History

Cat Urinary Tract Health

Key Message

WALTHAM has contributed to the understanding of urinary tract health in cats through:

  • Development of novel methodologies for urine collection and analysis.
  • Demonstrating that a diet producing moderately acidic urine can minimise the risk of both calcium oxalate and struvite formation in cats.
  • Demonstrating that increasing water intake results in urinary dilution that is beneficial for urinary tract health in cats.
  • Generating insights that indicate that feeding patterns can influence the 24-hour urine pH profile; and that the age of the cat may be a factor influencing urolith type.

Background

Feline lower urinary tract diseases (FLUTD) are characterised by haematuria (blood in the urine), dysuria (painful urination), inappropriate urination, stranguria (the urge to urinate), pollakiuria (frequent urination) and sometimes urethral obstruction (which can rapidly become fatal).

Urological diseases are a common reason for veterinary hospital admissions, involving over 7% of the feline case load (Osborne et al. 1995). One study examining obstructed cats found that 60.4% presented with urethral plug, 11.3% with uroliths and, in the remaining 28.3%, no cause could be found (Osborne et al. 1989). A study in non-obstructed cats reported that 15% of urological cases presented with urolithiasis and other causes of the disease included anatomical abnormalities (11%) and behavioural problems (9%), with idiopathic cystitis diagnosed in 64% (Buffington et al. 1997).

Urolithiasis

Urolithiasis can be defined as formation of sediment anywhere within the urinary tract consisting of one or more poorly soluble crystalloids of urine. The condition starts with the formation of urinary crystals that may, in the right conditions, progress to form uroliths (stones) within the urinary tract. Uroliths are most commonly found in the bladder although kidney uroliths have also been diagnosed but to a far lesser extent. Uroliths form when specific minerals or compounds in supersaturated urine precipitate, and the crystals coagulate and grow.

Factors influencing urolithiasis include the concentration of the solutes (Figure 1), urine pH, urine temperature, genetic or metabolic disorders, lifestyle and body condition, and the presence or absence of various promoters (such as bacteria) and inhibitory factors (such as citrate and pyrophosphate).

solutes
Reproduced from Markwell PJ, Buffington CT, Smith BH. The effect of diet on lower urinary tract diseases in cats. J Nut. 1998 Dec;128(12Supp):2753S-2757S

Figure 1: Some solutes affecting crystallisation in urine (Markwell et al. 1998). Other factors affecting crystal formation include time, temperature, and the presence, absence, and effectiveness of endogenous protein crystallisation inhibitors

Although urinary crystals are frequently associated with the clinical signs of FLUTD, the presence of crystals in urine does not itself cause disease, and crystalluria can occur in healthy cats that never go on to develop FLUTD. However, implementing strategies that help prevent crystal formation will greatly reduce the risk of urolithiasis and the formation of the mineral component of urethral plugs.
 
The most common uroliths in cats are composed of struvite (magnesium ammonium phosphate) or calcium oxalate (Markwell et al. 2000; Rogers et al. 2011).
 
Struvite

This was the most common urolith type found in cats during the 1980s and has recently returned to being the most prevalent urolith (Osborne et al. 2009). Consequently there is considerable literature documenting risk factors and prevention strategies. Struvite can occur at any age and is more common in female cats. Unlike dogs and humans, most feline struvite uroliths tend to form in sterile urine (Houston and Elliott 2008). Controlling urine pH is critical for the management and prevention of struvite as alkaline urine increases the risk of struvite crystallisation and subsequent urolith formation. Increasing urine volume is also important since this will dilute urinary minerals. Although relatively less important than controlling urine pH, levels of dietary minerals (magnesium and phosphorus) may also be important. Examples of struvite crystals (Figure 2) and a struvite urolith (Figure 3) are shown below.


