Nestlé PURINA Scientific Update on Feline Nutrition Urolithiasis in cats managing the risks
Urolithiasis in cats managing the risks Dr Andrew H Sparkes BVetMed PhD DipECVIM MRCVS Veterinary consultant Simplyfeline Dr Clémentine Jean-Philippe, DVM, Ph.D European Scientific Communication Manager Nestlé PURINA PetCare Urolithiasis and urethral obstruction (due to the presence of small uroliths or urethral plugs which contain crystals) are together the second most common cause of feline lower urinary tract disease (FLUTD), accounting for approximately 1 /3 or more of all cases. These are a significant cause of morbidity in cats, with urethral obstruction causing potentially life-threatening complications associated with obstructive uropathy and acute renal failure. Causes and pathophysiology of urolithiasis The vast majority of feline uroliths are either composed of struvite (magnesium ammonium phosphate) or calcium oxalate. Together these account for around 90% of all uroliths and they occur in roughly equal proportions, although the relative proportion of each type shows some variation over time and some geographical variation too. In contrast to uroliths, the crystals that form an important part of most urethral plugs are nearly always struvite. Nucleation Formation of solid crystal Nucleation A crucial prerequisite for crystal and urolith formation is the production of urine that is supersaturated for the crystalloid components. However, crystal formation and growth is a complex phenomenon affected by factors such as: Frequency and adequacy of bladder emptying Presence of certain mucoproteins, cellular debris or foreign material such as bacteria that can promote crystallisation and formation of a urolith nidus Presence and balance of various promoters and inhibitors of crystallisation in urine (such as nephrocalcin, pyrophosphates, and citrate). Promoters and inhibitors are not the same for all crystalloids magnesium, for example, is a component of struvite and excess thus favours struvite crystal formation, but conversely magnesium helps to inhibit oxalate crystal formation The urine ph again the effect of ph varies between different crystal types Thus while urine supersaturation is crucial for crystallisation, nidus formation, and urolith growth other factors are also important which helps to explain why some individuals appear predisposed to urolithiasis and why there are breed-and gender-related predispositions. Nevertheless, although urolith formation is complex, manipulation (and reduction) of the saturation of urine with the crystalloid materials remains the major method of controlling crystal formation and growth. Urine saturation with crystalloids The degree of urine saturation for any particular crystalloid falls into one of three different zones: Undersaturation in this zone there is insufficient concentration of the crystalloids to allow crystals to form and thus there is no spontaneous crystal formation, no growth of any existing crystals/uroliths, and the potential for existing uroliths and crystals to dissolve. Clinically beneficial dissolution may occur with struvite stones in undersaturated urine, but the rate of dissolution of oxalate stones is so slow that preformed stones invariably have to be removed surgically. Metastable saturation in this zone, although the urine is saturated (above the K SP ) for the particular crystalloid, the concentration is such that spontaneous new crystal formation will not occur. If crystals or stones are already present in the urine they may grow, and heterogenous crystallisation may also occur (existing crystals/uroliths of one type allowing precipitation of another type of crystal around it). Unstable supersaturation this is the most dangerous zone as once the limit of metastability (K FP ) has been exceeded, spontaneous de novo crystal formation and urolith growth can occur. Promoters Crystal aggregation Inhibitors Crystalloid concentration K sp - Saturation product, K fp - Formation product Tissue interaction and crystal retention Stone assembly Spontaneous crystalisation and nucleation K sp Crystal/urolith growth K fp Crystal dissolution Unstable supersaturation Metastable supersaturation Undersaturation Figure 1: Overview of urolith formation Figure 2: Different stages of urine saturation 2 Nestlé PURINA Urolithiasis in cats managing the risks 3
Measurement of urine saturation with crystalloids Two mathematical tools are routinely used to assess the likelihood or risk of stone formation in urine these are: Relative supersaturation (RSS) The RSS values are calculated using various computer software programs after quantifying the soluble mineral load, the concentration of known promoters and inhibitors, the urine ph and the urine volume (i.e. the ionic load of the urolith salt). Values are expressed numerically with higher values indicating a higher risk of crystallization occurring. An RSS of less than one indicates undersaturated urine for both struvite and oxalate. For struvite, the metastable RSS range is between 1 and 2.5, and for oxalate it is thought to be between 1 and 10. Any RSS values above these limits suggest the urine is supersaturated. However, different software programmes generate slightly different RSS values and their accuracy may vary somewhat, dependent in part on what urine components are included in calculations. Activity product ratio (APR) The APR calculations are performed in a semi-empirical manner and do not entirely depend on complex computer derived calculations of ionic activity. Rather, APR values look at the major urinary constituents to calculate an activity product in urine, before and after incubation with a pure seed crystal of the material being evaluated (e.g. struvite or oxalate). In this way, the ratio of the activity products (the APR) is calculated and account is thus taken of all urolith promoters and inhibitors in urine (including those not specifically measured and incorporated into RSS calculations). Any