Nutrition and Urinary Tract Disease—Myths and Legends

Nutrition is an important component to patient care and dietary modification is indicated for many diseases of the urinary tract. While some recommendations are supported by scientific evidence, some are not. Oftentimes, these recommendations are based on unsupported theory or extrapolated information from experimental models or other species.

Salt and Urinary Tract Disease

Clinical signs improve significantly in human beings, cats, and dogs with lower urinary tract disease, particularly urolithiasis, when water intake and urine volume are increased.^1,2 Short term feeding studies demonstrate increased levels of sodium chloride fed to cats in dry foods significantly increases water intake, urine output, and urine dilution without an increase in blood pressure or an impact on overall health.^3–5 These studies also found decreased urinary saturation for calcium oxalate due to increased urine volume. In some human beings, high salt intake may be associated with systemic arterial hypertension. In dogs and cats, systemic arterial hypertension is associated with renal disease, endocrine abnormalities, and obesity, but studies have failed to document increased blood pressure with increased salt intake.^5,6 High salt intake, however, may be deleterious without affecting blood pressure. ⁷

Studies in healthy dogs and cats, have shown that high salt intake is associated with increased urine volume and decreased urinary saturation for calcium oxalate.^8,9 In other studies, high salt intake did not adversely affect blood pressure in healthy animals or animals with renal failure.^5,6 These studies evaluated healthy animals, animals with induced disease, or were of short duration. In a longer term study of cats that were healthy, were obese, were older, or had renal insufficiency, high dietary salt increased water intake and urine output in cats except for those with renal insufficiency. ¹⁰ It was not associated with increased blood pressure in any group; however, it was associated with increased serum concentrations of urea nitrogen, creatinine, and phosphorous in all cats with the greatest increase in cats with renal insufficiency. Sodium restriction in cats with renal insufficiency must be done cautiously, however, as low salt intake was associated with hypokalemia in a group of cats with experimentally-induced renal insufficiency. ⁶

Thus, salt supplementation and salt restriction must be done cautiously and patients should be monitored. Increased dietary sodium may increase urinary calcium excretion and can contribute to ongoing renal damage in cats with marginal renal function.

Diet and Nutraceuticals for Feline Idiopathic Cystitis

Feline idiopathic cystitis is a common, yet frustrating cause of lower urinary tract signs in cats. The cause(s) is/are not known, and the biological behavior is unpredictable. Many cats experience self-limiting clinical signs, and recurrence rate is variable. Because of this, treatments often appear effective in an individual cat; however, results are disappointing in controlled clinical trials. There are several hypotheses as the cause(s) of idiopathic cystitis. One study documented decreased glycosaminoglycan excretion in cats with idiopathic cystitis regardless of whether clinical signs were present or not. ¹¹ This finding is similar to those in women with interstitial cystitis. Decreased urinary glycosaminoglycan levels may represent decreased glycosaminoglycans at the uroepithelial surface, which, in turn, may be associated with increased permeability. ¹² Some women with interstitial cystitis respond to systemic or intravesicular glycosaminoglycan treatment.^13–15 To date, only 1 controlled study evaluating N-acetylglucosamine administration to cats with idiopathic cystitis has been published; it was found no more effective than placebo. ¹⁶ Similar results were found in an unpublished controlled study of pentosan polysulfated sodium in cats. No other glycosaminoglycans have been evaluated for management of feline idiopathic cystitis.

A current recommendation for managing cats with idiopathic cystitis is feeding a canned diet. This recommendation is based on the results of clinical study comparing recurrence rates of clinical signs in cats fed either a canned or dry food over a 12-month period. ² In this study, recurrence of clinical signs occurred in 11% of cats fed a canned food compared with 39% of cats fed a dry food. Problems with this study included lack of randomization to diet fed and drop-out of more cats in the canned food group than in the dry food group. In another study evaluating N-acetyl glucosamine treatment for feline idiopathic cystitis, improvement in clinical signs and decreased recurrence was attributed to owners feeding a canned diet rather than to the glucosamine. ¹⁶

Based on the results of these studies, it seems logical to try dietary therapy utilizing a canned food in cats with recurrent idiopathic cystitis, if possible. This may decrease clinical signs, decrease recurrence, and prevent or delay use of pharmacological treatment in some cats.

Diet and Infection-Induced Struvite Uroliths

Struvite stone formation can occur as a consequence of an infection with a urease-producing microbial organism (infection-induced struvite) or without a microbial infection (sterile struvite). Dietary modification to prevent sterile struvite recurrence appears to be important; however, the role of diet in prevention of infection-induced struvite stones is less clear. There are several diets formulated and marketed for prevention of infection-induced struvite stones. These diets are designed to decrease urinary excretion of magnesium, ammonium, and phosphate and to induce aciduria in order to decrease urinary saturation for struvite and thus to decrease risk of recurrence.

There are several points to consider. Struvite crystalluria occurs commonly in healthy dogs, and without a microbial infection, struvite stones do not form. ¹⁷ Although sterile struvite urolith formation has been described in dogs ¹⁸ , most struvite stones are infection-induced. ¹⁹ In this situation, it is the infection that causes the struvite uroliths to form due to the activity of microbial urease in the urine. When urinary tract infection with urease-producing microbes occurs in animals forming urine with a sufficient quantity of urea, the unique combination of concomitant elevation in the concentrations of ammonium and carbonate in an alkaline environment may develop. These conditions favor formation of uroliths containing struvite, calcium apatite, and carbonate apatite. The following mechanisms are involved: 1) Urease (a metalloenzyme containing nickel) produced by bacteria or ureaplasma hydrolyzes urea to form two molecules of ammonia and a molecule of carbon dioxide. 2) The ammonia molecules react spontaneously with water to form ammonium and hydroxyl ions (pK of NH3 = 9.03), which alkalinizes urine by reducing hydrogen ion concentration. The solubility of struvite and calcium apatite decreases in alkaline urine.

