Management of refractory inflammatory feline lower urinary tract disease (Proceedings)

Key Points

• Sterile, inflammatory cystitis in cats may be caused by multiple factors, including viral or other inflammatory triggers, urothelial defects, neurohormonal aberrations, and environmental stresses.

• The disorder is characterized by occasional episodes of hematuria, pollakiuria, and inappropriate urination that are not associated with bacterial infection and are self-limiting in nature.

• Some cats have more refractory disease, with signs that recur multiple times during a given year or, less commonly, persist for longer than 7 days.

• Treatments that minimize inflammation, protect the urothelium, or modify neurohormonal or behavioral influences can be useful in decreasing the frequency of recurrence in refractory cats.

Etiopathogenesis

By definition, an idiopathic disorder defies clear identification of an etiology. Because of the hematuria and irritative lower urinary symptoms, multiple investigators have searched for an infectious etiology. Common bacterial organisms, however, have not been found in most young cats with this disorder. Viral particles found in some cats, and the episodic nature of the disorder, introduced the possibility of an viral etiology. However, a clear viral causation has not be demonstrated either. Without a clear infectious cause, other epidemiologic and pathophysiologic factors probably contribute to the disorder, including:

• Patient risk factors include neutering, obesity, sedentary lifestyle, living indoors, living in multi-cat households, eating predominantly dry foods

• Changes in protective layers of the urinary bladder, including increased permeability, urothelial mucosal and submucosal damage, mast cell infiltration, and defects in the glycosaminoglycan layer.

• Abnormal stress reponses and neurogenic perpetuation of inflammatory responses. Exaggerated sensory input from afferent neurons in the urinary bladder may trigger inflammatory and pain responses.

• Latent herpesvirus or calicivirus infection may play a role in individual cats.

Diagnostic Evaluation for Recurrent Non-obstructive Feline Idiopathic Cystitis

Many different etiologies can lead to lower urinary tract signs in cats. Although idiopathic cystitis is one of the most common causes of these signs, and can recur in an individual cat, it is important to do a thorough evaluation for other etiologies as well, especially urolithiasis in any cat, and bacterial urinary tract infections in cats with perineal urethrostomies or those undergoing recent urinary catheterization. In recurrent cases, a complete minimum data base and additional anatomical investigation are recommended.

Presentations and diagnostic plans

Practical Management Strategies for Recurrent Non-obstructive Feline Idiopathic Cystitis

Short-term relief can be used for 2 to 5 days during acute flare-ups to minimize discomfort and shorten the hematuric phase.

• Opioids. For acute flare-ups of lower urinary tract signs, short-term analgesic treatments may be useful to reduce the discomfort associated with bladder and urethral inflammation. Butorphanol (0.5 – 1.25 mg/cat PO q 4 – 6 hrs) has been recommended; longer acting buprenorphine can be considered as well. Both agents can be given as subcutaneous injections if less stressful to the cat. Opioids also have some anti-inflammatory effects that may be beneficial in this setting.

• Anti-spasmodics. Agents that relax smooth or striated muscle of the urinary tract have been advocated for symptomatic relief of pollakiuria, dysuria, and stranguria in cats with FLUTD. The anticholinergic agents propantheline and oxybutynin have been recommended for their antispasmodic effects on the urinary bladder. In one small controlled study, propantheline administration did not affect resolution of clinical signs at 5 days post-treatment when compared with placebo; however, this agent has little direct smooth muscle relaxant properties. If urinary bladder antispasmodic agents are administered, cats should be monitored for urine retention; the loss of a frequent mechanical washout of urine theoretically could delay resolution of inflammation or predispose cats to urinary tract infection.

• Alpha adrenergic antagonism. Agents acting on urethral musculature also have been recommended to facilitate urination in dysuric cats and to alleviate functional urethral obstruction in postobstructed cats. Phenoxybenzamine and prazosin are alpha-adrenergic antagonists that inhibit urethral smooth muscle contracture. These agents may be helpful in minimizing resistance in the preprostatic and prostatic portions of the urethra in cats. Diazepam or dantrolene may be more effective in relaxing skeletal muscle in the postprostatic urethra where much of the spasm occurs. Hypotension and sedation are the most common adverse effects of alpha antagonists.

