FELINE LOWER URINARY TRACT DISEASE-(FLUTD): DIET OR DRUGS?

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FELINE LOWER URINARY TRACT DISEASE-(FLUTD): DIET OR DRUGS?

Postby guest » Tue Sep 16, 2003 8:49 pm

FELINE LOWER URINARY TRACT DISEASE-(FLUTD): DIET OR DRUGS?

LINDA ROSS, DVM, MS, DIPLOMATE ACVIM (INTERNAL MEDICINE)
Tufts Animal Expo Conference Proceedings
September 1, 2001

The full text of the article is below.

LINDA ROSS, DVM, MS, DIPLOMATE ACVIM (INTERNAL MEDICINE)

FELINE LOWER URINARY TRACT DISEASE-(FLUTD): Diet or Drugs?

Small Animal Nephrology/Urology

Linda Ross, DVM, MS, Diplomate ACVIM (Internal Medicine)

Nephrology/Urology Track

Keywords: feline, urinary tract, diet, antibiotics, management

Feline lower urinary tract disease (FLUTD) remains a frustrating problem for veterinarians. Despite extensive diagnostic workups, approximately 65% of these cats will be found to have idiopathic disease. This percentage that has not changed in the last 30 years despite numerous therapeutic recommendations. Because of the inability to identify the cause of the clinical signs, specific measures to correct and treat the problem are not possible.

Diet

The importance of diet in the treatment and prevention of idiopathic FLUTD hinges upon the theory that crystalluria, especially struvite crystalluria, is the cause of the hematuria, stranguria and urinary obstruction. Although struvite crystals continue to be found in the material forming urethral plugs, a cause and effect relationship has never been established. The fact that the incidence of idiopathic FLUTD has not changed for decades despite reformulation of feline diets that have significantly decreased the incidence of struvite crystalluria also speaks against a causative role.

That said, diet can play a role in true urolithiasis, a specific cause of FLUTD. ("True urolithiasis" is used to refer to macroscopically visible uroliths, as opposed to microscopic crystalluria). The incidence of true urolithiasis in cats seems to be increasing. The most recent data suggests that in cats with lower urinary tract signs, up to 20% may have a urolith within the urinary bladder and/or urethra. Therefore, radiographs and/or other diagnostic imaging may be indicated earlier in the diagnostic plan for cats with hematuria and dysuria than might have been indicated previously.

The incidence of the different types of uroliths has changed significantly in cats over the last 15 years. The incidence of struvite (magnesium ammonium phosphate) uroliths has decreased from approximately 90% to approximately 40-50% of the total. Conversely, the incidence of calcium oxalate uroliths has increased from less than 5% to approximately 50-60% of the total. Part of this difference may be due to the fact that some struvite stones are dissolved by medical therapy, meaning that the stone is not available for analysis. However, it is also clear that there has been a true shift in the percentage of each type of urolith. The reasons for this may be due to the types of diets that have been fed to cats in an attempt to reduce the incidence of struvite crystalluria and struvite urolithiasis. These diets are generally restricted in magnesium, may contain supplemental sodium chloride to increase water consumption and decrease urine concentration, and are formulated to produce acid urine. The amount of acidifying agent in the diet may result in some degree of metabolic acidosis. Excess hydrogen ions are buffered by several different systems within the body, one of which is bone, where hydrogen ions exchange with calcium ions. The excess calcium is then excreted in the urine. Increased amounts of sodium chloride may also promote calcium excretion in the urine. In rats and humans, magnesium is an inhibitor of calcium oxalate crystal formation. This has not been studied specifically in cats. Nevertheless, it appears that diets formulated to prevent magnesium ammonium phosphate crystals may be producing conditions which are conducive to calcium oxalate urolith formation. Calcium oxalate uroliths, as opposed to struvite uroliths, cannot be dissolved medically and will require surgical removal.

It is clear that interactions between different dietary components make formulation of the "perfect" feline diet difficult. For example, a recent study indicated that a high protein diet resulted in lower urinary pH and decreased urinary magnesium excretion, resulting in a lower struvite activity product. However, two other studies have indicated that Tamm-Horsfall glycoprotein is correlated with the development of urolithiasis and the growth of struvite crystals. The relationship between dietary protein and quantity of Tamm-Horsfall glycoproteins is not clear. As has been found in the case of diets formulated to reduce struvite crystalluria, altering diets to prevent one disease may truly be a case of "robbing Peter to pay Paul."

