Feline Urine Test
A urine test has been developed by Heska to detect the presence of microalbuminuria (small amounts of albumin) in feline urine. The presence of albumin in the urine is an indicator of glomerular damage associated with renal failure and/or other underlying conditions causing albumin to leak into the urine. This tool is the only test that will detect albumin leakage and may provide an early diagnosis of kidney damage long before conventional BUN and Creatinine become elevated. For additional information, please visit Heska’s website at: http://www.heska.com

Urine Protein Creatinine (Urine P:C) Ratio
A test distributed by IDEXX Laboratories allows veterinarians who have an IDEXX VetTest Chemistry Analyzer to measure Proteinurea and Creatinine from urine samples and use the results to calculate the ratio of protein to creatinine. The manufacturer says that the Urine P:C ratio can be used to diagnose CRF much earlier than the currently used testing methods and that the ratio of protein to creatinine is indicative of the seriousness of the disease which would permit the veterinarian to make a more accurate prognosis. For additional information, please visit IDEXX's website.

Studies

Posted July 14, 2010
Renal Disease Studies at Colorado State University

  • A study looking at whether fatty acids in the feline diet are related to antioxidant and anti-imflammatory effects that could protect a cat's kidneys
  • A study of the potential for using Mirtazipine as an appetite stimulant
  • Erythropoetin for anemic cats in a study at CSU
  • Free private cremation services for cats who have died from Chronic Renal Failure in exchange for post-mortem autopsy kidney samples

CVMBS Doctoral Student Awarded Fellowship to Study Kidney Disease

 

Posted June 15, 2009
Renal Disease Study Needs Patients for Enrollment

The Morris Animal Foundation has funded a new study at Colorado State University. Researchers at Colorado State University will be investigating whether an association between a common feline vaccine and renal disease exists. They are seeking blood samples from patients with and without renal disease that have a minimum of 5 years of vaccination history on record. The success of this study is completely dependent upon the willingness and interest of owners to enroll their cats in the study. Owners will receive a free blood biochemistry test and will contribute to our understanding of the causes of renal disease. More information about the study and how to enroll is available here.

A more detailed description of the study and official links to study documents can be found at the Center for Companion Animal Studies at Colorado State University's website.

Please note that the study will end this fall and sample submissions must be received by September 30, 2009 to receive a free biochemistry analysis.

Please contact Chelsea Sonius if you have any questions regarding the study or sample submission procedures.

Posted January 5, 2008
Azodyl

The Veterinary Information Network (VIN) is conducting a trial of Azodyl in Renal Failure Trial (ART).

ART is the first placebo-controlled clinical trial examining the efficacy of Azodyl ® in reducing azotemia and uremia in cats with chronic renal failure. This trial is being conducted by Dr. Mark Rishniw and Dr. Paul Pion at the Veterinary Information Network and has been largely funded by the VIN Foundation.

If you have a cat with CRF that might be eligible for the study, please discuss enrollment with your veterinarian and provide him/her with the link to the ART clinical trial page.

As of May, 2009 no data has been published as the study is not complete yet. If you are interested, it's not too late to enroll your cat in the study.

Posted January 9, 2008
Oxidative Stress and Antioxidant Therapy in Cats with Renal Failure

The Winn Feline Foundation recently announced the award of a new grant in 2007 - Oxidative Stress and Antioxidant Therapy in Cats with Renal Failure, Craig B. Webb, PhD, DVM; Colorado State University.  It is funded in partnership with the George Sydney and Phyllis Redman Miller Trust.  Click here for details about the study and also how to become a sponsor.

Stem Cell Study
We are pleased to see that research has been proposed and funded to study whether stem cells can be used to repair some of the damage caused by feline CRF. While this is a small scale study and it is unlikely, by itself, to result in a new therapeutic regimen, it is an important step forward.

Winn Foundation 2007 Grants Press Release - Scroll to last paragraph - Mesenchymal stem cell transfer for treatment of chronic renal disease in cats, Steven Dow, DVM, PhD; Colorado State University.

Fenoldopam
A study is currently underway at Auburn University on Fenoldopam. Fenoldopam is a drug originally developed to treat hypertension. It is being studied to determine its ability to increase both kidney function and urinary output in cats suffering from acute oliguric (low urinary output) renal failure.

