The frustrations of FLUTD (Proceedings)

Objectives

• Define the various etiologies that fall under the umbrella of FLUTD

• Evaluate recent literature on the possible causes of idiopathic FLUTD

• Discuss the appropriate diagnostic approach to pollakiuria/hematuria/stranguria in the cat

• Outline the rationale behind various therapies and their expected outcomes

Key Points

• FLUTD encompasses all etiologies that result in pollakiuria, hematuria, stranguria, dysuria and periuria in the cat

• Etiologies include: bacterial infection (rare in the cat), urolithiasis, neoplasia, congenital defects and idiopathic FLUTD

• Proposed causes of idiopathic FLUTD have not been consistently supported by epidemiologic or prospective studies

• Regardless of etiology, a thorough workup includes urinalysis, urine culture, CBC, biochemistry panel, radiography and ultrasound or contrast studies

• Treatments for idiopathic FLUTD are based in sound theory, but few have been supported by rigorous, prospective studies

• Recommended therapies include increasing dietary water content, MEMO ± amitriptyline and glucosamine

Background

FLUTD refers to a spectrum of diseases that result in pollakiuria, hematuria, stranguria, dysuria and/or periuria in the cat. Common causes of these clinical signs include urolithiasis, urethral plugs and neoplasia (most commonly, transitional cell carcinoma). Urination in inappropriate places (periuria) may be due to behavioral issues and must be investigated with a thorough history and description of the cat's home environment. Although bacterial infections are common in the canine population, they are an uncommon cause of FLUTD in cats. Feline idiopathic cystitis (FIC) or idiopathic FLUTD (iFLUTD) is characterized by chronic voiding signs (dysuria, hematuria, pollakiuria and/or inappropriate urination), sterile urine with no cytologic abnormalities and evidence of glomerulations (pinpoint submucosal hemorrhages) on cytoscopic examination. It is ultimately a diagnosis of exclusion and is one of the more common causes of lower urinary tract signs (LUTS) in cats < 8 years of age.

Possible etiologies for idiopathic FLUTD

Several etiologies have been suggested for iFLUTD. One hypothesis suggests that alterations of bladder enervation and depletion of the glycosaminoglycan (GAG) protective layer exposes and/or up-regulates of C-pain fibers. This, in turn, results in release of substance P which has multiple effects on the bladder urothelium and may account for a vicious cycle of pain and dysuria. Bacterial infections are extremely uncommon in cats under 10 yrs of age, and given the normal age group of cats presenting with LUTS (young to middle-aged), it is also an unlikely cause of LUTS in this age group. The majority of bacterial infections detected in cats are iatrogenic (catheterization) or secondary to an instigating cause (neoplasia, urolithiasis, congenital defect). Cats older than 10 years have a higher incidence of UTIs, perhaps related to renal insufficiency and decreased urine specific gravity. Some studies have identified Mycoplasma and Ureaplasma in feline urine, but a link to the etiology of iFLUTD has not been established. Another study identified DNA from gram-negative bacteria using PCR from cats with iFLUTD that had negative bacterial culture, suggesting perhaps cell wall deficient bacteria. Bovine herpesvirus-4 has been shown in an experimental setting to induce iFLUTD and BHV-4 has been isolated in some cats with iFLUTD. Likewise, calicivirus-like particles have been detected in cats with urethral plugs. Stress is currently being investigated with interesting results. Catecholamines are elevated in cats and adrenergic receptors in the CNS and within the bladder which normally abrogate the effects of catecholamine are down-regulated. Cats for which environmental stress management techniques have been instituted have fewer episodes of iFLUTD. Despite some supporting evidence for each of these infectious and neurogenic inflammation hypotheses, no single cause has been consistently identified in all cats with iFLUTD.

Working up FLUTD

Keeping in mind that FLUTD is an umbrella of diseases, each cat presenting with stranguria, pollakiuria, inappropriate urination or partial/complete obstruction should be approached similarly. iFLUTD is a diagnosis of exclusion. A typical workup for these cats includes:

Urinalysis

Cystocentesis is preferred, but may be difficult because these cats often have small irritated bladders. Free-catch samples can be helpful for cytologic analysis, but positive cultures obtained from free-catch samples should be interpreted with caution. A comparison of free-catch- and cystocentesis-obtained samples may be useful in cases of transition cell carcinoma that is located within the urethral and may not be visualized on ultrasound. In this latter example, there may be no transitional cells in the cystocentesis sample, but many transitional cells in the free-catch sample.

Urine culture

Especially in cats > 10 years, cats with previous catheterizations and cats with repeat episodes of iFLUTD. A urine culture can also confirm sterile urine in the face of pyuria that is typical of iFLUTD.

Complete blood count

To evaluate for evidence of inflammation or non-regenerative anemia that would implicate an upper urinary tract issue. Lower urinary tract inflammation should not cause a systemic inflammatory leukogram.

Biochemistry panel

To identify other co-existing diseases that might be exacerbating clinical signs. For example, cats with renal disease are polyuric-polydipsic which may be contributing to the periuria that may be present with iFLUTD. It's important to note, however, that renal disease does not cause or result in iFLUTD.

Radiographs

To rule out radiodense urolithiasis and this is the next most common cause, the first being iFLUTD, of LUTS. The most likely offenders in cats are calcium oxalate followed by struvite, both radiodense. The increased prevalence of calcium oxalate stones relative to struvite stones that has taken place in the last 10 or so years is likely associated with the attention to ash content and, more importantly, urinary pH effects in commercial cat foods. Interestingly, struvite urolithiasis is again on the rise in the last 3-5 years.

