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A highly palatable chewable nutritional supplement for the support of urinary tract health in dogs and cats. Manufactured exclusively for PRN Pharmacal, CranVet contains ten times higher levels of phenols than other natural products. The patented process used to formulate the cranberry extract also eliminates unwanted sugars and oxalic acid resulting in a product that meets the needs of animals with diabetes mellitus. And CranVet does not interfere with the veterinarian’s choice of antibiotics.

UTI – A Common Problem: Urinary tract infections (UTI) are very common in dogs. An estimated 14% of dogs in the United States develop UTI at least once in their lifetime. Three percent to 9% of all dogs seen at veterinary teaching hospitals have UTI. Less common in cats (1% to 3% incidence), UTI generally occurs in cats older than 10 years.

Asymptomatic infections are common in both dogs and cats, especially animals with diabetes mellitus, hyperadrenalcorticism or on glucocorticoids. UTI was diagnosed by in vivo culture in 37% of dogs with diabetes mellitus and 46% with hyperadrenalcorticism in a 2002 study. Eighteen percent of dogs with pruritic disorders receiving long-term treatment with glycocorticoids also had UTI¹.

UTI is usually caused by bacteria: E. coli accounts for 37% to 67% of isolated uropathogens in dogs². A study at the University of Georgia shows that 75% of the pathogens were gram negative, including E. coli, Proteus, Klebsiella, Pseudomonas³. Persistent and reoccurring E. coli UTI in dogs is a frustrating clinical problem⁴.

	Lower Urinary Tract	Upper Urinary Tract
Clinical Signs	Dysuria Stranguria Pollakiuria Hematuria	Signs of renal failure Anorexia, depression Fever Polyuria polydipsia
Physical Examination	Bladder palpation may be painful	Pyrexia, depression Renal pain
Hematology	Normal	Leukocytosis if acute
Blood Clarity	Normal	Normal to increased BUN creatinine
Urine Analysis	Pyuria Hematuria Proteinuria Bacteriuria urine (culture)	Urine specific gravity mey be low Pyriua, Hematuria Proteniuria Urine culture
Radiology	No significant findings	Requires intravenous urography or ultrasonography for diagnosis

The majority of P-fimbriae E. coli that cause UTI bind glycosphingolipid receptor sites i.e. α Gal (1 to 4 β Gal disaccharide) on the uro-epithelial cells that are similar to the P blood group antigens on the surface red blood cells⁵.Furthermore, canine UTI pathogens may pose an infectious threat to humans⁶. Careful selection of antibiotics remains the treatment of choice for clinical cases. However, since recurrences occur frequently in dogs, complementary use of cranberry extracts should be considered by the clinician.

Bladder epithelial cells with E. coli attached.

E.coli via a specific adhesion to a receptor on the host cell membrane.

The Pathology: Bacteria present in the urinary tract first attaches to the epithelial surface of the urinary tract. Uropathogenic strains of E.coli possess Type-I and P fimbriae. Fimbriae are proteinaceous molecules that facilitate the adhesion to uroepithelial cells. The mechanism of bacterial pathogenicity is summarized on the illustration below.


American Cranberry – It’s a Natural: Vaccinium macrocarpon, the American cranberry, is one of only three species of fruits native to North America. Cranberry is a traditional medicine used by Native Americans for the treatment of bladder and kidney ailments for centuries. Interest in the composition of cranberry has been intensified because of the increased awareness of their possible positive health effects. Berries are a rich source of bioactive compounds, including fiber, vitamins, minerals, various phenolic compounds and citric, malic, quinic and glucoronic organic acids. The chemical structure of the main classes of phenolic compounds in berries is summarized in Figure 1 below ⁷.

Figure 1: The chemical structure of phenolic compounds in berries.

Most of the benefits available from cranberries are derived from the unique structure of natural tannins called proanthocyanidins or PACs. Cranberry PACs contain an unusual A-type linkage different from the more common B-type linkage found in proanthocyanidins from other foods. Two compounds in cranberry juice have been shown to inhibit the adherence of E. coli to uroepithelial cells. Fructose, common to many fruit juices, has been implicated in inhibiting adherence of Type I-fimbriated E. coli; the second, proanthocyanidin, is responsible for inhibiting adherence of the Type P-fimbriated E. coli fimbriae⁸.

Experiments with mice have suggested that a bioactive pro-anthocyanidin metabolite inhibits bacterial adhesion in the urinary tract⁹. The A-type proanthocyanidins from cranberries elicited in vitro anti-adhesion activity at 60 μg/ml. In contrast, the B-type pro- anthocyanidins from grape juice exhibited only minor activity at 1200 μg/ml while B-type proanthocyanidins found in apple juice, green tea and dark chocolate were not active¹⁰.

The biological role of bacterial fimbriae is to act as adhesions between the bacteria and receptors on mammalian cells. Cranberry extracts on P-fimbriated E. coli11 inhibit this activity two ways:

• There is a conformational change in the surface fimbriae indicating the proteins are becoming more compressed on the bacterial surface when cranberry is present.
• Cranberry extracts interfere with the adhesive action of P-fimbriae causing a decrease in the adhesion forces between the cell surface and the bacterium.

The CranVet Difference: Typically cranberry extracts contain 3% phenols. CranVet is made from a unique patented process which extracts ten times higher levels of phenols than other natural products. This process generates levels of phenolic compounds of 30%, resulting in a product that has greater potency and enhanced urinary tract support. An additional benefit, especially for animals diagnosed with diabetes mellitus, CranVet contains no sugar or other unwanted molecules such as oxalic acid.

Phenolic compounds 3% Other Cranberry Extracts

Phenolic compounds including Proanthocyanidins and other antioxidants 30% CranVet

	For use in dogs and cats. Helps support the healthy function of the urinary tract.   For those prone to infection of the urogenital system with recurrent UTI. One tablet per 20 kg of body weight, 1⁄2 tablet per 10 kg of body weight. Use 2 tablets per 20 kg of body weight during UTI occurrence (split morning and evening). Calcium Phosphate, Microcrystalline, Cellulose, Whey, Sucrose, Liver Powder, Hydrolyzed Vegetable Protein, Stearic Acid, Silicon Dioxide, Iron Oxide and Magnesium Stearate Store at room temperature 15°-30°C (58°-86°F)

¹ Torres et al, November, 2005, FEM Journal Volume 252 Issue 2 pp. 183
² Ling, G.V. et al., 1979, Veterinary Clinician North America (Small Animal Practice), 9, pp. 617-630; Kiristo et al., 1977, Journal of Small Animal Practitioners, 18, pp. 707-712.
³ Finco, D.R., 1980 in Kirk, R.W. (ed) Current Veterinary Therapy VII, Philadelphia, W.B Saunders Co., pp. 1158-1161.
⁴ 2005Drazenovich, N. et al., 2004, Journal of Veterinary Internal Medicine, 18, pp. 301-306; Polzin, D. J., 2006, Compendium Continuing Education Practicing Veterinarians, 28, Supplement, pp. 7-15.
⁵ Foo, L.Y. et al., 2000, Phytochemistry, 54, pp. 173-181.
⁶ Johnson, J.R., 2001, Journal of Infectious Disease, 182, pp. 897-906.
⁷ Puupponen-Pima, R., 2005, Applied Microbial Biotechnology, 67, pp. 8-18.