• Glucocorticoid anti-inflammatory agents. Anti-inflammatory effects of glucocorticoids on leukocyte migration, vascular permeability, and arachidonic acid metabolism would be expected to suppress the inflammatory symptomatology and hematuria associated with idiopathic cystitis. However, it appears that glucocorticoids do little to alter the short-term course of typical idiopathic lower urinary tract in placebo-controlled trials. Glucocorticoid administration also is not without risk. Refractory urinary tract infection and pyelonephritis may develop, especially when glucocorticoids are administered to cats with indwelling urinary catheters.

Table. Pharmacologic agents that may be useful in the management of recurrent idiopathic feline cystitis.

• Non-steroidal anti-inflammatory agents. Nonsteroidal anti-inflammatory agents have also been recommended for analgesic and anti-inflammatory effects. No controlled studies are available to demonstrate a response from any of these agents.

Long term strategies are employed for frequently recurrent, idiopathic cases after a thorough diagnostic evaluation. Dietary and environmental strategies are usually employed first. Pharmacologic agents may be added if the cat still experiences frequent recurrences. The effects of treatment may take weeks to months to be fully realized; treatment is indefinite to lifelong.

• Dietary management. High moisture content is probably the primary key to management of recurrent idiopathic cystitis. Moisture can be provided in wet food, fresh water bowls or fountains, or by adding extra water to food. For cats with urethral plugs or struvite crystalluria, canned diets designed to minimize urolith formation are recommended. Owners should strive to minimize frequent changes in diet, as this may trigger episodes.

• Environmental modifications and enhancements. Modification of environment and attention to behavioral issues must be done concurrently to minimize the neuroendocrine influences on the disease. Environmental enrichment, reduction in intra-cat conflict or aggression, feeding method and litter box management are included in the potential modifications.

• Feline pheromones. In a recent prospective clinical trial involving 12 cats, feline facial pheromone was compared to a placebo as treatment for iFLUTD. Although there was no statistical difference between the two groups, more of the pheromone treated cats had less severe and fewer episodes of iFLUTD and further studies are warranted.

• Anti-anxiety medication. Amitriptyline has been studied for both acute non-obstructive episodes and for longer term usage. This tricyclic antidepressant has anticholinergic, antihistaminic, analgesic and anti-inflammatory effects, and is useful in women with interstitial cystitis. In two controlled trials, short-term administration of amitriptyline did not dramatically reduce the duration or severity of lower urinary tract signs, and may have led to earlier recurrence of clinical episodes. For longer term administration, the drug should be given daily for several months to assess effectiveness. Other tricyclic antidepressants or SSRIs may be useful in cats as well; in the author's experience, clomipramine is better tolerated by cats than amitriptyline. For cats in which amitriptyline is indicated, a starting dosage of 5 mg/cat every 24 hours is empirically recommended; the dose is adjusted to effect a mild calming behavior in the cat, which is usually achieved with dosages of 2.5 to 12.5 mg/cat per day. The dose of clomipramine is approximately 0.5 mg/kg/day. If ineffective, these medications should be slowly tapered instead of withdrawn abruptly.

• Glycosaminoglycans. Pentosan polysulfate (PPS, Elmiron) is a synthetic polysaccharide that augments the protective glycosaminoglycan layer of the urinary bladder. Orally administered PPS has resulted in good long-term responses (>6 to 12 months) in some women with IC and may be effective in reducing clinical episodes in cats with recurrent or chronic idiopathic disease. The currently recommended dosage for cats is 8 mg/kg PO q 12 hours.

• Glucosamine and chondroitin sulfate are the building blocks for formation of glycosaminoglycans. Anecdotally these nutritional supplements have been helpful in some cats with chronic disease. A placebo-controlled trial in cats treated with glucosamine alone, however, had no effect on severity or recurrence of signs during a 6 month period.

References

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