Lower urinary tract disease in cats (Proceedings)

Lower urinary tract diseases of cats are a common, and sometimes frustrating, group of clinical problems that practitioners must deal with. Any disorder of the lower urinary tract may cause signs of lower urinary tract disease, the key is to understand the diseases that occur in cats and how they differ from the classic UTI/stone based diseases of dogs. In cats under 10 years of age, idiopathic cystitis (previously termed interstitial cystitis) is by far the most common cause of clinical disease, while in cats over 10 years of age, urinary tract infections are more common. The focus of this review is on the control, prevention and, where possible, treatment, of lower urinary tract disease in cats.

Feline interstitial cystitis

Feline lower urinary tract disease is condition characterized by painful, difficult or inappropriate urination (urinating outside the box), hematuria, and possibly the formation of stones in the urinary tract. The key is to recognize that there are many potential causes for the above symptoms: including crystalluria/urolithiasis, urinary tract infection or idiopathic. As many as 65% of cats under 10 years of age with lower urinary tract signs suffer from the idiopathic form of the disease – currently termed idiopathic cystitis – where there are no crystals, no UTI, no stones and no identifiable cause or if there are crystals or infection they are occurring secondary to interstitial cystitis as the primary cause. The classic progression of this disease is for the clinical signs to last 3-7 days with self resolution during that time (the reason why many have believed mistakenly that the signs resolved due to antibiotic or anti-inflammatory therapy). For these cats, no drug therapy to date has shown consistent benefit, and some drugs prescribed long term may have detrimental effects. However, in a controlled study, dietary therapy using a canned cat food diet designed to maintain a dilute urine and urine pH in the neutral range significantly reduced the rate of recurrence (90% did not recur over a 12 month trial period, compared to 60% of the control group). While there is still much to be learned about cats with idiopathic cystitis, increasing water intake and urine dilution appears to be very beneficial in the therapy of these cats.

Because the disease is associated with pain and mucosal hemorrhage due to defects in the bladder GAG layer – management is aimed at control of pain and prevention of complications of hemorrhage (blood clots forming concretions that cause an obstruction or nidus for crystal matrix formation). The inflammation associated with idiopathic cystitis in the bladder wall is not mediated by COX – mechanisms, thus, steroids or non-steroidal therapy will not result in significant control of discomfort. The most effective drug therapy for pain control in these cats appears to be opioids (buprenorphine or butorphanol). The best way to prevent clot formation or crystal nidus formation is to keep the urine as dilute as possible – thus, canned food, increasing water intake by other means, or giving SQ fluids are important aspects of therapy.

Finally cats with this disease, similar to humans with interstitial cystitis, appear to have co-morbid conditions as part of their disease: obesity, separation anxiety (and other stress responses) and hypertrophic cardiomyopathy. Research indicates that cats with idiopathic cystitis have an enhanced activation of the stress response system (sympathetic) from higher brain centers. Although more work is needed to fully understand this disease, therapy of idiopathic cystitis in cats should also be focused on methods of decreasing sympathetic responses. There is a website (www.indoorcat.org) that is dedicated to helping cat owners better understand this disease and indoor cat health.

Key aspects of urolithiasis

Development of urocystoliths in cats is a well known, and reasonably well-understood, phenomenon resulting from loss of solubilization of ions (primary Mg, NH4, PO4) or other minerals/substances found in urine (oxalate, urate, silica, cystine) in urine. The process is complex and requires a combination of preceding events to provide the appropriate environment for the formation of crystals and ultimately urinary stones.

• Normal urine inhibits the growth of crystals and formation of uroliths, it is under circumstances we will describe below that urine allows or promotes crystal formation.

• The formation of uroliths requires the three major components: 1) presence of ion or mineral in excess of its solubility product (supersaturated urine – metastable urine solution that may proceed either way – back to a stable solution or one to become oversaturated – unstable urine in which the concentration of ions is high and precipitation of solute occurs), 2) appropriate urinary environment for formation (pH), and, 3) a relatively concentrated urine that is not voided regularly to allow precipitation (nucleation) of the ion onto matrix.

