Introduction

In many ways, this page is not particularly important, because in most cases it does not matter how a cat developed CRF - the treatment is the same once it is present (although in the case of glomerulonephritis, there may be other things which can be tried). However, I am including the information because so many people seem to blame themselves for their cat's illness, when in truth CRF is rarely avoidable - as the What is CRF? page mentions, around 10% of cats over the age of ten will develop CRF, with as many as 30% of cats over the age of 15 having the disease.

The possible causes section is just that at this point, possible causes; there is no hard evidence that any of these possibilities truly do cause CRF, although the anecdotal evidence is stronger for some (dental problems, hypertension) than for others.

The following sites have overviews of the causes of CRF:

Selected diseases of the feline kidney (2001) is a paper presented by Dr Stephen DiBartola to the World Small Animal Veterinary Association World Congress.

Renal diseases in cats (2002) is a presentation by JP Pagès to the 27th World Small Animal Veterinary Association Congress.

Washington State University College of Veterinaey Medicine has information on potential causes of CRF (scroll down a bit).

The Pet Center has some helpful information.

Hereditary/Congenital Abnormalities

Polycystic Kidney Disease (PKD)

Polycystic Kidney Disease is a condition in which cysts form on the kidneys. There is detailed information about PKD on the Related Diseases page.

Renal Dysplasia and Renal Hypoplasia

In these conditions, the kidneys either do  not develop normally (renal dysplasia) or they do not develop completely (renal hypoplasia). In some cases of renal hypoplasia, known as renal aplasia, the cat has only one kidney. Cats with only one kidney tend to be male, and for some reason it is usually the right kidney which is missing. Cats who develop CRF at an early age often suffer from renal dysplasia or renal hypoplasia. The What Do All Those Test Results Mean? page has information on renomegaly (enlarged kidneys).

Merck Veterinary Manual has some information on these conditions.

Infections

Pyelonephritis

Pyelonephritis is a bacterial infection of the kidneys. The cat may also have a lower urinary tract infection -  in some cases, untreated lower urinary tract infections rise into the kidneys - but not always. Cats with PKD are particularly prone to pyelonephritis, since the bacteria can burrow into the cysts. Our PKD cat, Harpsie, gets regular bouts of pyelonephritis.

A urine culture and sensitivity will be taken, though it is relatively common for nothing to grow in a culture if the cat has a kidney infection rather than a lower urinary tract infection. Ultrasound may be helpful in diagnosing the existence of pyelonephritis, though this can be of limited value in cats with PKD, whose kidneys already look abnormal.

In order to be sure that the bacteria are completely eradicated and the infection completely cured, as recommended by Washington State University college of Veterinary Medicine, cats with kidney infections require a prolonged course of antibiotics, for four to six weeks or longer. This is because blood flow to the site of most kidney infections is poor, so it can take a while for the antibiotics to reach and kill the bacteria.  If your cat has a kidney infection, the bloodwork may improve once the infection is under control.

Washington State University College of Veterinary Medicine discusses pyelonephritis.

Urinary tract infection (UTI): how to diagnose correctly and treat (2003) is a presentation by Dr C Brovida to the 28th World Congress of the World Small Animal Veterinary Association, and includes information on pyelonephritis.

FIP (Feline Infectious Peritonitis)

Cats with the non-effusive form  of FIP sometimes have enlarged kidneys and kidney problems. However, very few cats on the Feline CRF Information list have FIP.

Dr Diane Addie is a lecturer in veterinary virology, and is an expert on FIP. Her site is available in a number of different languages.

Newman Veterinary has information on FIP.

Cornell University College of Veterinary Medicine has a good overview.

Inflammation

Glomerulonephritis

The glomeruli are very fine blood vessels in the kidneys that act as filters of waste products to produce urine. If they are damaged, blood proteins, which would normally be recycled into the bloodstream, may leak out into the urine (proteinuria). In severe cases, the resulting low levels of protein in the blood may cause weight loss and a build-up of fluids under the skin (sub-cutaneous oedema). 

Glomerular disease is an immune-mediated disease, and is not as common as interstitial disease. It is actually relatively rare in cats, and is usually secondary to some other condition such as an infection, inflammatory disease or diabetes. Glomerulonephritis is often managed differently to CRF - using medications to suppress the immune system may help, whilst ACE inhibitors may also be of use for this condition because they appear to reduce proteinuria.