APR value less than 1 indicates undersaturation of the urine and conditions potentially favourable for uroliths to dissolve. An APR value of around 1-2.5 is in the metastable range for struvite and similarly a value between 1-5 is in the metastable range for oxalate. Values greater than these indicate progressively greater risk of spontaneous crystal formation and growth. Calculating the APR is a much more laborious process than RSS and so is less commonly performed, although it is regarded as a more accurate measure. Clinical management of feline struvite and oxalate urolithiasis Urolithiasis occurs more commonly in sedentary, overweight, middle-aged and older adult cats, with a slightly older mean age for cats affected by oxalate (7.5 years) than struvite uroliths (6.8 years). Studies also suggest that oxalate uroliths are more common in male cats whereas struvite are more common in females. Certain breeds have been identified as being predisposed to oxalate (e.g. British Shorthair, Persian, Burmese), struvite (e.g. Oriental Shorthair), or both (e.g. Himalayan, Foreign Shorthair). Additionally, hypercalcaemia and hypercalciuria have been identified as risk factors for oxalate stones. increased salt content (such as PURINA VETERINARY DIETS Feline UR ST/OX) will encourage a more appropriate water intake, urine volume and urine concentration. Calculating the APR is a much more laborious process than RSS and so is less commonly performed, although it is regarded as a more accurate measure. Struvite The urine ph is known to be a factor that markedly affects the solubility of struvite crystals. A diet designed to both reduce the concentration of the crystalloid precursors of struvite and also produce mildly acidic urine (a ph of 6.0 6.3) such as PURINA VETERINARY DIETS Feline UR ST/OX can produce a low RSS/APR in the undersaturated range (<1) and thus achieve both dissolution of existing stones as well as prevent stone recurrence. The clinician and owner thus have the option of medical dissolution of struvite stones (with regular radiographic monitoring to check progress is appropriate) or surgical removal followed by dietary prevention. When struvite uroliths are identified it is important to also check for urease-producing bacterial urinary tract infections, although these are very much less common in cats than dogs. Similar to oxalate uroliths, maximising water intake will also assist in management and prevention. Prevention of recurrence of struvite urethral plugs follows exactly the same principles, along with consideration of whether there is also underlying idiopathic cystitis. For cats with both struvite and oxalate uroliths, it is important to Maintain optimum body condition and avoid excess weight and obesity Encourage exercise Encourage drinking Encourage frequent urination through the use of multiple clean litter trays using the cat s preferred litter substrate Preventing problems in healthy cats Although there is probably only a subset of cats that are at risk of developing urolithiasis, it is important that known risk factors for development of this disease are minimised. This should include avoiding obesity and excess weight in any cat this clearly has health benefits beyond urolithiasis but will help avoid a sedentary lifestyle and overconsumption of nutrients (including minerals). Encouraging exercise, provision of adequate clean litter trays and providing good sources of fresh drinking water are equally important for all cats. Calcium oxalate Because the rate of dissolution of oxalate stones is so low, even in undersaturated urine, surgical removal of these is required for initial therapy. Following this the use of a diet that produces a low RSS/APR (below the supersaturated range) is indicated to help prevent recurrence such as PURINA VETERINARY DIETS Feline UR ST/OX. Solubility of calcium oxalate crystals is affected very little by urine ph, but urine volume (and thus concentration) and frequency of urination are likely to be important factors in long-term management. The use of a wet (tinned) diet, and encouraging the cat to drink through provision of flavoured waters or water fountains may all be of benefit. For cats that have a strong preference for dry food and cannot be transitioned to a wet diet, a dry diet that contains a moderately 4 Nestlé PURINA Urolithiasis in cats managing the risks 5
Further readings 1. Bartges JW, Kirk CA. Nutrition and lower Urinary tract disease in cats. Vet Clin North Am: Small Anim Pract 2006; 3: 1361-76. 2. Hostutler RA, Chew DJ, DiBartola SP. Recent concepts in Feline Lower Urinary tract disease. Vet Clin North Am: Small Anim Pract 2005; 35: 147-70. 3. Smith BHE, Stevenson AE, Markwell PJ. Urinary relative super saturations of calcium oxalate and struvite in cats are influenced by diet. J Nutr 1998; 128:2763S 4S. 4. Stevenson AE, Wrigglesworth DJ, Markwell PJ. Urine ph and Urinary relative supersaturation in healthy adult cats. In: Rodgers AL, Hibbert BE, Hess B, Khan SR, Preminger GM, editors. Urolithiasis 2000: IX International Symposium on Urolithiasis; 2000 Feb 15 17; Cape Town, South Africa. University of Cape Town: Rondebosch; 2000. p. 818 20. 5. Lulich JP, Osborne CA, Lekcharoensuk C, Kirk CA, Bartges JW. Effects of diet on urine composition of cats with calcium oxalate urolithiasis. J Am Anim Hosp Assoc 2004 May Jun;40:185 91. 6. Bartges JW, Osborne CA, Lulich JP, et al. Methods for evaluating treatment of uroliths. Vet Clin North Am: Small Anim Pract 1999; 29:45. 7. Xu H, Laflamme DP, Bartges JW, Long GL. 2006. Effect of dietary sodium on urine characteristics in healthy adult cats. Journal of Veterinary Internal Medicine (May/June). 738-739. 8. Xu H, Laflamme DP, Riboud C, Long GL. 2007. High sodium diet has no adverse effects on blood pressure or renal function in healthy cats. Journal of Veterinary Internal Medicine (May/June). 601. 6 Nestlé PURINA Urolithiasis in cats managing the risks
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