Figure 2: Struvite crystals

struvite urolith

Figure 3: 100% struvite urolith – female cat, 5 years of age

Calcium oxalate

The incidence of this urolith type appeared to increase through the 1980s and 1990s, making up only 2% of uroliths analysed in 1981 but increasing to 55% by 2002 (Osborne et al. 2009). However, by 2007 calcium oxalate occurrence had decreased back to 41% of uroliths submitted for analysis (Osborne et al. 2009). Calcium oxalate is more commonly found in middle aged (mean age 7.8 years), male cats (Houston and Elliott 2008). Increasing water intake resulting in urinary dilution is an important part of reducing the risk of calcium oxalate formation. The role of urine pH in calcium oxalate formation is more controversial. The influence of urine pH on calcium oxalate solubility is low across the physiological pH range and urine pH is a poor predictor of the risk of calcium oxalate formation (Houston and Elliott 2008). Examples of calcium oxalate crystals (Figure 4) and uroliths (Figure 5) are shown below.

Calcium oxalate crystals

Figure 4: Calcium oxalate crystals

100% calcium oxalate uroliths

Figure 5: 100% calcium oxalate uroliths – male cat, 9 years of age, neutered

Urolithiasis and the role of nutrition


It is possible to influence at least some of the risk factors associated with the two most common urolith types through diet and feeding regimen. Dietary ingredients and feeding patterns can influence the volume, pH, and solute concentration of the urine (Markwell et al. 1998). Diet can also influence water balance. Cats being fed dry cat food often produce smaller volumes of more concentrated urine (Markwell et al. 1999a), probably because they take in less total water (Burger et al. 1980).
 
Diet can positively impact on the urinary tract health of cats in two ways:
  1. Therapeutic diets that support the veterinary care of clinical cases with struvite and calcium oxalate urolithiasis. WALTHAM was first to demonstrate that it is possible to formulate a diet that will produce moderately acidic urine that is undersaturated for both struvite and calcium oxalate, thus treating the two most common stone types with one diet. Under these conditions existing struvite uroliths may also be dissolved (Houston et al. 2004) although existing calcium oxalate uroliths must be surgically removed.  
  2. Diets that reduce the risk of struvite and calcium oxalate formation in healthy cats. Diets formulated to produce urine within the metastable zone of saturation will help maintain urinary tract health in healthy cats.

Why WALTHAM is Interested

Urolithiasis is an important lower urinary tract disease in cats (Markwell et al. 1998) that can be modulated through diet. It is important to understand the impact of dietary components such as minerals and moisture content on struvite and calcium oxalate urolith formation in order to help develop diets that reduce the risk or aid in the management of this disease.

Approach

For studies investigating the influence of nutrition on the risk of urolithiasis an ethical method of urine collection was required that allowed repeated assessment of naturally voided urine. This methodology allows constant urine pH monitoring and relative supersaturation assessment, critical for establishing the influence of diet on the risk of struvite and calcium oxalate formation.

Key areas of investigation within this programme include the influence of urinary pH on the risk of urolith formation and the benefits of increasing moisture intake, through feeding wet foods or through dietary sodium manipulation as a way of encouraging cats to drink more.

Capability Development

In order to investigate urinary tract health, WALTHAM developed a novel methodology for collecting urine samples from cats, enabling pH monitoring and relative supersaturation (RSS) assessment

A system was developed to collect naturally voided urine samples (Markwell and Smith 1993). When the cats at WALTHAM are participating in studies, they may be housed individually in purpose-built lodges. The litter trays are designed with a sloped base so that urine rapidly drains through a hole in one corner into a collection bottle beneath. The cats are readily trained to use these litter trays by gradually reducing the amount of litter over a period of weeks until the cat is happy to urinate directly onto the sloping tray. This set-up allows the non-invasive collection of urine samples. It can also be modified to freeze the urine as soon as it is voided to enable RSS assessment.

Urine pH monitoring

In order to monitor pH, urine passes through a purpose built glass U-tube containing a temperature/pH probe over which urine passes on its way to the collection bottle (Markwell and Smith 1993). The pH probes are connected via pH meters to a computer to log the data (Figure 6). A rise in temperature signals urination and triggers data capture.
This system has advantages over traditional alternatives such as cystocentisis because it is non-invasive, does not interfere with the cat’s normal urination patterns and allows the rapid and repeated analysis of pH without storage delays.

Schematic diagram of the WALTHAM system for monitoring urine pH in cats

Figure 6: Schematic diagram of the WALTHAM system for monitoring urine pH in cats

Relative Supersaturation

Relative supersaturation (RSS) assessment has been regarded as the gold-standard in the human field for decades. However, its adaptation for predicting the crystallisation potential of cat urine is much more recent. WALTHAM utilised the urine collection system initially used for urine pH assessment (Markwell and Smith 1993) and modified it to collect urine samples for RSS assessment in cats (Markwell et al. 1999b).