In the worst case, glomerulonephritis may result in something called nephrotic syndrome. Nephrotic syndrome is not a disease in itself, but rather a collection of symptoms that may be seen as a result of the glomerular problems. The primary symptoms of nephrotic syndrome include proteinuria, oedema and/or ascites, low albumin levels and high cholesterol levels. You may also see diarrhoea, reduced urine output, anaemia and occasionally saddle thrombus (a blood clot in the leg). However, since glomerulonephritis itself is relatively rare in cats, so is nephrotic syndrome.

Pet Place has a helpful overview of glomerulonephritis.

Dr Katherine James has information about both glomerulonephritis and nephrotic syndrome.

Mar Vista Vet has very helpful information, including information on how to treat glomerulonephritis.

Washington State University College of Veterinary Medicine has information about glomerulonephritis.

Protein losing nephropathy: an overview (2004) Wallace MS discusses glomerulonephritis and amyloidosis.

Washington State University College of Veterinary Medicine has information about nephrotic syndrome.

Merck Veterinary Manual has interesting, albeit rather technical, information.

E Cure Me is a human site with information about nephrotic syndrome.
 

Chronic Interstitial Nephritis

Essentially, this is what we commonly think of as CRF. It may be caused by any of the other problems described on this page, though it may also be considered to be "old age" kidney disease. As humans age, they are likely to develop cancer; whereas cats are more likely to develop kidney disease.

Selected diseases of the feline kidney (2001) is a paper presented by Dr Stephen DiBartola to the World Small Animal Veterinary Association World Congress, which includes this condition.

Merck Veterinary Manual has some information on interstitial nephritis and CRF.

Renal Calculi (Stones) and Obstructions

Renal calculi (kidney stones) may cause kidney problems. The stones may calcify, and cause damage that way, or they may lodge in the ureter, thus allowing waste products that would normally be excreted by the bladder to build up in the kidneys - this is called obstructive nephropathy. If a cat's kidney bloodwork suddenly becomes extremely high, a kidney stone blocking the ureter may be the cause. Most kidney stones are calcium oxalate stones.

Urinary tract blockages (see Links and Resources), which tend to be caused by the opposite problem, struvite crystals (see below), may cause acute renal failure if not treated promptly, and in some cases there may be permanent chronic damage. 

For some cats, calcium oxalate stones may be caused by a Vitamin B6 deficiency, in which case a Vitamin B supplement may help (be guided by your vet as to an appropriate brand).

As it happens, foods formulated for CRF, such as Hill's k/d, are also suitable for cats with calcium oxalate stones, whether or not they have CRF.

Mar Vista Vet gives a good overview of calcium oxalate stones.

Ureteral dilemma: non-surgical management of ureteroliths (2007) Adams LG Hill's Symposium on Lower Urinary Tract Disease 2007 pp14-21 discusses possible treatment options. Scroll down to page 14.

Management and outcome of cats with ureteral calculi: 153 cases (1984 - 2002) (2005) Kyles AE, Hardie EM, Wooden BG, Adin CA, Stone EA, Gregory CR, Mathews KG, Cowgill LD, Vaden S, Nyland TG, Ling GV. Journal of the American Veterinary Medical Association 226(6) pp937-44 discusses a large number of cases over a period of eighteen years, and states that even after successful treatment, many cats will have impaired renal function.

Oxalate degradation by intestinal lactic acid bacteria in dogs and cats (2004) Weese JS, Weese HE, Yuricek L, Rousseau J Veterinary Microbiology 101(3) pp161-6 mentions that the use of prebiotics, including fructooligosaccharide products (FOS), a type of fermentable fibre, may help reduce the formation of calcium oxalate stones.

Harpsie's Website has some information about stones and blockages.

Cancer - Renal Lymphoma (Lymphosarcoma)

Lymphoma (lymphosarcoma) is the most common type of renal cancer in cats. White blood cells called lymphocytes become cancerous and produce tumours. Around 50% of cats with lymphoma also have feline leukaemia.

