Karyl J. Hurley DVM, DACVIM, DECVIM, Waltham Centre for Pet Nutrition, UK
Abigail Stevenson BSc (Hons), GIBiol, PhD, Waltham Centre for Pet Nutrition, UK
Hilary Watson BSc (AGR), Waltham USA, Inc
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Why is measuring relative supersaturation useful?
In order to develop diets which effectively manage both struvite and calcium oxalate urolithiasis in pets, Waltham scientists have explored more complex research methods for predicting urolithiasis risk in dogs and cats (1). The predominant urolith in humans is calcium oxalate, and more than 30 years ago, human urologists began looking at ways of predicting the risk of calcium oxalate urolith formation in their human patients. The result was the development of a research methodology known as RSS or relative supersaturation (2). RSS evaluation has been the gold standard for urine assessment in humans for three decades and has been proven to be the only reliable predictor of the risk of calcium oxalate urolithiasis (3). Waltham scientists, working in conjunction with W. D. Robertson, the originator of human RSS methodology, have adapted this methodology for the evaluation of dog and cat urine. This methodology involves the analysis of 12 constituents of a collected urine sample, as well as the determination of urine pH. These data are then analyzed using a computer program which calculates the concentrations of the large number of interactive complexes between all ions present in this urine. Finally, the program calculates the activity product of the urine sample for a given urolith and divides this number by the known constant thermodynamic solubility product for that urolith to determine RSS.
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Research findings which have been made possible by RSS methodology:
- It is possible for a single diet to manage both types of uroliths (4)
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- It is possible to undersaturate for calcium oxalate with an acidifying diet (4)
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- Increased sodium content does not increase urinary excretion of calcium and therefore is not a risk factor for calcium oxalate in dogs (5)
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- Increasing urine pH above the safe range for struvite (i.e. 6.6–6.8), does not lower the risks of calcium oxalate formation but does increase the risk of struvite formation (6)
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- Potassium citrate does not lower the risk of calcium oxalate formation in dogs, but may increase the risk of struvite formation in some dogs (7)
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How does the RSS relate to dietary intake?
The dietary components can alter the concentration of all urinary constituents which may ultimately combine to form crystals, plugs, and uroliths. Therefore, diets formulated to target appropriate RSS ranges can be used to:
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- Dissolve and prevent recurrence of struvite uroliths
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- Prevent reformation of the mineral (struvite) component of urethral plugs and, therefore, reduce recurrence of obstruction
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- Reduce the risk of development and recurrence of calcium oxalate uroliths
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- Reduce the recurrence of signs in cats with idiopathic cystitis
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- Reduce the risk of struvite and calcium oxalate formation in cats
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Why not just measure pH?
Historically, when the main interest in feline lower urinary tract diseases was focused on controlling struvite formation, pH was important. Measurement of urinary pH thus provided the best tool at the time for both the development and monitoring of diets aimed at controlling struvite formation. More recent research has demonstrated that urine pH is not even in itself a reliable indicator of struvite urolithiasis risk (Figure 1). Unfortunately, the urine pH is even less reliable for assessing the crystallization potential of urine with respect to calcium oxalate because pH does not significantly affect calcium oxalate crystallization over the normal range of urinary pH. Calcium oxalate uroliths can form within the full range of normal urine pH in humans, i.e. 4.8–7.4, and evaluating urine pH is not relevant to assessing calcium oxalate risk despite concerns regarding acidifying diets (Figure 2). In the last 20 years, the incidence of calcium oxalate uroliths in both cats and dogs in North America has increased to account for nearly half of the uroliths recovered; therefore, a more advanced method of evaluating urine in order to prevent urolith formation was needed.
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Although more complicated than the historical approach of simply assessing urine pH, RSS is a much more powerful tool which is considered the gold standard for urine assessment in humans and is now so in cats and dogs as well. Its value derives from the fact that a single value incorporates all parameters which influence the likelihood of a particular urolith type forming: urine pH, urine dilution, all relevant urine constituents, and the possible interactions between them. RSS is a single value which can be used to describe the efficacy of a given diet in managing urolithiasis in pets.
