History

Dog Urinary Tract Health

Key Message

WALTHAM has contributed to the understanding of urinary tract health in dogs by:

  • Developing novel methodologies for urine collection and analysis.
  • Discovering that the increased risk of urolithiasis in smaller breeds is in part because they pass more concentrated urine with a higher pH less often than larger breed dogs.
  • Demonstrating the benefits of urinary dilution through dietary moisture (small dogs) and dietary sodium (all dogs), and generating insights around the benefits of wet foods for urinary tract health in small dogs.
  • Establishing that dietary calcium is relatively more important than dietary oxalate in influencing the risk of calcium oxalate formation in small breed dogs.
  • Demonstrating that a diet with controlled levels of dietary calcium and oxalate reduces the risk of calcium oxalate urolith recurrence in dog.

Background

Urolithiasis can be defined as the 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. In dogs, uroliths are most commonly found in the bladder; kidney uroliths have also been diagnosed, but to a far lesser extent. Uroliths form when urine becomes supersaturated with respect to the ionic components of a specific stone type, leading to crystal precipitation, coagulate and growth.

Factors influencing the risk of urolithiasis in dogs include the concentration of the solutes involved, urine pH, 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). Breed, age and sex can also have a significant effect (Ling et al. 2003).

Although urinary crystals are frequently associated with clinical signs of cystitis, the presence of crystals in urine does not itself cause disease, and crystalluria can occur in healthy dogs that never go on to develop lower urinary tract disease. However, implementing strategies that help reduce or prevent crystal formation will greatly reduce the risk of urolithiasis and will support effective disease management in clinical cases.

The most common uroliths in dogs are composed of calcium oxalate or struvite (magnesium ammonium phosphate) (Ling et al. 2003; Rogers et al. 2011; Markwell et al. 2000). 

Calcium oxalate

Calcium oxalate urolithiasis is increasingly important in dogs. From 1981 to 2001, the proportion of canine uroliths containing calcium oxalate rose from 1% to 31% of submissions in females and 18% to 82% in male dogs (Ling et al. 2003). Similarly, calcium oxalate submissions increased relative to other stone types at a Canadian laboratory between 1998 and 2008 (Houston and Moore 2009). Calcium oxalate uroliths are particularly prevalent in small breed male dogs (Houston and Moore 2009) of middle to old age (Stevenson and Rutgers 2006). 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. Current thinking suggests that calcium oxalate uroliths can form across the physiological urine pH range indicating that control of urine pH is not a critical factor in managing and reducing the risk of calcium oxalate formation in dogs (Stevenson and Rutgers 2006).

Calcium Oxalate Crystals

Figure 1:  Calcium oxalate crystals

Calcium Oxalate Uroliths

Figure 2: 100% calcium oxalate uroliths – male dachshund, 7 years of age

Struvite

The relative incidence of this urolith type has declined in recent decades as the percentage of calcium oxalate has increased (Osborne et al. 2009). Struvite stones are most common in young to middle aged female dogs (Stevenson and Rutgers 2006), and in contrast to cats, most (>85%) canine struvite uroliths are associated with urinary tract infection (Markwell et al. 2000). Effective treatment of the bacterial infection is critical. Diet can support effective treatment of struvite urolithiasis, promoting the production of more acidic urine and stone dissolution and reduction of crystal formation. Dietary management for prevention of struvite formation is less relevant in dogs.

Struvite Crystals

Figure 3: Struvite crystals
Struvite urolith

Figure 4: 100% struvite urolith – female Japanese spitz, 7 years of age, entire
Struvite uroliths (2)

Figure 5: 100% struvite uroliths – female cross-breed dog, 7 years of age

Urolithiasis and the role of nutrition

It is possible to influence some of the risk factors associated with calcium oxalate uroliths through diet and feeding regimen. WALTHAM has focussed on understanding the influence of dietary ingredients and feeding patterns on the volume, pH, and solute concentration of the urine in order to support effective disease management or reduce the risk of calcium oxalate formation in dogs. 