In collaboration with Dr WG Robertson, a world-leading human urologist at University College London, WALTHAM researchers validated the methodology for measurement of RSS of cat urine (Robertson et al. 2002). Two programs (SUPERSAT and EQUIL2) were evaluated as to their suitability for calculating calcium oxalate and struvite RSS in cat urine (Robertson et al. 2002). EQUIL2 and SUPERSAT both calculated reasonably accurate RSS values for calcium oxalate in cat urine, whereas only SUPERSAT provided an accurate measure of struvite RSS (Robertson et al. 2002). This study suggests that, for cat urine, SUPERSAT is the most accurate and repeatable method for calculating RSS.

Accurate RSS measurement and interpretation underpins the feline urinary tract health research programme at WALTHAM. All researchers in the field agree that urine has to be over(super)saturated with at least one stone-forming mineral for uroliths to form. RSS falls within three definable zones of relative supersaturation (Figure 7 Houston and Elliott 2008).

WDC78 Zones of urinary
Reproduced from Houston DM, Elliott DA. Nutritional management of feline lower urinary tract disorders. In: Encyclopedia of Feline Clinical Nutrition. Eds: Pibot P, Biourge V, Elliott D.2008.Aniwa SAS, France. Pages 285-322

Figure 7: Zones of urinary relative supersaturation and the crystallisation processes that occur in each zone (Houston and Elliott 2008)

Zone of undersaturation

Any crystals added to urine in this state will dissolve. If urine is maintained within this zone uroliths cannot form.

Zone of metastable supersaturation


Urine of normal healthy subjects is often in this zone and crystals can be passed with no harm. As the level of metastable saturation approaches the formation product the length of time before crystallisation commences is reduced. The time between urine formation and crystallisation may also be shortened by the presence of nucleating material such as cell debris or crystals of other mineral types. Any pre-existing crystals are likely to grow in the metastable zone.

Zone of oversaturation

This is a highly unstable environment in which spontaneous crystal formation occurs along with crystal clumping and growth. Within this zone urolith formation is highly likely.

Discovery (Urinary Dilution)

Dietary sodium and dietary moisture are effective strategies for urinary dilution and reducing the risk of calcium oxalate urolith formation

The simplest way of reducing RSS and therefore the risk of urolithiasis is through increasing urine volume. In humans low urine volume has been established as a risk factor for stone formation. WALTHAM investigated two approaches to increasing urine volume through increasing water intake: namely dietary sodium and dietary moisture.

Dietary sodium

Early studies showed that cats (like humans) respond to dietary sodium chloride (salt) by drinking more (Burger et al. 1980). More recently, WALTHAM assessed the effect of dietary sodium content on the water intake and urine composition of adult cats (6 in each group) fed 23 commercially-available dry diets for 21 days (Hawthorne and Markwell 2004). Cats fed diets with higher sodium content had a significantly higher water intake and urine volume, significantly lower urine specific gravity, and significantly lower RSS for calcium oxalate (Figure 8) (Hawthorne and Markwell 2004). Urine pH was not affected. These data show that, even within the range of sodium intakes provided by standard diets, those with a higher sodium content increase water intake and reduce RSS for calcium oxalate.?

Fig21 Dietry sodium content
Reproduced from Houston DM, Elliott DA. Nutritional management of feline lower urinary tract disorders. In: Encyclopedia of Feline Clinical Nutrition. Eds: Pibot P, Biourge V, Elliott D.2008.Aniwa SAS, France. Pages 285-322

Fig22 Dietry sodium content
Reproduced from Houston DM, Elliott DA. Nutritional management of feline lower urinary tract disorders. In: Encyclopedia of Feline Clinical Nutrition. Eds: Pibot P, Biourge V, Elliott D.2008.Aniwa SAS, France. Pages 285-322

Fig23 Dietary sodium content
Reproduced from Houston DM, Elliott DA. Nutritional management of feline lower urinary tract disorders. In: Encyclopedia of Feline Clinical Nutrition. Eds: Pibot P, Biourge V, Elliott D.2008.Aniwa SAS, France. Pages 285-322