Lymphoma may be found in several parts of the body; if it occurs in the kidneys, it is called renal lymphoma. As renal lymphoma progresses, it may cause renal failure. There are a number of possible treatment options, usually revolving around chemotherapy.

Renal diseases in cats (2002) is a presentation by JP Pagès to the 27th World Small Animal Veterinary Association Congress. Section 2.5 discusses renal cancer.

The Feline Cancer Resources Website has information and many links.

There are more links about feline cancer, including lymphoma, on the Links and Resources page.

Toxins

Lilies and Antifreeze

Common nephrotoxics include lilies and antifreeze, which cats may lick or eat accidentally (the taste of antifreeze is unfortunately very attractive to cats). In most cases these cause Acute Renal Failure (see Links and Resources) but in some cases, if the cat recovers, there may be residual kidney damage resulting in CRF.

Lilies

Cats and Kittens Magazine has information from the ASPCA on the dangers of lilies - they cause acute renal failure in cats.

Purdue University School of Veterinary Medicine has information on lily toxicity for cats.

Cats Protection also has information on lily toxicity.

Antifreeze

US Food & Drug Administration - antidote for antifreeze poisoning Anti-freeze is a common cause of acute renal failure. Cats may sometimes appear to recover, but will then become ill once again; it is critical to seek veterinary treatment as early as possible, even if the cat appears to be recovering; early treatment greatly influences the cat's chances of survival.

Washington State University College of Veterinary Medicine - detailed information on antifreeze poisoning.

Pet Place - three pages of detailed information on antifreeze poisoning.

Metacam (Meloxicam)

Metacam (meloxicam) is a non-steroidal anti-inflammatory drug (NSAID) available in both injectible and liquid (oral) form. It is approved for use in dogs in both forms, but since cats tend to metabolise NSAIDs very poorly, in the USA meloxicam is only approved for use in cats in its injectible form. This is because it is intended to be a one-off treatment as a painkilling injection following surgery.

This was also the case in Europe, but in June 2007, the oral form of Metacam was licensed for cats for longer term pain management e.g. for use in cats with arthritis. The new feline version of Metacam is a 0.5mg/ml oral suspension compared to the canine version which is a 1.5mg/ml suspension.

In the USA, meloxicam also appears to be being used more and more frequently off-label for cats in its liquid (oral) form on an ongoing basis, but because there is no feline version available, vets are using the canine version at reduced doses.

Unfortunately meloxicam is nephrotoxic, i.e. toxic to the kidneys. In fact, it can cause permanent damage to the kidneys (papillary necrosis), with the result that a number of cats seem to have developed acute or chronic renal failure after taking meloxicam. I am therefore mystified as to why the drug has been approved for ongoing use in cats in Europe.

Although meloxicam is very effective at controlling pain, I would not recommend its use in a cat who already has CRF, and I would be very cautious about using it in cats generally. We did use it for Harpsie's arthritis without any problems, but we gave a tiny dose, less frequently than recommended, and we checked his kidney values a month later.  

I would recommend only using Metacam in exceptional circumstances. If you do use it, and your cat develops renal failure, please see below for information on how best to treat it.

Metacam may interact with ACE inhibitors such as benazepril (Fortekor or Lotensin) or enalapril (Enacard) so do not give both medications to your cat  without checking with your vet first. 

Dealing with Adverse Reactions to Metacam in the USA

If you believe your cat has developed renal failure as a result of using Metacam, you should report this to the manufacturers. The number to call is 1-866-METACAM (638-2226). You will probably find yourself speaking to a Dr Carey, who should work with your vet to devise a treatment plan.

Most cats who suffer renal failure as a result of using Metacam are suffering from acute renal failure (ARF) and their bloodwork may be extremely high, with creatinine often in the high teens. Do not give up hope! Acute renal failure is difficult to treat, but not impossible: an aggressive treatment plan should see those numbers dramatically reduce in most cases, so don't opt for euthanasia immediately.

A treatment programme which includes 4-5 days of IV fluid therapy (hospitalisation), followed by 4-6 weeks of sub-Q fluids at home, is often recommended by the manufacturers, but talk to them and see what they suggest for your cat. I would also suggest that you ask the manufacturers to pay your veterinary costs - I know they have done this for some people, although they have not necessarily paid the full costs.

