Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

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Calcium Oxalate Urolithiasis

Related terms: crystalluria; Stones, bladder stones

VeNom term:  rolithiasis/crystalluria - calcium oxalate (VeNom code: 2062)

Related conditions: hypercalciuria

Outline:

Calcium oxalate stones are formed in the urinary tract when calcium and oxalate ions combine. Persian cats have a greater risk of forming stones of calcium oxalate than some other cat breeds. Diet and water intake, and the volume and frequency of urination can influence stone formation. Stones can irritate, inflame and/or damage the bladder or urethral walls, and therefore cause pain, and cats with stones are more prone to urinary tract infections and urinary tract obstruction.

The genetic mechanisms underlying the greater risk of stone formation in Persians are unknown but stone formation is more common in males than females.


Summary of Information

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1. Brief description

Urolithiasis is a condition in which mineral crystals in urine combine to form stones (also called uroliths, calculi or ‘stones’). Stones are classified based on the type of minerals that they are composed of, and commonly are formed from any of 10 different minerals, either combined in various combinations or individually; calcium oxalate stones are formed when calcium and oxalate ions combine. These stones can develop or reside anywhere in the urinary tract - in the kidney, ureter, bladder or urethra – and their presence causes irritation and secondary infection. Most stones end up in the bladder or in the urethra, where they may cause obstruction.

The underlying causes of calcium oxalate urolith formation in cats are unknown and it is thought to be a complex process. Such stones are more likely to develop when there are high concentrations of calcium and oxalic acid in the urine and when crystals of these chemicals travel slowly along the urinary tract. Urinary tract infection, diet and water intake, and the volume and frequency of urination can influence both these factors.

Stones may irritate, inflame and damage the bladder or urethral walls. Large or multiple stones may cause obstruction in the bladder or urethra and in severe cases, this may cause bladder rupture. Obstructive urolithiasis is a medical emergency and rapid veterinary treatment is required to prevent death.

2. Intensity of welfare impact   

Small stones may cause minimal adverse effects and can be passed from the urinary tract during urination, without the need for intervention. However, even small stones can irritate, inflame and damage the bladder or urethral walls and thereby cause pain and the appearance of blood in the urine. Urinary tract infections are commonly associated with stones and are likely to cause persistent pain.

Multiple or large stones can cause partial or complete obstruction to the urethra, the duct by which urine is passed out of the body, and lead to urine retention. Animals with urethral obstruction may attempt to urinate frequently but pass little urine and may experience extreme pain and distress when urinating, which increases with the volume of urine of retained. In cases of severe obstruction, if appropriate treatment is not given promptly, the overfilled bladder may rupture, leading to infection and serious complications, which could result in death within hours. Treatment often requires major surgery, which has its own welfare implications.

3. Duration of welfare impact

Older cats are more commonly affected by calcium oxalate stones, and they commonly reoccur in affected animals. Dietary and environmental management may reduce the risk of calcium oxalate urolith development.

4. Number of animals affected

Calcium oxalate stones are the most common type of urinary stone to occur in cats. Persian cats have a higher risk of developing calcium oxalate stones than other breeds.

Male cats and neutered males are more at risk of developing obstruction with calcium oxalate stones than female cats.

5. Diagnosis

Stones can be diagnosed with an x-ray or ultrasound scan of the urinary tract. Quantitative analysis of stones is recommended, eg via optical crystallography or infrared spectroscopy, to identify which minerals they contain.

6. Genetics

The genetic mechanisms of urolith development in Persians are not known, but it is suspected that some factors relating to calcium oxalate urolithiasis may be inherited in this breed.

7. How do you know if an animal is a carrier or likely to become affected?

Currently, it is not known which individual animals are more likely to become affected. We do know that Persian cats – especially males – are more at risk of developing obstruction with calcium oxalate stones.

8. Methods and prospects for elimination of the problem

Since the genetic mechanisms for the development of calcium oxalate stones in Persians are unknown, the methods for elimination or reduction of the problem are limited.

Environmental factors, such as diet and exercise play an important role in reducing the risk of urolith development.