Figure 8: The effect of dietary sodium on water intake, urine specific gravity, and calcium oxalate RSS (Houston and Elliott 2008; redrawn from Hawthorne and Markwell 2004)

Dietary moisture

In a study published in 2011 WALTHAM investigated the influence of dietary moisture content on urine parameters and total daily fluid intake in healthy adult cats using nutritionally standardised diets that varied only in moisture content (Buckley et al. 2011). In this study, 6 adult cats were fed a dry diet hydrated to 6.3%, 25.4%, 53.2% or 73.3% moisture in a randomised block crossover design. Cats fed the highest moisture diet produced urine with a lower specific gravity than the other three diets indicating a urinary dilution effect (Buckley et al. 2011). Calcium oxalate RSS was significantly lower in cats fed this diet when compared with the 6.3% moisture diet. Total fluid intake (combined dietary and voluntarily drunk water) was also significantly increased in cats fed the high moisture diet. The 73.3% diet resulted in a significantly higher total daily fluid intake (Figure 11), and production of more dilute urine with a lower risk of calcium oxalate urolith formation when compared to a low moisture diet (Buckley et al. 2011).

Effect of dietary moisture
Reproduced from Buckley CMF, Hawthorne A, Colyer A, Stevenson AE. Effect of dietary water intake on urinary output, specific gravity and relative supersaturation for calcium oxalate and struvite in the cat. Br J Nut 2011 S128-S130 http://journals.cambridge.org/abstract_S0007114511001875

Figure 9: Effect of dietary moisture on total water intake (Buckley et al. 2011). Values are means with 95% CI represented by vertical bars. Different letter indicates significant difference

Discovery (One Diet: Two Urolith Types)

One diet can be used to minimise the risk of both struvite and calcium oxalate formation in cats

Urinary acidification has long been established as a suitable approach for managing and minimising struvite formation in cats. The effect of urine pH on calcium oxalate formation is more controversial and dietary methods for managing calcium oxalate formation were poorly understood.

In an initial study, 6 adult cats were fed an acidifying, high moisture, relatively low magnesium diet for 10 days and urine collected for 48 hours in the second week (Smith et al. 1995). This diet produced urine undersaturated with struvite and calcium oxalate in all cats (Smith et al. 1995). The overall mean urine pH was 6.23 ± 0.42 (Smith et al. 1995). Mean relative supersaturation was 0.17 ± 0.13 for struvite and 0.36 ± 0.23 for calcium oxalate (Smith et al. 1995). This study was the first indication that it was possible to formulate a diet that produced moderately acidic urine understaurated for calcium oxalate and struvite.

Subsequently, the effect of dietary acid load on urine pH and relative supersaturation of calcium oxalate and struvite was investigated in healthy cats. Six adult cats were fed three diets in a latin square design: a nutritionally complete canned cat food (control), the control diet plus ammonium chloride (a urinary acidifier) and the control diet plus sodium bicarbonate (a urinary alkaliniser) (Stevenson et al. 2000). The control diet produced moderately acidic urine that was undersaturated for both calcium oxalate and struvite. Addition of sodium bicarbonate resulted in a significantly higher urine pH with an increased risk of struvite formation (Table 1). Addition of ammonium chloride resulted in urine with a trend towards a more acidic pH and a significantly higher calcium oxalate risk. (Table 1)

Table 1: Effect of urinary acidifier (ammonium chloride, NH4Cl) or alkaliniser (sodium bicarbonate, NaHCO3) compared with control diet (C) on RSS and urine pH; mean for 6 cats (Stevenson et al. 2000).

Effect of urinary acidifier
Adapted from Stevenson AE, Wrigglesworth DJ, Markwell PJ. Urine pH and urinary relative supersaturation in healthy adult cats. Urolithiasis 2000: 9th International Symposium on urolithiasis, 13-17th February, University of Cape Town. Eds: Rodgers AL, Hibbert BE, Hess B, Khan SR, Preminger GM. 2000;2:818-820


This study clearly demonstrates that a moderately acidic urine pH results in the lowest risk of both calcium oxalate and struvite RSS.

