In cats, the majority of uroliths found in the bladder are composed of magnesium ammonium phosphate (struvite) or calcium oxalate(Reference Osborne, Lulich, Kruger, Osborne and Lulich1–Reference Houston and Moore3). Surveys on the prevalence of struvite and calcium oxalate uroliths in stone laboratories worldwide indicate that the occurrence of those two stones represents approximately 95 % of submissions. Struvite and calcium oxalate are more or less equally represented, with a slight advantage to one of them depending on the country(Reference Osborne, Lulich, Kruger, Osborne and Lulich1–Reference Houston, Moore and Favrin8).
The most important risk factors for struvite formation are urinary pH and urine dilution, which will affect the concentrations of magnesium, ammonium and phosphate(Reference Lekcharoensuk, Osborne and Lulich4). Contributing factors to struvite uroliths in cats may include periods of inclement weather in which cats tend to remain indoors for prolonged periods of time, inactivity, and feeding of low moisture, non-acidifying dry cat foods(Reference Jones, Sanson and Morris9). In a retrospective case–control study, diets with high Mg, P, Ca, Cl and fibre, moderate protein and low fat content were associated with increased risk(Reference Lekcharoensuk, Osborne and Lulich10).
Previous studies have shown the efficacy of canned(Reference Osborne, Lulich and Kruger11, Reference Houston, Rinkardt and Hilton12) and dry(Reference Houston, Rinkardt and Hilton12) urine-acidifying diets in dissolving feline struvite stones. A study in our laboratory has found that the urine of healthy cats fed a dry-extruded diet, formulated to generate a urinary struvite relative supersaturation (RSS) < 1, dissolved feline struvite uroliths in vitro (Reference van Hoek, Malandain and Tournier13). Therefore, the present study was undertaken to confirm that diets inducing struvite RSS < 1 and effective in dissolving struvite stones in vitro were also effective in dissolving naturally occurring struvite stones in vivo.
Materials and methods
Cats were recruited from veterinary hospitals across Canada. They entered the study on the basis of clinical signs of lower urinary tract disease including, but not limited to, haematuria, stranguria, pollakiuria, inappropriate urination and radiographic evidence of radiodense uroliths. Parameters at inclusion included a complete blood cell count, serum biochemistry, urinalysis, aerobic urine culture and survey abdominal radiographs by the local veterinarian. The presence of struvite crystals was not necessary for inclusion. Urine culture and sensitivity were performed on all cats. Attending veterinarians were requested to perform cystocentesis and administer antibiotics based on culture and sensitivity results. Exclusion criteria included the presence of significant disease such as renal failure, presence of uroliths in the ureters or urethra, and evidence suggesting that the stones may be composed of other mineral types. Radiographs and urinalysis were repeated on a weekly basis and evaluated by two board-certified internal medicine specialists (D. M. H. and M. D. E.) to assess time of complete stone dissolution.
All cats in the present study were client-owned. The cats were maintained in their home environments and the attending veterinarian was responsible for case management. The owners were instructed to feed either the wet (Feline Veterinary diet, Urinary S/O; Royal Canin, Aimargues, France) or dry test diet (Feline Veterinary diet, Urinary S/O in North America and Urinary High Dilution in other areas of the World, Royal Canin, Aimargues, France) exclusively for the duration of the trial. No combination of the wet and dry diets was allowed. The owner determined which form of diet to feed their cat based on prior preferences. Key diet parameters are listed in Table 1.
Key parameters of the diet (dry or wet) fed
RSS, relative supersaturation; MAP, magnesium ammonium phosphate; ME, metabolisable energy.
* Veterinary Diet Urinary S/O, Guelph, Ontario, Canada, Urinary High Dilution (rest of the world), Royal Canin, Aimargues, France.
† Veterinary diet Urinary S/O wet, Royal Canin, Aimargues, France.
‡ ME was measured by animal trials according to the American Association of Feed Control Officials protocol (2010).
If stones failed to dissolve within 12 weeks, surgery was performed and uroliths were analysed quantitatively at the Canadian Veterinary Urolith Centre (Guelph, ON, Canada). The study was reviewed and approved by the Ethics Committee of Royal Canin and owners gave informed consent for inclusion.
Data are expressed as medians and ranges. Results were analysed for effects of diet, sex and urine culture on time to dissolution using a Mann–Whitney U test. These analyses were performed using an open statistical software (TANAGRA: TANGRA, Ricco Rakotomalala, Lyon, France, 2004, http://eric.univ-lyon2.fr/~ricco/tanagra/).
Results
A total of twenty-one cats were used in the present study. Complete stone dissolution was observed in seventeen cats including thirteen spayed female and four neutered male cats. Stones in four cats failed to show radiographic change and were surgically removed. Quantitative analysis confirmed three of those stones to be calcium oxalate and one to be calcium phosphate.