Renal Effects and Characteristics of a Newly Identified Dopamine-1 Receptor in the Cat Kidney, Principal Investigator, James S. Wohl, DVM, Auburn University - Click on "feline", then "Kidney Diseases", then "D03FE-008".

FVRCP Vaccine

While research continues, it is extremely interesting that there may be a correlation between the FVRCP vaccine and chronic renal failure in cats.

Parenteral Administration of FVRCP Vaccines Induces Antibodies against Feline Renal Tissues, American College of Veterinary Internal Medicine

Vaccine Studies Raise Questions on Links to Kidney Disease in Cats, Colorado State University, College of Veterinary Medicine & Biomedical Sciences

March 4, 2008
The Winn Feline Foundation
recently announced the award of two new grants in 2008 related to feline chronic kidney disease:

Mirtazapine
Mirtazapine as an Appetite Stimulant and Anti-nausea Therapy for Cats with Chronic Kidney Disease, Katharine F. Lunn, PhD, MRCVS, DACVIM, Colorado State University. Mirtazapine is a human antidepressant but because some of its side effects include appetite stimulation and supperssion of nausea and vomiting, it may be beneficial to cats in chronic renal failure. This study will provide information on how the drug is metabolized and its efficacy in the treatment of cats in CRF.

L-Arginine
Safety and Bioavailability of Oral L-Arginine Supplementation in Cats with Naturally Occurring Chronic Renal Failure, Macon Miles, DVM; Animal Emergency Referral Center; Torrance, CA This study has been approved pending further funding. For information on how to donate to this study, please contact the Winn Feline Foundation.

September 6, 2008
Molecular characterization of Juvenile Renal Dysplasia in cats
Juvenile renal dysplasia (JRD) is the result of abnormal development of the kidney. Doctor Mary Whiteley is conducting a study to determine if JRD in cats is hereditary as it is in dogs. She is seeking participants for the study.

Potential participants would include any cat less than 3 years old of any breed that has received any of these diagnoses:

  • JRD (abnormal kidney development)
  • Renal cortical hypoplasia (incomplete development of the renal cortex)
  • Renal hypoplasia (again where the kidney does not develop completely)
  • Renal agenesis (an individual born with a missing kidney)
  • Ectopic ureters along with abnormal kidney development.

To participate in the study:

  • You will be asked to submit cheek swabs as DNA samples.
  • You will also be asked to provide any relevant medical information that you have on your cat, as well as any pedigree information that you may have.
  • You will be asked to sign a release for transferring the ownership of your cat’s DNA to DOGenes Inc.
  • There is no cost for participation.
  • Anyone wishing to participate in these studies should contact Doctor Whiteley directly at info@dogenes.com, or you can sign up for participation online at: https://www.dogenes.com/studylogin.html

Molecular characterization of calcium oxalate stone formation in cats

Doctor Whiteley has expanded her studies of renal diseases to include the molecular basis of calcium oxalate stone formation.

It is believed that there is a hereditary predisposition to calcium oxalate stone formation. In cats, certain breeds seem to be at a greater risk to developing calcium oxalate stones. There is a supposed breed disposition for calcium oxalate stones in dogs as well. Studies of both dogs and cats will be done in parallel.

For this study, Doctor Whiteley is seeking DNA from any cat of any age and breed that has developed calcium oxalate bladder stones.

To participate in the study:

  • You will be asked to submit cheek swabs as DNA samples.
  • You will also be asked to provide any relevant medical information that you have on your cat, as well as any pedigree information that you may have.
  • You will be asked to sign a release for transferring the ownership of your cat’s DNA to DOGenes Inc.
  • There is no cost for participation.
  • Anyone wishing to participate in these studies should contact Doctor Whiteley directly at info@dogenes.com, or you can sign up for participation online at: https://www.dogenes.com/studylogin.html

Please see our CRF Research section of the Links Page for links to Web sites containing news on clinical studies, new medications, etc. We would appreciate it if you would contact us at: if you have any new information on research or clinical trials being done.

Note: In order to reduce the overwhelming volume of spam we receive, we rendered the felinecrf_research address in the preceding paragraph as graphics rather than text so that automated address searchers cannot find it. You will have to type the address into an email message when corresponding with us. We sincerely apologize for the inconvenience.

Kidney illustration courtesy of:
Susie Bachman, Pawprints & Purrs, Inc
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