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1.  Clinical and pathological effects

Urolithiasis is a condition in which mineral crystals in urine combine to form stones (also called uroliths or calculi). Stones can be composed of individual or combinations of approximately 10 different minerals, and stones are classified based on the type of minerals that form them. Calcium oxalate is a calcium salt of oxalic acid and forms when calcium and oxalate ions combine; they are one of the most common types of stones in cats; 40% of all feline stones are calcium oxalate (Buffington & Chew 2009). Although there are different combinations of calcium oxalate salts, calcium oxalate stones are most commonly the monohydrate form (crystal name: whewellite) rather than the dihydrate form (weddellite) in cats (Dijcker et al 2011). Stones can develop or reside anywhere in the urinary tract - in the kidney, ureter, bladder or urethra – and commonly cause irritation and secondary infection. Most stones end up in the bladder, kidney or the urethra, where they may cause obstruction (Cannon et al 2007).

The underlying causes of calcium oxalate stone formation in cats are unknown and it is thought to be a complex process, involving several factors. High concentrations of calcium and oxalic acid in the urine and a slow passage of crystals of these minerals along the urinary tract contribute to stone formation. Normally, urine is of an acidity that means calcium and oxalic acid remain dissolved within it, but if the urine becomes less acidic or if there are high levels of these chemicals in the urine a threshold is reached, and crystals begin to spontaneously develop, clump together and grow (Bartges et al 1999). Stone formation can be accelerated by other factors such as urinary tract infection, a high calcium diet, low water intake, and a decreased volume and frequency of urination. Excessive concentrations of calcium in the blood (hypercalcemia) or urine (hypercalciuria) can result from excessive dietary intake of calcium, impaired retention of calcium by the kidneys, and/or excessive calcium released from bones (McClain et al 2014).

Stones may irritate, inflame and damage the bladder or urethral walls. Cats may have difficulties and pain when urinating and there may be blood in the urine (hematuria).

Urolithiasis is the second most common cause of lower urinary tract disease (after idiopathic cystitis; (Bartges et al 2004, McClain et al 2014). Affected cats are prone to urinary tract infections, which may cause pain (McClain et al 2014). It is not clear whether these infections are a primary cause of the urolithiasis or a secondary factor resulting from the urinary stones. Cats with urinary tract infections may have blood in the urine and show abnormal urination patterns, with voiding of small frequencies, abnormal postures (standing versus squatting) and voiding in different locations due to an association of pain with the location of previous urination (McClain et al 2014). Multiple or large stones may cause obstruction in the urinary tract and lead to urine retention. If the stones completely block the urethra (the tube from the bladder to outside), affected cats will show signs of increasing distress and frequently trying but failing to pass urine. These cats may vomit, be anorexic (not want to eat) and have a tender abdomen. This is a medical emergency and if an animal is left for long in this state, they can rapidly become very sick.  Within a few hours, the overfilled bladder may rupture, leading to infection and inflammation of the abdominal lining (peritonitis) and gut absorption of toxins and potassium from the urine. This can cause excessive levels of acid in the blood (metabolic acidosis) and extremely high levels of potassium in the blood (hyperkalemia), leading to cardiac arrest and death.

Cats with the condition will often eliminate in inappropriate places (eg in the house); possibly because they associate pain to the location of previous elimination spots (eg a litter tray or outside). This change in toileting behaviour may persist even when the infection has been cleared, and stress caused by punishment by owners may exacerbate the problem.

A study found several environmental factors associated with an increased risk of calcium oxalate urolithiasis in cats, including feeding urine-acidifying diets, feeding a single brand of cat food without providing additional foods and/or maintaining cats in an indoor-only environment (Kirk et al 1995).

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2. Intensity of welfare impact

Small stones may cause minimal adverse effect and may pass uneventfully from the urinary tract, without the need for intervention, during normal urination. However, even small stones can still irritate, inflame and damage the bladder or urethral walls, and therefore affected cats may have difficulties when urinating with pain and discomfort.