Diet can positively impact on the urinary tract health of dogs in two ways:

1.    Therapeutic diets that support the veterinary care of clinical cases with urolithiasis. Existing struvite uroliths can be dissolved when appropriate antimicrobial treatments are used in conjunction with an acidifying diet (Calabrò et al. 2011). To date, calcium oxalate uroliths must be mechanically removed and a therapeutic diet can then be used to reduce the risk of recurrence in susceptible individuals. Diets that encourage urine with a low level of saturation – ideally undersaturated – are ideal for supporting the management of urolithiasis.

2.    Diets that reduce the risk of calcium oxalate formation in healthy dogs. Diets formulated to produce urine within the metastable zone of supersaturation will help maintain urinary tract health in healthy dogs.

Why WALTHAM is Interested

Calcium oxalate urolithiasis is an important cause of urinary tract disease in dogs that has grown in importance over the last few decades. It is important to understand the risk factors and to assess the impact of dietary components such as minerals and moisture content on calcium oxalate urolith formation to help develop diets that reduce the risk of, 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 calcium oxalate formation. 

Key areas of investigation within this programme include uncovering reasons why smaller breeds may be at greater risk of calcium oxalate urolithiasis, assessing the relative influence of dietary calcium and dietary oxalate intake on the risk of calcium oxalate formation, and investigating the benefits of urine dilution on urinary tract health.

Capability Development (Urine Collection)

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

A system was developed to collect naturally voided urine samples. When the dogs at WALTHAM are participating in studies, they may be housed individually in purpose-built pens. This set-up was modified for urine collection, with each pen comprising two rooms – one floored with vinyl that provided a sleeping and feeding area, and the other comprising a large fibreglass tray (Stevenson et al. 1998). The tray slopes so that urine rapidly drains through a hole in one corner into a collection bottle beneath. The dogs are readily trained to urinate on the 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 (Stevenson et al. 1998). The pH probes are connected via pH meters to a computer to log the data. A rise in temperature signals urination and triggers data capture. The system developed for dogs was built upon success in methodology development for cats.

This system has advantages over traditional alternatives such as cystocentisis because it is non-invasive, does not interfere with the dog’s normal urination patterns, and allows the rapid and repeated analysis of pH without storage delays. However, measuring urine pH offers little value for assessing the risk of calcium oxalate formation since calcium oxalate stones can form across the physiological urine pH range.

Dog schematic

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

Relative supersaturation assessment has been regarded as the gold-standard in the human field for decades. However, its adaptation for predicting the crystallisation potential of dog urine is much more recent. WALTHAM utilised the dog urine collection system for both urine pH assessment and to collect urine samples for RSS assessment in dogs (Stevenson et al. 1998).

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 dog urine (Robertson et al. 2002). Two frequently used programs (SUPERSAT and EQUIL2) were evaluated as to their suitability for calculating calcium oxalate and struvite RSS in dog urine (Robertson et al. 2002). EQUIL2 and SUPERSAT both calculated reasonably accurate RSS values for calcium oxalate in dog urine, whereas only SUPERSAT provided an accurate measure of struvite RSS (Robertson et al. 2002). This study suggests that, for dog urine, SUPERSAT is the most accurate and repeatable method for calculating RSS.

Accurate RSS measurement and interpretation underpins the canine 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 (Stevenson and Rutgers 2006).

Zones
Reproduced from Stevenson A, Rutgers C. Nutritional management of canine urolithiasis. In: Encyclopedia of Canine Clinical Nutrition. Eds: Pibot P, Biourge V, Elliott D.2006.Aniwa SAS. Pages 284-315

Figure 7: Zones of urinary relative supersaturation and the crystallisation processes that occur in each zone (Stevenson and Rutgers 2006)

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 (Breed Size)

The increased risk of urolithiasis in smaller breeds is in part because they produce more concentrated urine and urinate less often than larger breed dogs

Data from many urolith analysis centres provides evidence to suggest that smaller breeds of dog such as the Yorkshire terrier, miniature schnauzer, Shih Tzu and Pomeranian are at greater risk of calcium oxalate urolithiasis than larger breeds. However, the reasons for this were unclear.

In phase 1 of a study at WALTHAM, 16 healthy adult dogs (8 Labrador retrievers and 8 miniature schnauzers) were fed the same nutritionally complete dog food for 24 days and their urine was monitored (Stevenson and Markwell 2001). In phase 2, the study was repeated with 8 Labrador retrievers and 7 Cairn terriers (Stevenson et al. 2001).