Most bacteria can survive and grow over a range of 3 pH units, about a thousand-fold change in [H+]. The range of pH over which an organism grows is defined by three cardinal paints: the minimum pH, below which the organism cannot grow, the maximum pH, above which the organism cannot grow, and the optimum pH, at which the organism grows best. For most bacteria there is an orderly increase in growth rate between the minimum and the optimum and a corresponding orderly decrease in growth rate between the optimum and the maximum pH, reflecting the general effect of changing [H+] on the rates of enzymatic reaction. Escherichia coliis the most common organism causing urinary tract infections in dogs and cats, but does not produce urease; it has a minimum pH of 4.4, optimum pH of 6.0-7.0, and a maximum pH of 9.0. Staphylococcus spp are the most common cause of infection-induced struvite urolith formation; they have a minimum pH of 4.2, optimum pH of 7.0-7.5, and a maximum pH = 9.3. Dogs and cats cannot acidify their urine to less than 5.0-5.518, an it can not be more basic than 9.0; therefore, it is not possible to acidify the urine of a dog or cat to prevent a microbial urinary tract infection.

Dietary modification for prevention of infection-induced struvite uroliths is not warranted based on this information. For prevention of infection-induced struvite uroliths, control of urinary tract infections with urease-producing microbes is effective, regardless of diet. Feeding an acidifying diet or administering an acidifying agent is not effective in prevention of microbial infections and would, therefore, not be effective in preventing infection-induced struvite urolith formation.

Urinary Saturation Studies

Formation of uroliths is not a disease, but rather a complication of several disorders. ²⁰ Some disorders can be identified and corrected (such as infection-induced struvite urolith formation), some can be identified but not corrected (such as hyperuricosuria that occurs in Dalmatians that form ammonium urate uroliths), while for others the underlying etiopathogenesis is not known (such as calcium oxalate urolith formation in Miniature Schnauzers). A common denominator of these disorders is that they can from time to time create oversaturation of urine with one or more crystal precursors resulting in formation of crystals. Urolith formation, dissolution, and prevention involve complex physical processes. Major factors include: 1) supersaturation resulting in crystal formation, 2) effects of inhibitors of crystallization and inhibitors of crystal aggregation and growth, 3) crystalloid complexors, 4) effects of promoters of crystal aggregation and growth, and 5) effects of noncrystalline matrix. ²¹

Because supersaturation of urine with stone-forming substances is necessary for stones to form, measurement of urine saturation with minerals is a more accurate means of assessing risk of stone formation. There are 2 basic techniques for estimating urinary saturation. One technique uses untreated urine and the second technique uses seed crystals of the calculogenic minerals of interest. Each general technique has its advantages and disadvantages. The most common technique using untreated urine is estimation of the relative supersaturation. The advantage is that biochemical measurements are done one time and results are entered into a computer program, EQUIL or SUPERSAT, that estimates the relative supersaturation.^21–23 Disadvantages of this technique include discrepancy in results between the computer programs especially for struvite, and the fact that unmeasured compounds and inhibitors are not accounted for. The second technique uses seed crystals of the calculogenic minerals of interest. Biochemical measurements are done on urine before and after incubation with the seed crystals, and results are entered into a computer program that estimates the activity product in both samples. An activity product ratio is calculated by dividing the activity product of the urine before incubation by the activity product of the urine after incubation with seed crystals. Advantage of seed crystal techniques is that they incorporate unmeasured compounds including inhibitors because the patient's urine is used before and after seed crystal incubation. Disadvantages include cost and the fact that these techniques overestimate undersaturation, underestimate supersaturation, and correctly estimate saturation, provided that a sufficient amount of seed crystals have been used. Both techniques have been used experimentally in dogs and cats^24–27, and have been used to develop diets for managing crystalluria and urolithiasis; however, most studies have used healthy animals and not animals that are stone formers. One study showed decreased urinary saturation using activity product ratios for calcium oxalate in a group of cats that had formed calcium oxalate uroliths when they were fed an “oxalate preventative” diet compared with the diet on which they formed the uroliths. ²⁸ A study in dogs showed higher relative supersaturation values for calcium oxalate in dogs that had formed calcium oxalate stones when compared with non-stone forming dogs. ²⁶ Relative supersaturation values have shown that older cats are at greater risk of forming calcium oxalate than younger cats. ²⁹ However, there are no studies that have correlated estimates of urinary saturation with urolith recurrence rates in dogs or cats that have formed uroliths.

Currently there are several diets marketed as preventative for struvite and calcium oxalate in dogs and cats. Because struvite uroliths almost always form due to a urease-producing microbial infection in dogs, such diets are not likely to be of benefit as discussed previously. In cats, struvite uroliths typically form without a microbial infection. The “combination preventative” diets for cats are based on estimation of urinary saturation for calcium oxalate and struvite in healthy cats, and not in cats that have formed either type of urolith. It is interesting to note that based on previously published epidemiological studies and current estimates of cats in the United States, more than 99% of cats do not form uroliths regardless of diet. The role of diet in preventing urolith recurrence in urolith-forming patients in long term clinical trials has not yet been determined.