You should also make a report to the Food & Drug Administration. Apparently the manufacturers are not obliged to report any cases of renal failure to the FDA because renal failure is already listed in the package insert as a possible side effect (see the second link below). But I believe it is very important for the FDA to be fully aware of the scale of the problem. FDA Consumer Complaints Co-ordinator has details of the relevant contacts for each state.

Metacam Links

Metacam Reference Page is a summary by the manufacturer of the approval for the use of Metacam in cats, which states that it is approved for one-off injectible use only.

The Metacam Professional Insert, approved by the US Food and Drug Administration, states (page 2): "renal failure has been reported as an outcome of repeated oral dosing of cats".

Freedom of Information Summary (2004) from the US Food and Drug Administration mentions on page 23 that, following the use of Metacam for post-operative pain, 8.3% of the cats in the study had elevated BUN levels, and 12.5% had anaemia. In comparison, there were no cases of elevated BUN levels in cats in the study given another post-operative painkiller, although 6.1% of them did have anaemia (one possible cause of anaemia is inflammation, which may partly explain this finding). The paper concludes: "Meloxicam, when initially dosed as a subcutaneous injection followed by oral dosing for nine days at > 0.3 mg/kg was associated with severe adverse effects, including death."

The US Food and Drug Administration reprimanded the manufacturers of Metacam in 2003 for misleading claims for the product and omission of important safety claims.

The European Medicines Agency states (P36) "do not use in animals suffering from gastrointestinal disorders such as irritation and haemorrhage, impaired hepatic, cardiac or renal function." It also says (P103) that the use of Metacam should be avoided in dehydrated animals "as there is a potential risk of renal toxicity", and warns that the oral form of Metacam should not be used following use of the injectible form.

Pet Place has some information on Metacam, and advises against using it in cats until further tests have been completed. Even if the injectible form of Metacam is used post-operatively, this has only been tested on cats given one particular type of anaesthesia.

Mar Vista Vet also has some information about Metacam and recommends avoiding its use in cats with kidney, liver or heart disease, as well as in cats who are dehydrated or who have stomach ulcers.

Provet has some warnings about the use of Metacam.

Metacam Risks in Cats is an article by Persian and Himalayan Cat Rescue.

Arthritis in Cats and Dogs Pet Forum contains some postings from members who experienced problems when using Metacam on their cats (although some, like us, had good results).

Metacam UK this is the manufacturer's British website about the use of Metacam in dogs. It mentions the recent approval of the drug for ongoing use in cats, but has very little information about this.

Metacam USA this is the manufacturer's American website about the use of Metacam in dogs.

Auto-Immune Diseases

Amyloidosis

Amyloid is a type of protein found in the body. In amyloidosis, amyloid is deposited in organs and tissues where it does not belong, and it adversely affects them. In cats, the deposits are often found in the kidneys, and they eventually lead to CRF. Amyloidosis is not particularly common, but it may be found in Abyssinian cats in particular, and sometimes in Siamese and Oriental cats.

Washington State University College of Veterinary Medicine has some information about amyloidosis.

Protein losing nephropathy: an overview (2004) Wallace MS discusses glomerulonephritis and amyloidosis.

Perinephric Pseudocysts

Perinephric pseudocysts are large fluid-filled sacs that form around one or both of a cat's kidneys. They appear to be more common in male cats, and the cat may appear healthy apart from having an abdomen that is increasing in size but not usually tender to the touch. Upon examination, which is usually performed via ultrasound,  the kidneys are usually enlarged.

The cysts may be treated by draining the fluid, but this is often only a temporary measure. Removing the wall of the cyst may be more effective, but in more severe cases it may be necessary to remove a kidney. However, this is a last resort because it may lead to CRF, since many cats with these cysts tend to have compromised kidneys  (they are often already in early stage CRF) and/or urinary tract infections. However, the first link below does state that the prognosis is usually good if accompanying CRF is not severe and no other diseases are present.

Perinephric pseudocysts in the cat: a retrospective study and review of the literature (1999) Ochoa VB, DiBartola SP, Chew DJ, Westropp J, Carothers M, Biller D Journal of Veterinary Internal Medicine 13(1) pp47-55 reports on thirteen such cases.