• Prevention or control of uroliths in dogs or cats is based on alteration or management of one or all three of these aspects. First, this is accomplished by reducing the amount of mineral excreted by addressing medical or drug related causes (e.g. bacterial UTI, hyperadrenocorticism, portosystemic shunts, primary hyperparathyroidism, steroid therapy, etc) or via dietary reduction of these minerals to make them less available for excretion. Second, alteration or manipulation of urinary pH by dietary or drug therapy. And, third, by insuring the urine is dilute (specific gravity is <1.020) so that the minerals and ions present in urine are able to stay in solution.

There are a variety of types of urinary stones. Some types of stones are readily amenable to dietary dissolution and prevention, while others are not, so one of the most important steps in management of urolithiasis is to know what type of stone is present. In addition, it is important to recognize that while the presence of crystals in the urine may allude to a particular stone type (but doesn't prove the type or that stones are present), not all uroliths are of a single type –which will greatly complicate their management. Thus, surgical removal and stone analysis can be a very important component of diagnosis.

Feline uroliths

In the early 80's the primary type of urinary stone found in cats was composed of magnesium, ammonium and phosphate (in 1985, the number was 80% of all stones). However, in 1995, only 35% of the stones were struvite, and 54% of the stones submitted to the University of Minnesota Urolith Center were calcium oxalate. The primary reason for this decrease in struvite stones in cats was due to dietary manipulation of feline foods (low magnesium, low phosphorus, and adding urinary acidifiers to the diets). Further, because young cats rarely develop bacterial UTI, this aspect of struvite formation is not a consideration as it is for dogs. However, the result of producing low magnesium, low phosphorus, acidified diets has resulted in a shift in stone type that creates an incredibly bigger challenge: as calcium oxalate stones are much more difficult to manage.

Magnesium, ammonium, phosphate or struvite uroliths

• They form almost exclusively in alkaline urine, made so by the presence of dietary factors (protein is acidifying, high carbohydrate diets tend to alkaline urine, but high magnesium, ammonium and phosphate in diets increases risk), and urine volume.

• Of all of major stone diseases in cats, struvite stones are the most amenable to medical and dietary therapy, which includes:

1. Dietary dissolution of these stones can be achieved with short term use of a diet that is: 1) extremely low protein, magnesium, ammonium, phosphate, and 2) is highly acidified to lower urinary pH to less than 6.0. Because these diets are highly protein restricted (16% protein on a dry matter basis)– they should not be fed for long periods (4-6 months) or as a maintenance diet and should be discontinued if the stones are not dissolved in a 1-2 month period. Hill's Prescription Diet s/d is the primary diet available for dissolution of struvite uroliths, however, struvite stones will dissolve in any cat fed a diet that reduces the concentration of the substrate, decreases the urine pH, and increases the urine volume.

2. Prevention of struvite uroliths often times can be successfully achieved by using acidified diets formulated with lower levels of protein, magnesium, and phosphate (but not as restrictive as a dissolution diet). In addition, prevention or early correction of recurrent urinary tract infections is essential for the long term management of this type of stone disease.

3. There are a variety of diets commercially formulated for prevention and control of struvite uroliths. They include: Hill's Prescription diet c/d, RC/Waltham S/O, and RC/Innovative Veterinary Diets (IVD) Control. Eukanuba Senior Plus is recommended as an appropriate diet for dogs to prevent formation of struvite stones.

• In all cats with stones of this type, it is important to increase water intake (feeding canned foods is one way to increase fluid intake) to insure production of a more dilute urine. Maintaining more dilute urine by increasing water intake and urine volume is a very effective means of controlling urolith formation.