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What does the RSS value mean?
There are three clearly defined zones of urinary relative supersaturation (RSS) (Figures 3a and 3b). The same zones and RSS values apply to the urine of both cats and dogs:
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1. Zone of undersaturation
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Urine below the solubility product for a given salt is termed undersaturated. If urine is maintained within this zone uroliths cannot form. Regardless of the stone type (i.e struvite, calcium oxalate, calcium phosphate etc.) undersaturated urine will have an RSS <1.0. Any existing struvite crystals or uroliths added to urine in this state will dissolve. Although it is not possible to dissolve pre-existing calcium oxalate, they will not grow or reform in pre-disposed animals in this environment. Products formulated for dogs and cats with lower urinary tract disorders using Waltham Science target creation of urine in this zone of saturation.
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2. Zone of metastable supersaturation
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As with humans the urine of normal healthy dogs and cats can often fall within the zone of metastable saturation.
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In this zone, new struvite or calcium oxalate uroliths will not form, however, any existing struvite uroliths will not dissolve and may grow. Where: formation product = the ability for a known concentration of ions to dissolve in a known volume of liquid at a set temperature and pH, a chemically derived thermodynamic constant, and solubility product = the concentration of ions at which homogeneous precipitation occurs, the RSS values for the metastable zone are as follows: calcium oxalate RSS between 1 and 12, struvite RSS between 1 and 2.5.
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3. Zone of oversaturation
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Urine with a solute activity product that exceeds the formation product falls within the zone of oversaturation. This is a highly unstable environment in which spontaneous homogeneous crystal formation, aggregation, and growth occurs. Within this zone uroliths would be expected to form and grow. RSS values which correspond with the zone of oversaturation are as follows: calcium oxalate RSS >12, struvite RSS >2.5.
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How does this method compare with other techniques?
RSS evaluation has allowed scientists to assess several longstanding hypotheses regarding the management of urolithiasis in dogs and cats and has resulted in several widely held theories being definitively refuted (Table 1).
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References
1. Smith, B. H. E., Stevenson, A. E., Markwell, P. J., Urinary relative supersaturations of calcium oxalate and struvite in cats are influenced by diet. Journal of Nutrition 1998; 128: 2763S–2764S.
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2. Robertson, W. G., and Markwell, P. J. Predicting the calcium oxalate crystallisation potential of cat urine. Waltham Viewpoint, Waltham Focus 1999; 11.3: 32.
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3. Pak, C. Y. C., Hayashi, Y., Finlayson, B., Chu, S. Estimation of the state of saturation of brushite and calcium oxalate in urine: A comparison of three methods. Journal of Laboratory Clinical Medicine 1977; 89: 891-901.
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4. Smith, B.H.E., Stevenson, A.E., Markwell, P.J. Effect of diet on relative supersaturations in feline urine. Proceedings of the FECAVA Congress1. Smith, B.H.E., Stevenson, A.E., Markwell, P.J. Effect of diet on relative supersaturations in feline urine. Proceedings of the FECAVA Congress, 1995; 350-360.
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5. Stevenson, A. E., Hynds, W. K., Markwell, P. J. Effect of dietary moisture and sodium content on urine composition and calcium oxolate relative composition and calcium oxolate relative supersaturations in healthy minature schnauzers and labrador retrievers. Research in Veterinary Science 2003; 74: 145-151.
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6. Stevenson, A. E., Wrigglesworth, D. J., Markwell, P. J. Urine pH and urinary relative supersaturations in healthy adult cats. Proceedings of the 9th International Symposium; 2000: 818-820
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7. Stevenson, A. E., Wrigglesworth, D. J., Smith, B. H. E., Markwell, P. J. Effects of dietary potassium citrate supplementation on urine pH and oxolate and struvite in healthy dogs. American Journal of Veterinary Research 2000; 61: 430-435
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