Of the seventeen cats with complete dissolution, eight were fed the wet and nine the dry test diets, respectively. The median age was 5·5 (range 2–15) years (Table 2) and body weights 6·0 (range 3·5–11·8) kg. Struvite stones dissolved in a median time of 19 (10–42) d and 16 (14–55) d in cats fed dry or wet diet, respectively (Table 2). No significant effect of sex (P = 0·4993) and form of diet (P = 0·8845) on time of dissolution was found.
(Medians and ranges)
* Of the six cats with positive urine cultures, two cats had Staphylococcus intermedius, one had Escherichia coli, one had Enterococcus, one had Klebsiella, and one had S. intermedius and E. coli. The time to dissolution between cats with a positive culture v. those with a negative culture was not significant.
It was found that six cats (35 %) had positive urine cultures. The median time to dissolution of uroliths in these cats was 21·5 (range 13–48) d compared with 15 (range 10–55) d for the negative cats; this difference was not significant (P = 0·4790; Table 2).
Discussion
High urine pH (>6·5) and concentrated urine are risk factors for struvite crystal and stone formation(Reference Robertson, Jones and Heaton14). Over the past 10 years, urine RSS has been used to evaluate the ability of diets to generate an undersaturated urine (RSS < 1) and thus their ability to prevent and dissolve struvite stones(Reference Robertson, Jones and Heaton14). We have recently showed in our laboratory that feline struvite uroliths can be dissolved in vitro using urine from cats fed a diet generating a urinary struvite RSS < 1, the dry test diet used in the present study(Reference van Hoek, Malandain and Tournier13). RSS and in vitro studies are easier to perform than clinical trials but the efficacy of those measurements to assess the ability of a diet to dissolve naturally occurring struvite stones remains to be determined. Indeed, stone formers might have different urine composition than healthy controls. It has also been suggested that the presence of inhibitors and promoters of crystal formation and aggregation might be different in affected animals(Reference Osborne, Lulich, Kruger, Osborne and Lulich1). Both test diets used in the present study have been shown to induce in healthy cats a RSS < 1 according to the protocol described by Robertson et al. (Reference Robertson, Jones and Heaton14). Both these diets also induced complete dissolution of radio-dense uroliths in seventeen of the twenty-one cats. In the four cats in which no dissolution was observed, we established that the mineral composition was not struvite. Therefore, the present study strongly suggests that in vitro dissolution and struvite RSS measurements are good surrogate markers of in vivo efficacy. Although on a small number of patients, our data suggest that a well-formulated dry diet is as efficient in dissolving struvite stones as a wet diet.
Females were over-represented in the present dissolution study compared with previous dissolution studies(Reference Osborne, Lulich and Kruger11, Reference Houston, Rinkardt and Hilton12) and reviews on feline urolithiasis(Reference Houston and Moore3, Reference Gerber, Boretti and Lkey5, Reference Westropp, Buffington, Chew, Ettinger and Feldman7). The weight and age of cats used in the present study were similar to those reported previously (Reference Osborne, Lulich, Kruger, Osborne and Lulich1, Reference Houston and Moore3, Reference Gerber, Boretti and Lkey5, Reference Westropp, Buffington, Chew, Ettinger and Feldman7).
In dogs, urinary tract infection is the most common cause of struvite uroliths(Reference Seaman and Bartges15). Urinary tract infection as a cause of struvite uroliths has been reported as rare in cats (around 3 %) except in the very young ( < 1 year) and old ones (>10 years)(Reference Osborne, Lulich, Kruger, Osborne and Lulich1, Reference Osborne, Kruger, Lulich, Ettinger and Feldman16, Reference Lekcharoensuk17). In the present study, 35 % of the cats had positive cultures on samples taken by cystocentesis and only one of those cats was more than 10 years of age. Of the six positive cats, three had urinary tract infections with known urease-splitting bacteria (Staphylococcus intermedius) that promotes alkaline urine as well as struvite crystal and stone formation. Time to dissolution in those three cats (13–48 d) was not different from either the cats with no urea-splitting bacteria (17–28 d) or the cats without bacteriuria (10–55 d). The reason for this high prevalence of bacteriuria remains unclear and, in some cases, might be the result of contamination at the time of sampling or secondary infection due to the presence of the uroliths.
Conclusion
Our data strongly suggest that a diet designed to generate undersaturated urine for struvite (RSS < 1) is effective for both in vivo and in vitro dissolution of struvite bladder stones. Screening diets based on their urine struvite RSS is a rapid and efficient way to assess their efficacy in the prevention and dissolution of naturally occurring struvite uroliths.
Acknowledgements
All authors are employees of Royal Canin and all contributed to the design of the study and preparation of the manuscript. The study was funded by Royal Canin. The authors would like to thank the Veterinary Clinics and their staff who contributed to the inclusion of the cases.
