Feline Lower Urinary Tract Diseases

Terminology

Feline Urologic Syndrome (FUS)

In 1970, the term "feline urologic syndrome" and the acronym "FUS" were first used and soon became widely adopted as a diagnostic umbrella to refer to naturally occurring and experimentally induced feline lower urinary tract disease (FLUTD) with different sites of involvement, different combinations of clinical signs, and fundamentally different underlying causes [1]. The common denominator of all of these disorders was varying combinations of recurrent dysuria, pollakiuria, stranguria, hematuria, periuria (urinating in inappropriate locations), and/or urinary outflow obstruction. The similarity of clinical signs of FLUTD caused by diverse causes is understandable since the urinary tract can respond to various diseases in only a limited and predictable fashion. Unfortunately, use of the acronym FUS to lump all FLUTDs together, rather than separating them on the basis of specific underlying causes, fostered fundamental errors in the design of experimental, epidemiologic, and clinical studies designed to investigate the biologic behavior and diagnosis of this problem [2]. In addition a diagnosis of FUS based solely on history and physical examination findings resulted in a stereotyped approach to medical and surgical treatment and prevention of obstructive and nonobstructive LUTD, regardless of underlying cause.

Feline Lower Urinary Tract Disease (FLUTD)

In the early 1980's we advanced the concept that FUS was a poor synonym for a heterogeneous group of FLUTD that resulted from fundamentally different causes [2,3]. The causes may be single, multiple, and interacting or unrelated. This change in perspective with which we consider the naturally occurring forms of feline lower urinary tract disorders is of fundamental clinical significance because it helps to eliminate the stereotyped approach to treatment and prevention fostered by use of FUS as a diagnostic endpoint. We continue to urge our colleagues to substitute a clinical diagnosis of FUS with refined diagnostic terms pertaining to sites (e.g., urethra, bladder), causes (e.g., anomalies, urolithiasis, bacteria, fungi, parasites, neoplasms, metabolic disturbances, idiopathic forms), morphologic changes (e.g., inflammation, neoplasia), and pathophysiologic mechanisms (e.g., obstructive uropathy, reflex dyssynergia) whenever possible. If the cause of FLUTD cannot be identified after appropriate evaluation, we suggest that it be called idiopathic FLUTD with the understanding that not all cases of idiopathic FLUTD have the same underlying cause. Idiopathic FLUTD is an exclusion diagnosis.

Feline Idiopathic Cystitis and Feline Interstitial Cystitis

In the early and mid-1990's, investigators hypothesized that cats with idiopathic forms of LUTD had interstitial cystitis because they observed that some cats had abnormalities similar to those reported in humans with interstitial cystitis [4,5]. Human interstitial cystitis is a nonmalignant neuro-inflammatory disorder of humans of unknown etiology [6]. The disease is characterized by dysuria, pain above the pubic region which is relieved by voiding; dysuria; pyuria, hematuria, and/or proteinuria detected by urinalysis; distinctive petechial hemorrhages in the submucosa (called glomerulations) detected by cystoscopy; and decreased urine concentrations of glycosaminoglycans. In subsequent pilot studies of cats, decreased urine concentrations of glycosaminoglycans and increased urinary bladder permeability were also reported [7]. Therefore, they recommended that idiopathic LUTD be renamed feline interstitial cystitis (FIC). Since that time they have stated that use of the term feline interstitial cystitis as an umbrella term for all cats with idiopathic FLUTD is inappropriate . They reserve use of the term feline interstitial cystitis for cats that have persistent or frequent recurrence of clinical signs of lower urinary tract disease. Idiopathic FLUTD can be acute or chronic, but interstitial cystitis by definition is an idiopathic chronic inflammatory process. Currently, the terms idiopathic FLUTD and feline idiopathic cystitis are often used as synonyms.

Incidence and Proportional Morbidity of LUTD

Incidence

The incidence of disease is defined as the annual rate of appearance of new cases of disease among the entire population of individuals at risk for the disease. The overall incidence of feline FLUTD in the United States and Great Britain has been estimated to be 1.5% per year [8,9]. Although idiopathic disease currently accounts for the majority of these cases [5,10], the actual incidence of idiopathic disease, its rate of recurrence, and frequency of sequelae are unknown. There have been no contemporary controlled epidemiologic studies designed to evaluate subsets of cats with LUTDs defined on the basis of specific diagnostic criteria.

Proportional Morbidity Rates

The incidence of naturally occurring hematuria, dysuria, and/or urethral obstruction in domestic cats should not be confused with the frequency that such cats are seen in veterinary hospitals (so-called proportional morbidity rates). As apparent in the following discussion, proportional morbidity rates for FLUTD are not a reliable index of FLUTD incidence, since they may be affected by factors such as local population economics, geography, season, type of veterinary practice, and the interest and training of veterinarians.