Clinical exposures: a perinephric pseudocyst in a cat (2005) Morrow BL Veterinary Medicine reports on a cat with this problem and provides a good overview of these cysts and treatment options.

Berkshire Vet tells how cysts were successfully removed from a young cat called Daisee.

Suspected Causes (Not Proven)

These are just that - areas where people have their suspicions, but there is no real evidence that these are causes of CRF, although the evidence for some, such as dental problems, is stronger than for others. Further research is needed, and in some cases is ongoing.

Dental Problems

In humans, there is a correlation between dental disease and heart disease; but in cats it appears that dental disease is linked to kidney disease. Many cats appear to develop CRF shortly after having a dental, often without the precautions appropriate for older cats. On the other hand, cats who never receive dental care also seem to be at increased risk of kidney disease. This topic is covered in detail on the Related Diseases page.

Pfizer Animal Health mentions that dental problems may lead to kidney failure.

Hypertension

For many years it was thought that hypertension in cats was the result of another condition, such as CRF or hyperthyroidism. Whilst it is true that hypertension is more common in cats with these conditions, it is gradually becoming clear that primary hypertension does exist in cats, and may in fact contribute to the development of CRF. There is more information about hypertension in the Symptoms, What Do All Those Test Results Mean? and Treatments pages.

Feline hypertension: risks and management (2005) is a presentation by Dr Clarke Atkins to the  World Small Animal Veterinary Association Thirtieth World Congress, in which he states "adding to the confusion in understanding the pathogenesis of hypertensive renal disease, renal disease begets hypertension and hypertension begets renal disease"

A Vaccination Connection?

A study at Colorado State University, Parenteral administration of FVRCP vaccines induces antibodies against feline renal tissues (2002) Lappin MR, Jensen WA, Chandrashekar R & Kinney SD Presentatation to the American College of Veterinary Internal Medicine Forum, Dallas, indicates a tentative connection between feline vaccinations and renal failure. 

The connection arises because feline vaccines are grown on kidney cells known as Crandell Reese Feline Kidney (CRFK) cells. It has long been known that growing the vaccines in this way produces some unidentified antibodies in addition to those required for the vaccine, but it has only recently been discovered that the unidentified antibodies were to renal tissue. These additional antibodies occur in all modified live or killed vaccines, but do not occur with intranasal vaccines. In the UK, live vaccines are usually used.

In a further study, Investigation of the induction of antibodies against Crandell-Rees feline kidney cell lysates and feline renal cell lysates after parenteral administration of vaccines against feline viral rhinotracheitis, calicivirus, and panleukopenia in cats (2005) Lappin MR, Jensen WA, Jensen TD, Basaraba RJ, Brown CA, Radecki SV, Hawley JR American Journal of Veterinary Research 66(3) pp506-511 it was concluded that "hypersensitization with CRFK cell proteins did not result in renal disease in cats during the 56-week study".

A more recent study, Interstitial nephritis in cats inoculated with Crandell Rees feline kidney cell lysates (2006) Lappin MR, Basaraba RJ, Jensen WA Journal of Feline Medicine and Surgery 8(5) pp353-6, found that 50% of the cats in the study who were given normal vaccines developed interstitial nephritis (CRF) according to biopsies. However, these cats were vaccinated 12 times in 50 weeks, which is obviously far more often than is normal (the current US guidelines are for cats to be vaccinated only once every three years). One group of cats in the study were given intranasal vaccines, and they did not develop any signs of interstitial nephritis.

I have been in contact with Dr Lappin, who led the studies, and he tells me that he currently (2007) advises following the 2006 American Association of Feline Practitioners guidelines for vaccinating cats. He also recommends only giving vaccines that are appropriate for your cat's situation. 

Regardless of these findings, I would not recommend giving any vaccines to a cat who already has CRF: vaccines are intended for healthy cats and a CRF cat is not healthy. Once Thomas had been diagnosed, our vet felt it was not wise to give him his usual vaccinations, and we agreed with her. For healthy cats, intranasal vaccines appear to be safer. Please see the Treatments page for more information on the use of vaccines in cats, and discuss what is appropriate for your own cat with your vet.