In phase 1, dogs were monitored continuously over six 48 hour periods enabling construction of diurnal profiles in addition to monitoring urine pH and RSS. In phase 2 only an RSS assessment was conducted.

In phase 1, miniature schnauzers urinated significantly less often than Labrador retrievers producing urine with a lower volume (mL/kg body weight per day) and a significantly higher urine pH (Stevenson and Markwell 2001). When comparing the diurnal profiles miniature schnauzers had a higher urine pH and tended to have a higher specific gravity (mean over 24 hours, 1.030 ±
0.008) than Labrador retrievers (1.023 ± 0.010) through the majority of the 24-hour period (Stevenson and Markwell 2001). In addition, mean daily urinary calcium concentration was significantly higher in the miniature schnauzers (0.93 ± 0.25 compared with 0.61 ± 0.23 for Labradors, P<0.05) (Stevenson and Markwell 2001).

In phase 2, Cairn terriers produced urine with a significantly higher calcium concentration and calcium oxalate RSS (Stevenson et al. 2001).

These findings show that there are differences in urine composition between different breeds of dog fed the same diet. Some of these factors – such as lower urine volume, higher calcium concentration and higher calcium oxalate RSS – seen in small dogs may contribute to the increased prevalence of calcium oxalate urolithiasis in this group.

Discovery (Urinary Dilution)

A moderate level of dietary sodium is an effective strategy for encouraging urinary dilution and reducing the risk of calcium oxalate urolith formation in all dogs. Increasing dietary moisture results in urinary dilution in small breed dogs only 

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.

In this series of studies, a nutritionally complete dry dog food (7% moisture, 0.06 g Na per 100 kcal), supplemented with water (to provide 73% moisture) or sodium (to deliver 0.20 or 0.30 g Na per 100 kcal), was fed to 31 Labradors and miniature Schnauzers for 24–36 days and urinary RSS assessed (Stevenson et al. 2003b).

Dietary sodium

Early studies at WALTHAM showed that dogs (like humans) respond to dietary sodium by drinking more (Burger et al. 1980). Subsequently, it was shown that increased dietary sodium led to the production of urine with a significantly lower calcium oxalate RSS in both Labrador retrievers and miniature Schnauzers (Stevenson et al. 2003b). These data show that a moderate level of dietary sodium can reduce the risk of calcium oxalate formation in large and small breeds of dog.

Graph
Reprinted from Stevenson AE, Hynds WK, Markwell PJ. Effect of dietary moisture and sodium content on urine composition and calcium oxalate relative supersaturation in healthy miniature schnauzers and labrador retrievers. Res Vet Sci. 2003b Apr;74(2):145-51 with permission of Elsevier

Figure 8: The effect of dietary sodium on urinary calcium oxalate RSS in Labrador retrievers (LR, n=7) and miniature Schnauzers (MS, n=8) (Stevenson et al. 2003b). Significant differences within a breed indicated by different superscript letters (P<0.05)

Dietary moisture

In miniature Schnauzers, increasing dietary moisture content increased total moisture intake, and reduced urine specific gravity, urinary oxalate concentration, and calcium oxalate RSS (Stevenson et al. 2003b). In contrast, there was no effect on the urinary concentration of Labradors (Stevenson et al. 2003b), indicating they may regulate water balance more effectively. These data show that small breeds that tend to be at greater risk of calcium oxalate formation may benefit from increased dietary moisture in order to help maintain urinary tract health or manage calcium oxalate urolithasis.

Graph
Reprinted from Stevenson AE, Hynds WK, Markwell PJ. Effect of dietary moisture and sodium content on urine composition and calcium oxalate relative supersaturation in healthy miniature schnauzers and labrador retrievers. Res Vet Sci. 2003b Apr;74(2):145-51 with permission of Elsevier

Figure 9: The effect of dietary moisture on urinary calcium oxalate relative supersaturation in Labrador retrievers (LR, n=7) and miniature Schnauzers (MS, n=8) (Stevenson et al. 2003b). Significant differences within a breed indicated by different superscript letters (P<0.05)

Insight Generation

Feeding 25% of the daily caloric requirement as wet diet is associated with beneficial effects on urinary tract health

The benefit of urinary dilution using dietary moisture in small dogs had been demonstrated (Stevenson et al. 2003b), but the amount of wet diet required to achieve this in practice was unknown.