Results of a recent retrospective study indicate that the proportional morbidity of FLUTD at Veterinary Teaching Hospitals from 1980 to 1997 was 8%, with significant variation between hospitals (3%-13%) [11]. The wide variance reported by veterinary teaching hospitals emphasizes the need for caution in formulating generalities about proportional morbidity rates of LUTD on the basis of reports from one center. Lower urinary tract disease is more commonly encountered and/or recognized in Veterinary Teaching Hospitals with special interests in FLUTD. Although proportional morbidity rates reported by these centers are unlikely to be representative of veterinary hospitals without a special interest in urology, the frequency with which specific causes of LUTD are recognized by contemporary diagnostic evaluation suggests that specific causes of LUTD are "under-diagnosed".

Results of prospective studies performed at two Veterinary Teaching Hospitals indicate that the most commonly encountered forms of FLUTD are idiopathic LUTD (~65 %) and urolithiasis (~25%) [5,10]. Diseases encountered less frequently include bacterial urinary tract infections, congenital defects, neurogenic disorders, neoplasia, and trauma [9,11].

Priority of Diagnostic and Therapeutic Plans for Lower Urinary Tract Diseases

Logically, in order to localize and define different causes of diseases of FLUTD, the need for contemporary diagnostic evaluation of each patient becomes indisputable. In addition to an appropriate history and physical examination, complete urinalysis performed on samples that have not been altered by reverse flushing solutions, and evaluation of the urinary tract by survey abdominal radiography or ultrasonography should be performed. Screening quantitative urine cultures are indicated if pyuria is identified by urinalysis. Contrast radiography and/or endouroscopy may be required to aid in localization of problems in addition to identifying the underlying cause(s) of persistent or recurrent clinical signs. Localizing the site(s) and cause(s) of urethral obstruction is especially important if urethral surgery is being considered. A neurologic examination may also be helpful. Patients with renal dysfunction caused by urethral obstruction should be evaluated with the aid of complete blood cell counts, and serum chemistry profiles (especially potassium and bicarbonate concentrations), and perhaps electrocardiograms (for evaluation of the toxic effect of elevated serum potassium concentration on the heart). Quantitative mineral analysis of uroliths and urethral plugs should be routine. Tissue removed surgically should be evaluated routinely by light microscopy.

If the cause of feline lower urinary tract disease cannot be identified after appropriate evaluation, the terminology idiopathic FLUTD or feline idiopathic cystitis (FIC) is recommended.

Developmental Abnormalities

As with other species, congenital abnormalities of the lower urinary tract may be associated with hematuria, dysuria, urinary incontinence, and/or urethral obstruction [9]. However, these causes of FLUTD are uncommonly recognized. Vesicourachal diverticula are an exception to this generality as they have been diagnosed in as many as 1 of 4 cats with lower urinary tract disease. They are worthy of further discussion.

Vesicourachal Diverticula

Function and Dysfunction of the Urachus

The urachus is a fetal conduit that allows urine to pass from the developing urinary bladder to the placenta. It becomes nonfunctional at birth. Microscopic remnants of the fetal urachus characterized by microscopic lumens lined by transitional epithelium have been detected at the bladder vertex in adult healthy cats. In a study of 80 feline urinary bladders, more than 40% had microscopic urachal diverticula.

Microscopic remnants persisting in the urinary bladder vertex after birth usually are clinically silent, but represent a risk factor for development of development of macroscopic diverticula of the urinary bladder in adult cats [12]. Abnormal and/or sustained increase of bladder intraluminal pressure associated with feline lower urinary tract disorders may cause enlargement and/or tearing of microscopic diverticula leading to development of self-limiting macroscopic diverticula of varying size.

Congenital and Acquired Vesicourachal Diverticula

In our experience, radiographically detectable diverticula affecting the vertex of the urinary bladder wall occur in almost 1 of 4 adult cats with hematuria, dysuria, and/or urethral obstruction [12,13]. They occur twice as often in male (27%) as female (14%) cats. We have not observed a breed predisposition. The mean age of affected cats at the time of diagnosis in our series was 3.7 years (range = 1 to 11 years); clinical signs of LUTD were not observed when the cats were younger than one year of age. The higher frequency of occurrence of vesicourachal diverticula in males compared to females is likely related to the higher prevalence of urethral outflow obstruction in males.

There are two etiologically distinct forms of macroscopic vesicourachal diverticula. In cats with the most common form, microscopic remnants of the urachus located at the bladder vertex remain clinically silent until lower urinary tract disease develops. Radiographically detectable diverticula may develop at the bladder vertex as a result of enlargement of these microscopic vesicourachal remnants following onset of increased intraluminal pressure caused by acquired urethral obstruction and/or detrusor hyperactivity induced by inflammation. This hypothesis is supported by the observation that many macroscopic diverticula in cats resolve within 2 to 3 weeks after amelioration of clinical signs of lower tract disease [13].