Urinary tract infections are commonly associated with stones (Bartges et al 2004) and are likely to be painful. Blockages to urine outflow in the urethra (the tube from the bladder to outside) can cause moderate to extreme pain as the animal repeatedly tries to pass urine. The pain increases in intensity as the bladder becomes fuller. Also, due to the associated secondary kidney failure, affected individuals rapidly feel very ill, do not want to eat and start to vomit. Animals can die from a blocked urinary system within 24-48 hours without appropriate treatment. In cases of severe obstruction, the overfilled bladder may rupture, leading to infection, inflammation of the abdominal lining (peritonitis) and gut absorption of toxins and potassium from the urine. This can cause excessive levels of acid in the blood (metabolic acidosis) and extremely high levels of potassium in the blood (hyperkalemia), leading to cardiac arrest and death.

Appropriate treatment of stones depends on the location of the urolith and its chemical composition, as well as on patient-specific factors, but it may include dietary and medical management (eg managing urinary tract infections) or stone removal. Smaller stones can be removed non-surgical by urohydropropulsion, where the stones are flushed out using a special urinary catheter technique whilst the cat is anaesthetised (Bartges et al 1999). Larger stones are removed via surgery. Both procedures may cause distress, discomfort and pain, and there may be complications such as kidney damage. Surgical intervention is necessary for the emergency treatment of urethral blockages.

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3. Duration of welfare impact

Calcium oxalate stones more commonly affect older cats, with an average (mean) age of 7 to 7.5 years (Lekcharoensuk et al 2000, Picavet et al 2007).

Reoccurrence of stones, in cats in general, is common and, in one study, occurred in 8% of affected cats within a 1-year period at a single centre in Minnesota (Albasan et al 2009). The pain and discomfort associated with inflammation of the urinary tract can last weeks and is unlikely to resolve without treatment. Dietary management, for example, reduced calcium and sodium intake, may reduce the risk of calcium oxalate urolith development (Dijcker et al 2011).

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4. Number of animals affected

The number of calcium oxalate urolithiasis in cats submitted to Hill’s Pet Nutrition Benelux (Belgium, The Netherlands and Luxemburg) increased significantly over a 10-year period from below 50 in 1994 to just below 300 stones in 2004 (Picavet et al 2007).

Persian cats have a higher risk of developing calcium oxalate stones than other breeds (Kirk et al 1995, Thumchai et al 1996, Lekcharoensuk et al 2000). In the Unites States, 722 Persians of 4698 had calcium oxalate stones, which is an odds ratio of 3.53 (95% confidence interval: 3.22-3.86; (Lekcharoensuk et al 2000).

Male cats are 1.5 times more likely to develop calcium oxalate stones than females, and neutered cats (male and female) are 7 times more likely to develop stones compared to sexually intact cats. (Lekcharoensuk et al 2000). The explanation for this difference in cats is unknown but it is thought to be due to differences in the quality and quantity of urinary crystal aggregation and/or the protective effects of female hormones in decreasing urine calcium concentration. It is also possible that stones, of even a small size, are more noticeable in the narrower urethra in males, leading to greater diagnosis.

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5. Diagnosis

Stones can be diagnosed using radiography or ultrasonography of the bladder. Where there are many stones, or when stones are large, veterinarians may be able to physically feel the stones in the bladder.

It is important to also identify the composition and structure of the stones at diagnosis, for effective treatment. Quantitative analysis of stones is recommended, eg via optical crystallography or infrared spectroscopy.

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6. Genetics

A predisposition to form calcium oxalate stones has been shown to be passed down to family members in humans (Goodman et al 1995) and rats (Bushinsky et al 1995), but to date, has not been reported in cats. Persians have a greater risk of developing calcium oxalate stones (Kirk et al 1995, Thumchai et al 1996, Lekcharoensuk et al 2000) and these studies suggest that some factors relating to calcium oxalate urolithiasis may be of an inherited nature. However, there may be important environmental factors relating to the way Persians are kept, which may cause the predisposition.

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7. How do you know if an animal is a carrier or likely to become affected?

It is currently not known which individual animals are more likely to become affected. We do know that the Persian breed is more at risk of developing calcium oxalate stones. Males, especially neutered males, of the Persian breed are more prone to calcium oxalate stones compared to females and intact males.