This study assessed the impact on calcium oxalate RSS of feeding different proportions of wet and dry diets to small dogs in order to identify the proportion of wet format required within the daily ration to elicit a significant urinary tract health benefit (Buckley et al. 2010). A panel of 8 healthy small breed dogs (4 cocker spaniels, 3 miniature Schnauzers and 1 Cairn terrier) were fed four different combinations of wet and dry food in a four phase crossover trial with each phase lasting for 10 days. The diet combinations were A, 100% dry; B, 25% wet calories and 75% from dry; C, 50% wet calories and 50% from dry; and D, 100% wet. Complete data sets were obtained for 5 dogs which contributed to the analyses (Buckley et al. 2010).

Calcium oxalate RSS was significantly reduced in dogs receiving as little as 25% of their calories from wet diet (9.33 ± 3.74) compared with dry diet alone (19.92 ± 7.36) (Buckley et al. 2010). The urinary calcium oxalate RSS of dogs fed on 100% dry diet in this study was categorised as oversaturated (defined as calcium oxalate RSS>12), which is associated with a high risk of spontaneous stone formation and growth of any existing stones (Buckley et al. 2010). Introducing 25% of calories from wet diet results in a metastable supersaturation (calcium oxalate RSS 1–12) where growth of existing stones will not occur and new stone formation is not possible (Buckley et al. 2010). Principal component analysis showed that this effect was largely attributed to the higher sodium and moisture levels contributed by the wet format (Buckley et al. 2010).

RSS CaOx
Reproduced from Buckley C, Colyer A, Thomas G, Stevenson AE. The effect of dietary format on urinary parameters in small breed dogs. The WALTHAM International Nutritional Sciences Symposium 2010[Poster 62]

Figure 10: Mean calcium oxalate relative supersaturation with 95% confidence intervals for different dietary regimens. Same letter indicates no significant difference (Buckley et al. 2010)

This study suggests that feeding as little as 25% of the daily food ration as wet diet is associated with beneficial effects on urinary tract health.

Discovery (Dietary Calcium and Oxalate)

Dietary calcium is relatively more important than dietary oxalate in influencing the risk of calcium oxalate urolithiasis in dogs

The main risk factors for calcium oxalate urolithiasis are urinary supersaturation with calcium and oxalate. Urinary concentrations of both calcium and oxalate may be influenced by dietary intakes. It is important to understand the relative importance of dietary calcium and oxalate contents on urinary tract health in order to develop diets for prevention and treatment of the disease.

A study at WALTHAM assessed the relative effects of dietary calcium and oxalate on the urine composition of 7 miniature Schnauzers and Cairn terriers (Stevenson et al. 2003a). For 24 weeks, they were fed a nutritionally complete dry dog food supplemented with different combinations of dietary calcium and oxalate (in the form of oxalic acid) commonly found in dry commercially-prepared dog foods.

Urinary calcium concentration increased significantly with dietary calcium content (Stevenson et al. 2003a). Urinary oxalate increased, although inconsistently, with dietary oxalic acid only when the dietary calcium content was low (Stevenson et al. 2003a). Calcium oxalate RSS was lowest when both dietary calcium and oxalate were low, and was highest when dietary calcium content was high and dietary oxalate content was low (Stevenson et al. 2003a). Although the data showed variability, a low calcium diet with increased dietary oxalate also tended to increase calcium oxalate RSS (Stevenson et al. 2003a).

This study showed that dietary calcium is relatively more important than dietary oxalate in the risk of calcium oxalate urolithiasis. However, both dietary calcium and oxalate contents require consideration, since a reduction in dietary calcium without a concomitant decrease in dietary oxalate may increase the risk of calcium oxalate crystallisation in susceptible dogs.

Discovery (Calcium and Oxalate Dietary Levels)

A diet with controlled levels of calcium and oxalate reduces the risk of recurrence in calcium oxalate stone forming dogs

The benefits of a canned, moderately-acidifying diet with controlled levels of calcium and oxalate have been shown in several studies with dogs that have a history of calcium oxalate urolithiasis.