The second uncommon form consists of congenital macroscopic vesicourachal diverticula [12]. Although the exact sequence of events resulting in their formation has not been defined, they appear to be caused by disorders that cause abnormally high or sustained pressure in the bladder lumen. Congenital macroscopic vesicourachal diverticula typically are associated with signs of LUTD in immature cats. In our experience, they do not spontaneously resolve. Persistent congenital macroscopic diverticula predispose to bacterial urinary tract infections. If infections are caused by urease producing calculogenic microbes (especially staphylococci), infection induced struvite uroliths often develop.

Urachal diverticula are an uncommon primary factor in development of feline lower urinary tract disease. Most macroscopic diverticula of the bladder vertex are a sequela of lower urinary tract dysfunction. Furthermore, most macroscopic diverticula may be self-limiting if the urinary bladder and urethra return to a normal state of function [12,13]. Acquired diverticula usually heal within 2 to 3 weeks following elimination of the underlying cause of increased intraluminal pressure [13].

Uroliths and Urethral Plugs

The urinary system is designed to dispose of waste products in soluble form. However, some waste products are sparingly soluble and occasionally precipitate out of solution to form crystals. Growth or aggregation of microscopic crystals may lead to formation of macroscopic uroliths. Urolithiasis may be conceptually defined as the formation of uroliths from less soluble crystalloids of urine as a result of multiple genetic and/or acquired physiologic and pathologic processes. If such crystalloids become trapped ions the urinary system, they may grow to sufficient size to cause clinical signs.

Urolithiasis should not be thought of as a specific disease, but as a sequelae to one or more underlying abnormalities. Epidemiologic studies indicate numerous pathophysiologic, demographic, and environmental risk factors may be associated with the clinical expression of urolithiasis. Therefore, detection of uroliths is only the beginning of the diagnostic process. Determination of their mineral composition narrows etiologic possibilities. Knowledge of the patient's age, gender, diet, environment, and urine concentrations of calculogenic minerals, crystallization promoters, crystallization inhibitors, and their interactions provide additional insight into the diagnosis and management of uroliths.

Terminology

There are physical and probable etiopathogenic differences between feline uroliths and urethral plugs. Therefore, these terms should not be used as synonyms.

Uroliths are polycrystalline concretions composed primarily (> ~95%) of minerals (organic and inorganic crystalloids) and smaller quantities (< ~5%) of matrix. Unlike urethral plugs, uroliths are not disorganized precipitates of crystalline material, but are comprised of crystal aggregates with a complex internal structure.

Feline urethral plugs commonly are composed of large quantities (> ~50%) of matrix mixed with minerals [15]. However, some urethral plugs are composed primarily of matrix, some consist of sloughed tissue, blood, and/or inflammatory reactants, and a few are composed primarily of aggregates of crystalline minerals. They may form a cast of the urethral lumen, implying a rapid rate of formation.

The mineral composition of uroliths and urethral plugs should be used to describe them since most therapeutic regimes have been based on their mineral composition. A variety of different minerals have been identified in uroliths and urethral plugs of cats.

Epidemiology of Uroliths and Urethral Plugs

Uroliths

In 2004, 8711 feline uroliths were submitted by veterinarians to the Minnesota Urolith Center for mineral analysis. Struvite was the primary component in 45 percent of the uroliths, calcium oxalate was the primary component in 44%, and salts of uric acid were the primary component in 5%. Less than 1% of the uroliths were composed of calcium phosphate and cystine.

Urethral Plugs

In 2004, 524 feline urethral plugs were submitted by veterinarians to the Minnesota Urolith Center for mineral analysis. Struvite was the primary component in 87 percent of the uroliths, while 10% of the plugs contained noncrystalline matrix. Less than 1% of the uroliths were composed of calcium oxalate and calcium phosphate.

Uroliths

Biologic Behavior of Uroliths

Overview

Detection of a urolith is not always justification for surgical management. In cats, small uroliths may remain asymptomatic within the urinary tract (especially the renal pelvis and urinary bladder) for months or years. However, the underlying cause(s) of uroliths and the sequela of uroliths (partial or total obstruction, urinary tract infection) remain potential hazards. In those situations in which uroliths are fortuitously detected in asymptomatic patients without significant bacteriuria, minimizing risk factors by medical management and monitoring urolith activity by appropriate procedures is an accepted alternative to surgery. If the urolith(s) remain inactive, therapy designed to dissolve or remove them is not mandatory. If the urolith(s) become active, appropriate medical and/or surgical therapy are recommended.