• In cats that do not respond to appropriate dietary therapy for prevention or dissolution of struvite stones REASSESS the diagnosis: Are the stones pure struvite or could the stones be compound stones (mixed with calcium)? Are there any confounding factors that can be addressed?

• Finally, frequently (q3-4mo) monitor the urine to be sure that you are achieving your goal: 1) urine specific gravity < 1.020, urine pH 6.5-7.0, and no evidence of magnesium, ammonium phosphate crystals in the urine sample.

Calcium oxalate (and other calcium containing stones)

The most common urinary stone type presently reported in cats is calcium oxalate. These stones are more difficult to manage via dietary or medical therapy. However, because they may be caused by identifiable medical or drug therapy – this is one of the most important aspects of therapy of these stones. Any disease process, diet, or drug that increases the excretion of calcium can lead to the development of calcium containing (oxalate, phosphate, apatite) stones. Thus, identification and correction of those causes, if possible, are extremely important in the management of these uroliths.

• Important medical causes of calciuria: hyperadrenocorticism, hyperparathyroidism, hypercalcemia due to Addison's disease, malignancy, vitamin D rodenticides, or infectious diseases.

• Important dietary associations with development of calcium oxalate uroliths are diets low in moisture (dry) or phosphorus (renal diets), high in vitamin D, or low in protein.

• Important drug causes of renal calcium loss are: steroids, furosemide, vitamin D, and high sodium containing fluids (0.9% sodium chloride).

• Calcium oxalate and other calcium containing stones tend to form in more acidic (< pH 6.5) urine. Thus, these stones may occur in cats being fed acidifying diets to prevent struvite uroliths. However, studies suggest that pH manipulation alone will not prevent their formation.

• Potassium citrate supplementation has been previously recommended to alkalinize urine and cause citraturia (to complex with calcium and prevent oxalate stone formation), however, no studies have been performed in cats to determine whether citrate does reduce oxalates.

• These stones cannot be dissolved by the use of dietary or drug therapy. So, surgical removal, prevention of reformation (if possible), and early detection of reformation are keys to appropriate management.

• An epidemiologic study, similar to that recently reported in dogs, evaluating the dietary risk factors for calcium oxalate stone formation has not been published in cats. However, the dissertation research of one of the authors of the canine study reports that in cats, high concentrations of calcium, magnesium, and phosphorus may be a risk factor for increasing oxalate uroliths in cats, whereas midrange concentrations were not.

• Diets high in moisture (canned) are still preferred over dry diets, even if the dry diets are high in protein, calcium, phosphorus or potassium for prevention of these stones.

• The goal is to keep the urine specific gravity dilute (< 1.020), the urine pH neutral to alkaline (pH 7.0-7.5), and to reduce calciuria by controlling any medical or drug related causes of increased urinary calcium excretion.

• Several commercially available diets have been recommended to control re-formation of calcium oxalate stones: Hill's Prescription diet XD, RC/Waltham S/O, Purina NF, and RC/IVD Modified.

• HOWEVER, a note of caution is suggested in using diets designed for renal failure (low phosphorus diets) as they have been proposed (in dogs with normal renal function) to trigger increased renal vitamin D production, resulting in increased calcium absorption from the gut and ultimately, increased calciuria. Whether or not this phenomenon occurs in cats is unknown.

• Because many cats with calcium oxalate stones have frequent recurrence of the stones, for which surgical removal is the only treatment once they are too large to be passed through the urethra – frequent re-evaluation (radiographs at 2-3 month intervals) is recommended, so that if stone reformation is observed, reassessment of the dietary prevention plan can be done.

References

1. Westropp JL, Buffington CAT. Etiopathogenesis of feline idiopathic cystitis. In: August JR, Consultations in Feline Internal Medicine. Elsevier, Philadelphia, p. 435, 2006.

2. Bartges JW, Kirk CA. Nutrition and lower urinary tract disease. Veterinary Clinics of North Am, 36: 1361, 2006.