In collaboration with the Institute of Urology and Nephrology in London, a clinical study was conducted to investigate whether there were differences in dietary nutrient intakes or urine composition between 17 calcium oxalate stone-forming dogs and 17 age-, breed-, and sex-matched healthy dogs (Stevenson et al. 2004). All stones were surgically removed at the dog’s usual veterinary practice. Diet diaries were kept for these client-owned dogs for 1 week and an initial 24-hour urine sample was collected. The dogs were then fed a commercially-available canned acidifying diet for 1 month before providing another urine sample.

At baseline, stone-forming dogs had significantly lower dietary intakes of sodium, potassium, calcium, and phosphorus and significantly higher urinary calcium and oxalate concentrations and calcium oxalate RSS (Stevenson et al. 2004). After 1 month on the treatment diet, intakes of moisture, sodium and fat were increased, and potassium and calcium intakes were decreased, and urinary calcium and oxalate concentrations and calcium oxalate RSS were decreased (Stevenson et al. 2004). Follow up urine samples were collected at 3 months, 6 months and 12 months. There were no clinical signs of disease recurrence in these calcium oxalate stone-forming dogs during 12 months’ feeding of the diet (Stevenson et al. 2004).

This study demonstrated that feeding a high-moisture, moderately-acidifying diet with controlled levels of calcium and oxalate to dogs that have formed calcium oxalate uroliths had beneficial effects on urine parameters and helped prevent recurrence for the 12 months they were under observation.

References

Buckley C, Colyer A, Thomas G, Stevenson A. The effect of dietary format on urinary parameters in small breed dogs. The WALTHAM International Nutritional Sciences Symposium 2010: Pet Nutrition – Art or Science? Cambridge, UK September 16-18th 2010. [Poster 62, abstracts page 118].


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.


Calabrò S, Tudisco R, Bianchi S, Grossi M, De Bonis A, Isabella Cutrignelli M. Management of struvite uroliths in dogs. Br J Nutr. 2011 Oct;106 Suppl 1:S191-3.


Houston DM, Moore AE. Canine and feline urolithiasis: examination of over 50 000 urolith submissions to the Canadian veterinary urolith centre from 1998 to 2008. Can Vet J. 2009 Dec;50(12):1263-8.


Ling GV, Thurmond MC, Choi YK, Franti CE, Ruby AL, Johnson DL. Changes in proportion of canine urinary calculi composed of calcium oxalate or struvite in specimens analyzed from 1981 through 2001. J Vet Intern Med. 2003 Nov-Dec;17(6):817-23.


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, Preminger GM. 2000;2;785-788


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):183-97.


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


Stevenson A, Rutgers C. Nutritional management of canine urolithiasis. In: Encyclopedia of Canine Clinical Nutrition. Eds: Pibot P, Biourge V, Elliott D. 2006, Aniwa SAS. pages 284-315.


Stevenson AE, Blackburn JM, Markwell PJ, Robertson WG. Nutrient intake and urine composition in calcium oxalate stone-forming dogs: comparison with healthy dogs and impact of dietary modification. Vet Ther. 2004 Fall;5(3):218-31.


Stevenson AE, Hynds WK, Markwell PJ. The relative effects of supplemental dietary calcium and oxalate on urine composition and calcium oxalate relative supersaturation in healthy adult dogs. Res Vet Sci. 2003a Aug;75(1):33-41.


Stevenson AE, Hynds WK, Markwell PJ. Effect of dietary moisture and sodium content on urine composition and calcium oxalate relative supersaturation in healthy miniature schnauzers and labrador retrievers. Res Vet Sci. 2003b Apr;74(2):145-51.


Stevenson AE, Hynds WK, Markwell PJ. A comparison of urine composition of labrador retrievers and cairn terriers. J Vet Intern Med. 2001:15(3)316 [Abstract 177]


Stevenson AE, Smith BH, Markwell PJ. A system to monitor urinary tract health in dogs. J Nutr. 1998 Dec;128(12 Suppl):2761S-2S.


Stevenson AE, Markwell PJ. Comparison of urine composition of healthy Labrador retrievers and miniature schnauzers. Am J Vet Res. 2001 Nov;62(11):1782-6.

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