Ultrasound

To obtain a urine sample in some cases of very small irritated bladders; to rule-out the more uncommon non-radiodense stones; to assess for bladder abnormalities or presence of tumor; to assess renal architecture.

Contrast cystourethrogram

If urethral disease or diverticuli are suspected and catheterization is possible.

Review of therapies

The difficulty in evaluating the efficacy of therapies for iFLUTD is that this disease is self-limiting, resolving within 5-10 days regardless of therapy used. Several goals of therapy have been identified and various therapies addressing each aim have been investigated to one degree or another.

Alleviate pain and inflammation

• Amitriptyline [10 mg tabs] 5-10 mg/cat/day: a tricyclic anti-depressant drug that also has numerous other effects including anticholinergic, antihistamine, anti-alpha-adrenergic, anti-inflammatory and analgesic. In one study, 9 of 15 chronic iFLUTD cats had decreased clinical signs with long-term use of amitriptyline. However, another study found no short-term improvement in clinical signs in acute cases. Amitriptyline can cause somnolence, decreased grooming and weight gain.

• NSAIDS: ketoprofen, piroxicam and meloxicam have been used with some anecdotal success, but few controlled prospective studies have been performed. Prior to use of any NSAID, careful attention must be given to the hydration status and renal function in the patient.

• Glucocorticoids showed no difference in clinical signs or recurrence in control cats versus those receiving glucocorticoids and are therefore not recommended, especially if given in concurrence with NSAIDs.

• Antispasmodics (Valium, phenoxybenzamine, propantheline): The few available studies showed no significant differences in outcome in cats administered these various antispasmodics. Phenoxybenzamine (2.5-10 mg [total dose] PO q24h) did show some decreased pre-prostatic urethral pressures suggesting some benefit of this drug for acute cases.

Supplement GAGs (optional)

• Pentosan polysulfate (2 to 16 mg/kg BID. or 8 mg/kg BID PO): as a GAG replacement. The treatment has been shown to be helpful in some human patients and a veterinary product (Cartrophen) has been used successfully in some cats. Elmiron is the human product available in the United States, but does need to be formulated to smaller capsule sizes. Side effects can include bleeding/bruising as it is a heparin-like compound, though this has not specifically been reported in cats.

• Oral glucosamine (125 mg glucosamine, 100 mg chondroitin sulfate, PO daily for cats < 10 lb; 1 capsule PO BID for cats > 10 lb): one study showed no significant difference between FIC cats receiving oral glucosamine versus a placebo.

Alleviate stress

• Multimodal Environmental Modification (MEMO): Provide multiple litter boxes for multiple cat households; be fastidious about keeping the litter boxes clean; limit stressful events if the cat is prone to episodes of iFLUTD. One study showed significant improvement in fear, nervousness, URIs and a trend to decreased aggression in cats for which MEMO was implemented. There was no recurrence of clinical signs in 70-75% of cats in this 10-month study.

• Use of synthetic feline facial pheromone (Feliway) resulted in a trend (though no statistically significant difference) for fewer days of clinical cystitis and a reduced number of episodes of FIC as two of the more important findings in a clinical study.

Increase water intake

Several studies that were evaluating dietary and or other supplementations in the treatment of FIC in cats concluded that the main correlation between improvement in clinical signs and/or recurrences was a canned diet. Therefore, canned diets, because of their increased water content, and encouraging water consumption, is one of the advocated therapies for FIC.

Recommendations

There are no therapies that have been shown to decrease the duration of acute episodes of iFLUTD, so the focus in the management of these cases is fluids and pain management. Phenoxybenzamine may be helpful in treating the urethral spasms that occur during these episodes. Long-term therapy for chronic, recurrent cases should include increasing water intake which is most easily achieved by feeding a canned diet and alleviating stress with the use of MEMO and Feliway®. Glucosamine and amitriptyline could be added in these cases as some evidence suggest these may be helpful in these chronic cases.

References

Gunn-Moore DA. Proceedings of the ESFM Feline Congress (Stockholm, 2002): Feline lower urinary tract disease. J Fel Med & Surg 2003;5:133-138.

Chew DJ, Buffington CAT, Kendall MS. Amitriptyline treatment for severe recurrent idiopathic cystitis in cats. JAVMA 1998;213:1282-1286.

Osborne CA, Kruger JM, Lulich JP. Prednisolone therapy of idiopathic feline lower urinary tract disease: a double-blind clinical study. Vet Clin North Am Small Anim Pract 1996 ;26:563-569.

Gunn-Moore DA, Shenoy CM. Oral glucosamine and the management of feline idiopathic cystitis. J Fel Med & Surg 2004;6:219-225.

Gunn-Moore DA, Cameron ME. A pilot study using synthetic feline facial pheromone for the management of feline idiopathic cystitis. J Fel Med & Surg, 2004;6:33-138.

Markwell PJ, Buffington CAT, Chew DJ, et al. Clinical evaluation of commercially available urinary acidification diets in the management of idiopathic cystitis in cats. JAVMA 1999;214:361-365.

Buffington CAT, Westropp JL, Chew DJ, et al. Clinical evaluation of multimodal environmental modification (MEMO) in the management of cats with idiopathic cystitis. J Feline Med Surg 2006;8(4):261-268.