Insight Generation

Small meals fed throughout the day maintain a more constant urine pH compared with less frequent large meals

Data from WALTHAM show that small meals fed throughout the day appear to maintain a more constant urine pH profile and minimise the ‘alkaline tide’ effect in cats compared to less frequent large meals (Figures 10 Markwell and Smith 1993).

This provides an insight into practical measures that may help maintain a consistently acidic urine pH over 24 hours, and may help support dietary management of cats at risk of struvite urolithasis. The daily calorie requirement should be delivered via small meals rather than unlimited free access which may result in increased calorie intake.

diurnal variation
Reproduced from Markwell PJ, Smith BHE. An effective urine pH monitoring system for cats. Animal Technol.1993;44(3):239-245

Mean diurnal variation
Reproduced from Markwell PJ, Smith BHE. An effective urine pH monitoring system for cats. Animal Technol.1993;44(3):239-245

Figure 10: Normal diurnal variation in cat urine pH (Markwell and Smith 1993). The top graph shows the alkaline tide 4–6 hours postprandial following a single meal of a canned diet fed at 11.30 am. The bottom graph shows no rise in pH when cats are fed three meals a day on a dry diet designed to acidify urine

Kittens produce more acidic urine than adult cats and therefore, feeding acidifying diets to young cats is not recommended


A pilot study comparing the urine pH of 8-week-old kittens with adult cats (mean age 3.7 years) fed the same commercially-available canned kitten food found that the kittens produced a significantly lower urine pH than adults (Skinner et al. 1995). By 12 weeks of age the urine pH of the kittens was similar to that of the adults. Since young cats naturally produce more acidic urine and are additionally at low risk of struvite formation, the use of acidifying diets should be avoided (Skinner et al. 1995).

Senior cats have a lower risk of struvite formation and a higher risk of calcium oxalate formation compared with younger adult cats

A pilot study compared urine pH and RSS of senior cats (aged 10.6 ± 1.3 years) with younger adult cats (4.1 ± 1 years) (Smith et al. 1997). The study found that the older cats produced more acidic urine (6.1 ± 0.2 vs 6.4 ± 0.2) with a lower struvite RSS and a higher calcium oxalate RSS. This study indicates that age may be a factor influencing the type of urolith formed with younger cats at greater risk of struvite formation and older cats at greater risk of calcium oxalate formation.

Discovery (Idiopathic Cystitis)

Diet can influence idiopathic cystitis recurrence rate

In collaboration with Prof Tony Buffington at the Ohio State University, WALTHAM investigated the role of diet in the management of idiopathic cystitis in cats.

Idiopathic cystitis is often the diagnosis when the cat presents with signs of FLUTD and all known underlying causes are ruled out. Signs of idiopathic cystitis may spontaneously disappear with or without treatment and often recur within weeks or months after initial presentation.

In this study, 54 client-owned cats diagnosed with idiopathic cystitis were fed a commercially-available acidifying diet, either as the canned or dry formulation, for up to 12 months (Markwell et al. 1999a). During that time the cats underwent repeated clinical examination and urinalysis. The proportion of cats with recurrence of lower urinary tract disease was signi?cantly less in those fed the canned diet (11%) compared with the dry formulation (39%) (Markwell et al. 1999a). Recurrence rates of cats on the dry formulation were similar to those reported in studies examining other treatment regimens.

Thus, the canned diet appeared to reduce the recurrence rate of cats suffering from idiopathic cystitis. The reason for this reduction has not yet been established. However, it is likely to be a consequence of a higher moisture intake that resulted in production of more dilute urine (Markwell et al. 1999a).

References

Buckley CM, Hawthorne A, Colyer A, Stevenson AE. Effect of dietary water intake on urinary output, specific gravity and relative supersaturation for calcium oxalate and struvite in the cat. Br J Nutr. 2011 Oct;106 Suppl 1:S128-30.


Burger IH, Anderson RS, Holme DW. Nutritional factors affecting water balance in the dog and cat. In: Nutrition of the Dog and Cat. Editor: RS Anderson. Pergamon Press, Oxford. 1980, pages 145-156.


Buffington CA, Chew DJ, Kendall MS, Scrivani PV, Thompson SB, Blaisdell JL, Woodworth BE. Clinical evaluation of cats with nonobstructive urinary tract diseases. J Am Vet Med Assoc. 1997 Jan 1;210(1):46-50.