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8. Methods and prospects for elimination of the problem

Since the genetic mechanisms for the development of calcium oxalate stones in Persians are unknown, the methods for genetic reductions of the problem are limited (Lyons 2010). Further work is necessary to determine the genetic interactions in the pathophysiology of calcium oxalate uroliths in Persian cats. Control of diet and environment, for example increased water intake, feeding alkaline or varied diets and access to outdoors, may help reduce the risk of calcium oxalate urolithiasis, even in breeds predisposed to the condition.

The best advice that can be offered to prospective breeders is to avoid breeding between severely affected cats or cats with severely affected relatives including grandparents, siblings, previous offspring and siblings of parents.

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9. Acknowledgements

UFAW thanks Dr Emma Buckland (BSc PhD), Dr David Brodbelt (MA VetMB PhD DVA DipECVAA MRCVS) and Dr Dan O’Neill (MVB BSc MSc PhD MRCVS) for their work in compiling this section.

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10. References

 Albasan H, Osborne CA, Lulich JP, Lekcharoensuk C, Koehler LA, Ulrich LK and Swanson LL (2009) Rate and frequency of recurrence of uroliths after an initial ammonium urate, calcium oxalate, or struvite urolith in cats. Journal of the American Veterinary Medical Association 235: 1450–5

Bartges JW, Kirk C and Lane IF (2004) Update: Management of calcium oxalate uroliths in dogs and cats.. The Veterinary Clinics of North America. Small Animal Practice 34: 969–87

Bartges JW, Osborne CA, Lulich JP, Kirk C, Allen TA and Brown C (1999) Methods for Evaluating Treatment of Uroliths. Veterinary Clinics of North America: Small Animal Practice 29: 45–57

Buffington TCA and Chew DJ (2009) Calcium Oxalate Urolithiasis in Cats. Journal of Endourology 13: 659-663

Bushinsky DA, Grynpas MD, Nilsson EL, Nakagawa Y and Coe FL (1995) Stone formation in genetic hypercalciuric rats. Kidney International 48: 1705–1713

Cannon AB, Westropp JL, Ruby AL and Kass PH (2007) Evaluation of trends in urolith composition in cats: 5,230 cases (1985-2004). Journal of the American Veterinary Medical Association 231: 570–6

Dijcker JC, Plantinga EA, van Baal J and Hendriks WH (2011) Influence of nutrition on feline calcium oxalate urolithiasis with emphasis on endogenous oxalate synthesis. Nutrition Research Reviews 24: 96–110

Goodman HO, Holmes RP and Assimos DG (1995) Genetic factors in calcium oxalate stone disease.. The Journal of Urology 153: 301–7

Kirk CA, Ling G V, Franti CE and Scarlett JM (1995) Evaluation of factors associated with development of calcium oxalate urolithiasis in cats.. Journal of the American Veterinary Medical Association 207: 1429–34

Lekcharoensuk C, Lulich JP, Osborne CA, Koehler LA, Urlich LK, Carpenter KA and Swanson LL (2000) Association between patient-related factors and risk of calcium oxalate and magnesium ammonium phosphate urolithiasis in cats. Journal of the American Veterinary Medical Association 217: 520–525

Lyons LA (2010) Feline genetics: clinical applications and genetic testing. Topics in Companion Animal Medicine 25: 203–12

McClain HM, Barsanti JA and Bartges JW (2014) Hypercalcemia and calcium oxalate urolithiasis in cats: a report of five cases. Journal of the American Animal Hospital Association 35: 297–301

Picavet P, Detilleux J, Verschuren S, Sparkes A, Lulich J, Osborne C, Istasse L and Diez M (2007) Analysis of 4495 canine and feline uroliths in the Benelux. A retrospective study: 1994-2004. Journal of Animal Physiology and Animal Nutrition 91: 247–51

Thumchai R, Lulich J, Osborne CA, King VL, Lund EM, Marsh WE, Ulrich LK, Koehler LA and Bird KA (1996) Epizootiologic evaluation of urolithiasis in cats: 3,498 cases (1982-1992). Journal of the American Veterinar

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