Dietary therapy used to be targeted toward reduction of struvite crystalluria. However, the increasing incidence of calcium oxalate urolithiasis and its potential relationship to diets targeted toward reducing struvite crystals makes that recommendation questionable. It does appear that feeding a dry food diet is a risk factor for the formation of uroliths. It appears that cats that consume dry food diets also consume less water, producing a more concentrated urine. The more concentrated the urine, the more readily minerals can exceed their saturation index and crystallize into uroliths. Therefore, increasing water consumption in cats with FLUTD is probably the single most important therapeutic measure that can be instituted. Feeding a canned food diet that is not excessively acidifying or magnesium depleted is one method to accomplish this. Additional water can be mixed in the food to further increase water intake. Other measures to increase water consumption by the cat include making sure the cat always has access to clean water and finding other liquids the cat likes to drink (the author has had good success with bouillon, which has the added benefit of increasing salt intake). Diuretics can be used; alternatively, some owners are willing to administer SQ fluids to the cat at home. Measuring urine specific gravity can be used to monitor the effectiveness of this therapy, with the goal being to maintain a specific gravity of less than 1.025.

Drugs

Antibiotics

Drug therapy for FLUTD can be divided into two categories; specific therapy for FLUTD with an identifiable cause, and empiric therapy for idiopathic disease. (Note: consult Table I for doses.)

Antibiotics are undoubtedly the most mis-used of all drugs for FLUTD. Informal surveys of veterinary practitioners indicate that greater than 90% routinely administer antibiotics to cats with lower urinary tract signs, whether or not a urinalysis has been performed (and almost all without a urine culture). However, numerous studies have shown that bacterial urinary tract infections are responsible for less than 2% of cases of FLUTD. Administration of antibiotics in this situation is similar to the situation in which antibiotics are given to people with colds ("it gets better in 7 days if you treat it, and a week if you don't"). This antibiotic pressure can and is leading to increasing resistance of bacteria, especially when broad spectrum antibiotics such as the fluoroquinolones are used as first line therapy. Despite this, one study that analyzed f data by age indicated that the incidence of bacterial UTI in older cats (over 10 years of age) is approximately 10%. In addition, cats that have been catheterized (either for urethral obstruction or for radiographic studies) may develop iatrogenic infection. Antibiotics should be reserved for those cats that have a documented UTI by urine culture, or prophylactically for 5 to 7 days following urinary catheterization.

Anti-inflammatory and Analgesic Drugs

Corticosteroids have been suggested for chronic or recurrent cases of idiopathic FLUTD. One clinical study of prednisone vs placebo found no difference in response in cats with a first occurrence of FLUTD. However, the author has found that some cats with chronic signs do respond to corticosteroids. It may be that because of the different causes of FLUTD, some cats are steroid-responsive while others are not.

Non-steroidal anti-inflammatory drugs (NSAIDS) have been suggested to reduce inflammation that might be associated with FLUTD. While none are available in the U.S., two are approved for use in cats in Canada (ketoprofen and tolfenamic acid). There are no studies evaluating the efficacy of these drugs for FLUTD.

Some investigators have recently suggested that idiopathic feline lower urinary tract disease in cats may be a condition similar to interstitial cystitis in people. The latter is a disorder characterized by dysuria, stranguria, increased frequency of urination, and significant pain upon urination. Affected patients are usually female, and are diagnosed based upon characteristic lesions visualized during cystoscopic examination (glomerulations, which are actually submucosal petechial hemorrhages, or small ulcers in the bladder mucosa). These lesions must be multifocal, diffuse, and severe. In addition, the disease in people typically follows a waxing and waning course, and signs tend to flare during stress, similar to FUS in cats. This possibility is currently being investigated, and although it would allow us to categorize the disease better, it does not offer any more therapeutic options because the syndrome in people is also notoriously difficult to treat.

Amitriptyline, a tricyclic anti-depressant, has been suggested as therapy for cats with FIC. Amitriptyline also has anticholinergic, antihistaminic, anti-alpha adrenergic, antiinflammatory, and analgesic properties. Clinical experience suggests that some cats experience relief from clinical signs, although it has been suggested that this is the result of the sedative properties of the drug. A recent study compared amitriptyline to placebo for treatment of cats with idiopathic FLUTD. Cats receiving amitriptyline had a significantly shorter time to resolution of pollakiuria, although no difference in resolution of hematuria. However, cats that received amitriptyline had a shorter time to and more frequent recurrence of clinical signs. A mechanism for this effect was not suggested.