Colorado State University has a report on the Lappin study.

Heska has information about intranasal vaccines.

Heska also has a presentation by Dr Lappin about the current vaccination debate (this is rather technical).

Potassium Depletion

One study, Chronic renal disease and potassium depletion in cats (1992) (no abstract provided) Dow SW & Fettman MJ Seminars in Veterinary Medicine and Surgery (Small Animal) 7 (3) pp198-201, suggested that all cats with CRF should be supplemented with potassium, even if they do not appear to have low potassium levels. Some people go further and believe that all older cats should be supplemented with potassium, whether they have CRF or not. 

Whilst it is true that potassium blood tests may not accurately reflect potassium levels at the cellular level, where the potassium is needed (see What Do All Those Test Results Mean? for more on this), this does not automatically mean that every cat would benefit from potassium supplementation. A more recent study, Muscle potassium content and potassium glouconate supplementation in normokalemic cats with naturally ocurring chronic renal failure (1997) Theisen SK, DiBartola SP, Radin MJ, Chew DJ, Buffington CA, Dow SW Journal of Veterinary Internal Medicine 11(4) pp212-217, found that CRF cats with normal potassium levels who were given potassium supplementation did no better than similar cats who received a placebo.

Feeding potassium-restricted acidified diets (see below) to cats with normal renal function reduces gastro-intestinal absorption of potassium and may therefore lead to potassium depletion. I therefore would not recommend feeding such diets to older cats; and these diets should not be fed to CRF cats anyway (see Food Composition and Nutritional Requirements).

I would be wary about giving potassium to any cat with a serum potassium level much over 4 - high potassium levels may develop quickly, particularly as the CRF progresses, and are potentially very dangerous (see What Do All Those Test Results Mean?). 

Dry Food Diet

It is thought that feeding an exclusively dry food diet may cause chronic dehydration, which in turn may cause CRF. This is not proven, but it is true that cats generally benefit from more water in their diet, particularly CRF cats, as do cats with FLUTD. The Food Composition and Nutritional Requirements page has more information on dry food versus wet.

Acidified Diets

Many commercial diets over the last ten years have been re-formulated to promote "urinary tract health", or words along those lines. Essentially, these diets are acidified, so as to reduce the risk of cats developing FLUTD - cats with FLUTD tend to have urine that is too alkaline, and are therefore at risk of developing struvite crystals, which develop in an alkaline environment. However, feeding these diets to cats who are not at risk of FLUTD may lead to urine that is too acidic. This may in turn result in the opposite problem to struvite crystals, i.e. calcium oxalate stones, which develop in an overly acidic environment. These stones, unlike struvite, cannot be dissolved by diet - they can only be removed by surgery. It is speculated that the existence of acidified diets may be a factor in the increase in renal calculi (kidney stones), which in turn are a risk factor for developing CRF.

Acidified diets may also contribute to low potassium levels.

Free Feeding

A 2002 study, Diet and lifestyle variables as risk factors for chronic renal failure in pet cats (2002) Hughes KL, Slater MR, Geller S, Burkholder WJ, Fitzgerald C Preventive Veterinary Medicine 55(1) pp1-15, compared cats in three groups: free feeding with fibre; free feeding with Factor-2 (a composite variable composed of fiber, magnesium, protein, sodium and ash); and fibre alone. The researchers concluded that free feeding was associated with increased odds of developing CRF. However, they did not simply free feed the cats; they also gave them additives. It is therefore not known whether free feeding alone would give similar results.

I myself have always free fed, and will continue to do so. In the wild, cats naturally feed multiple times a day. See Food Composition and Nutritional Requirements for more information on this topic.

New Flooring

Some people on the Feline CRF Information list believe that new carpets and floors contain potential toxins for cats - several people have noted that their cats developed CRF shortly after new flooring was laid. Carpets and other floor coverings may contain various volatile organic compounds, particularly in the backing. The Carpet and Rug Institute in the USA recommends ventilating the area where new carpet is installed for 48 - 72 hours. Cats appear to be particularly sensitive to smells; essential oils, for example, are toxic to cats, who lack the metabolic pathways to process them. I therefore would recommend keeping cats away from new carpets and floors for several days after installation, if possible.