Hawthorne AJ, Markwell PJ. Dietary sodium promotes increased water intake and urine volume in cats. J Nutr. 2004 Aug;134(8 Suppl):2128S-2129S.


Houston DM, Rinkardt NE, Hilton J. Evaluation of the efficacy of a commercial diet in the dissolution of feline struvite bladder uroliths. Vet Ther. 2004 Fall;5(3):187-201.


Houston DM, Elliott DA. Nutritional management of feline lower urinary tract disorders. In: Encyclopedia of Feline Clinical Nutrition. Eds: Pibot P, Biourge V, Elliott D. 2008, Aniwa SAS, France. pages 285-322.


Markwell PJ, Robertson WG, Stevenson AE. Urolithiasis: a comparison of humans, dogs and cats. Urolithiasis 2000: 9th International Symposium on urolithiasis, 13-17th February, University of Cape Town. Eds: Rodgers AL, Hibbert BE, Hess B, Khan SR, Preming


Markwell PJ, Buffington CA, Chew DJ, Kendall MS, Harte JG, DiBartola SP. Clinical evaluation of commercially available urinary acidification diets in the management of idiopathic cystitis in cats. J Am Vet Med Assoc. 1999a Feb 1;214(3):361-5.


Markwell PJ, Smith BHE, McCarthy KP. A non-invasive method for assessing the effect of diet on urinary calcium oxalate and struvite relative supersaturation in the cat. Anim Technol. 1999b;50(2):61-67.


Markwell PJ, Buffington CT, Smith BH. The effect of diet on lower urinary tract diseases in cats. J Nutr. 1998 Dec;128(12 Suppl):2753S-2757S.


Markwell PJ, Smith BHE. An effective urine pH monitoring system for cats. Anim Technol. 1993;44(3):239-245.

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Osborne CA, Lulich JP, Kruger JM, Ulrich LK, Koehler LA. Analysis of 451,891 canine uroliths, feline uroliths, and feline urethral plugs from 1981 to 2007: perspectives from the Minnesota Urolith Center. Vet Clin North Am Small Anim Pract. 2009 Jan;39(1):


Osborne CA, Kruger JM, Lulich JP, Polzin DJ. Disorders of the feline lower urinary tract. In: Canine and Feline Nephrology and Urology. Eds: Osborne CA, Finco DR. Philadelphia, Lea and Febiger. 1995. Pages 625-680.


Osborne CA, Polzin DJ, Kruger JM, Lulich JP, Johnston GR, O'Brien TD. Relationship of nutritional factors to the cause, dissolution, and prevention of feline uroliths and urethral plugs. Vet Clin North Am Small Anim Pract. 1989 May;19(3):561-81.


Robertson WG, Jones JS, Heaton MA, Stevenson AE, Markwell PJ. Predicting the crystallization potential of urine from cats and dogs with respect to calcium oxalate and magnesium ammonium phosphate (struvite). J Nutr. 2002 Jun;132(6 Suppl 2):1637S-41S.


Rogers KD, Jones B, Roberts L, Rich M, Montalto N, Beckett S. Composition of uroliths in small domestic animals in the United Kingdom. Vet J. 2011 May;188(2):228-30


Skinner ND, Smith PM. The measurement of urine pH of kittens. Proceedings of the 4th International Conference on Veterinary Perinatology, Cambridge, UK. 1995, page 74


Smith BHE, Moodie SJ, Wensley S, Markwell PM. Differences in urinary pH and relative supersaturation values between senior and young adult cats. J Vet Intern Med. 1997;11(2):127[Abstract 94].


Smith BHE, Stevenson AE, Markwell PJ. Effect of diet on relative supersaturations in feline urine. Proceedings of the 2nd European Congress of the Federation of European Companion Animal Veterinary Associations. Brussels, Belgium 27–29 Oct 1995:359-360.


Stevenson AE, Wrigglesworth DJ, Markwell PJ. Urine pH and urinary relative supersaturation in healthy adult cats. Urolithiasis 2000: 9th International Symposium on urolithiasis, 13-17th February, University of Cape Town. Eds: Rodgers AL, Hibbert BE, Hess


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