What is CRF

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					                                           All Cats HealthCare Clinic
                                               1034 N.W. 13th ST.
                                              Gainesville, FL 32601
                                             Patti Gordon, DVM
                                            Jocelyn Ramey, DVM
                                        Office phone: (352) 376-2287
                            This information provided by: www.felinecrf.com


                                                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. For additional information
about feline ARF, we recommend this website:
Acute Renal Failure

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


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