Analgesics have been suggested to relieve pain associated with stranguria. Aa mentioned above, amitriptyline may have some analgesic properties. Butorphanol has also been reported to provide relief in some cases.

The urinary bladder is lined by transitional epithelium, which in turn is lined by a coating of glycosaminoglycan. The latter prevents adherence of bacteria and crystals, and limits the permeability of the epithelium to urine. This layer has been found to be abnormal in women with interstitial cystitis. Pentosan polysulfate (Elmiron) is a synthetic polysaccharide that can mimic or replace the glycosaminoglycan layer, and is available as an oral preparation. If, in fact, idiopathic FLUTD and interstitial cystitis in women are comparable syndromes, therapy with pentosan polysulfate might be beneficial in both. While some studies in women have shown improvement after treatment with pentosan polysulfate, clinical studies in cats (as yet unpublished) have failed to show a similar response. Further multi-center studies are ongoing.

Antispasmodics

Antispasmodics can be divided into two categories; those that act primarily on the smooth muscle of the bladder, and those that act on the urethral sphincter. Propantheline and oxybutynin act on the bladder, and have been suggested to relieve discomfort in those cats with severe stranguria. One study failed to show any benefit when 7.5 mg propantheline was administered orally once; no other controlled studies have been published. Drugs that act on the smooth muscle of the urethral sphincter include phenoxybenzamine and prazosin; those that act on the striated muscle are diazepam and dantrolene. They are used when urethral spasm is believed to be present (e.g., small urine stream in the absence of mechanical obstruction). Phenoxybenzamine is rarely used now due to cost. Prazosin has been shown to be effective in reducing urethral pressure; however, because it also reduces blood pressure it can be associated with weakness, disorientation, and drowsiness. Diazepam can cause idiosyncratic hepatotoxicity; although a rare effect, some clinicians prefer not to use it for this reason. Dantrolene is effective, but must be compounded from the human dose. It can cause generalized muscle weakness and drowsiness, and also can be hepatotoxic.

It is important to remember that the cause of lower urinary tract signs can change. Cats can develop urinary tract infections, especially if the urinary tract has been catheterized; uroliths may develop. Cats with chronic FLUTD should have some diagnostic tests, especially urine culture and abdominal radiography, repeated periodically (q 6-12 months). Identification of a specific cause then allows more appropriate therapy.

Table I



Drugs used in the Management of FLUTD



Drug Class
Drug
Suggested Dosages

Anti-spasmodic - bladder
Propantheline



Oxybutynin
7.5 mg every 72 hours



0.5-1.25 mg PO q 8-12 hrs

Anti-spasmodic - urethra

Smooth muscle


Phenoxybenzamine



Prazosin


2.5 mg PO q 8-12 hrs



0.25 mg PO q 12-24 hrs

Striated muscle
Diazepam



Dantrolene
0.22 mg/kg PO q 8-12 hrs



0.5-2 mg/kg PO q 8-12 hrs

Anti-inflammatory,

analgesic
Amitriptyline



Prednisone
5-10 mg/cat/day



2.2 mg/kg q 24 hrs, taper dose

Butorphanol

(Torbugesic)
0.3 mg/kg q 8-12 hrs

for 2-4 days

Miscellaneous
Pentosan polysulfate

sodium (Elmiron)
8 mg/kg q 12 hrs or

25-33 mg/cat q 12 hrs




References and Suggested Reading

Dowling PM: Potential therapies for recurrent idiopathic cystitis in cats. Vet Med 95:512-515, 2000.

Kruger JM, Kalkstein T, Kaneene JB, et al: Clinical trial of amitriptyline for management of acute nonobstructive feline idiopathic urinary tract disease [abstract]. J Vet Int Med 15:303, 2001.

Lane IF, Barges JW: Treating refractory idiopathic lower urinary tract disease in cats. Vet Med 94:633-641, 1999.

Markwell PF, Buffington CT, Smith BH: The effect of diet on lower urinary tract diseases in cats. J Nutr 128[12 Suppl]:2753S-2757S, 1998.

Smith BHE, Moodie S, Markwell PJ: Long-term feeding of an acidifying diet to cats: Effect on bone density [abstract]. J Vet Int Med 15:305, 2001.
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