Rate of Formation

The rate of formation of uroliths varies from days to months, being influenced by mineral composition, and a variety of risk factors. Once crystals of one mineral type form in urine, they may reduce the amount of lithogenic substances required for other mineral types of crystals to form. The principle involved is called heterogeneous nucleation (or "seeding") and operates in the same way as when foreign substances like suture material or catheters predispose to formation of uroliths. Viewed in this context, a crystal of one mineral type serves as a risk factor for formation of crystals of other types, and provides one explanation of why macroscopic uroliths may contain more than minerals.

Movement of Uroliths

Small uroliths that form in the urinary bladder may pass into the urethra of male or female cats. Because of the tendency of uroliths to change in size and position, radiographic evaluation of the urinary system should be repeated if there has been a significant time lapse between diagnosis and surgery scheduled to remove them.

Recurrence

Cats that have formed uroliths are at increased risk for recurrent stone formation. In our experience, sterile struvite uroliths have recurred within weeks to several months after elimination. Cystine uroliths also may recur within a few weeks to several months following removal. Calcium oxalate, calcium phosphate and ammonium urate uroliths also have an unpredictable tendency to recur, typically within months or years (rather than weeks) following removal.

Pseudorecurrence

Because many feline uroliths are small, complete surgical removal of all uroliths may be difficult. In a retrospective clinical study performed at the University of Minnesota, uroliths were detected by radiographs taken within 14 days following cystotomies in 20 percent of the patients [16]. We call this phenomenon pseudorecurrence. Results of this study emphasize the importance of postsurgical radiography, ultrasonography, or uroendoscopy to assess urolith status prior to evaluating recurrence and/or therapeutic efficacy.

Ammonium Urate Uroliths

In the series of feline uroliths from the Minnesota Urolith Center, ammonium urate and uric acid collectively called purines comprised approximately 6 percent of the total. The urinary bladder and urethra were the most common sites of purine uroliths (99%), while kidneys and ureters (<1%) were less common sites. In our series, males were affected as often as females. The mean age of affected cats was 6.1±3.1 years (range = 5 months to 15 years).

Although portovascular anomalies associated with hyperammonemia and hyperuricemia have been confirmed as the underlying cause in a few cases of urate uroliths in cats, the cause(s) of formation of most urate uroliths has not been established. However, formation of ammonium urate uroliths is likely to be associated with several risk factors (Table 67-1).

Calcium Oxalate Uroliths

The underlying cause(s) of calcium oxalate urolith formation has not been defined. Risk factors incriminated include age, gender, breed, hypercalciuria, hyperoxaluria, decreased urine concentration of crystallization inhibitors, hypocitrituria, hypomagnesuria, acidosis, increased urine concentration, decreased urine volume, and urine retention (Table 67-2). Several nutritional risk factors have also been incriminated.

The frequency of detection of calcium oxalate urolithiasis in cats has increased in recent years. In 2004, calcium oxalate uroliths comprised approximately 44% percent of the feline uroliths submitted to the Minnesota Urolith Center. Although calcium oxalate uroliths were located primarily in the urinary bladder (72%), they were also found in various combinations in the kidneys, ureters, and urethra.

Calcium oxalate uroliths may occur at any age. However, they are recognized more frequently in older cats. In one study, cats older than 7 years, but less than 10 years were 67 times more likely to develop calcium oxalate uroliths than cats 1-2 years of age [17]. In our series, male cats (57%) were affected more than females (43%). Neutered cats were 7 times more likely to form uroliths than sexually intact cats. Case control epidemiologic studies indicate increased risk of calcium oxalate uroliths in Burmese, Himalayan, and Persian, British and exotic shorthair, Havana brown, ragdoll, and Scottish fold breeds suggesting that genetic factors may enhance risk in some cats [9,17,18,19].

In most cats with calcium oxalate uroliths, serum concentrations of minerals, including calcium, have been normal. The sequence or sequences of events that promote initiation and growth of calcium oxalate uroliths in normocalcemic cats have not been defined. However, epidemiologic studies have identified several probable risk factors (Table 67-2) [20,21]. Mild hypercalcemia (11.1 to 13.5 mg/dl) has been observed with sufficient frequency (35%) to warrant routine evaluation of serum total calcium concentration in affected patients [21]. The mechanism(s) of hypercalcemia has not been identified in most cats. Hypercalcemia promotes urinary calcium excretion, and may result in precipitation of calcium oxalate crystals. If hypercalcemia is confirmed in serially obtained serum samples, serum ionized calcium, parathormone, and vitamin D concentrations should be evaluated.

Cats with calcium oxalate urolithiasis typically have acid (urine pH of 6.3 to 6.7) urine. Pretreatment blood pH and total carbon dioxide concentration are often reduced (pH = 7.3). However, the solubility of calcium oxalate crystals is apparently not directly influenced by urine pH within the physiologic range. The indirect association between aciduria, acidemia, and calcium oxalate urolithiasis may be that acidemia promotes mobilization of carbonate and phosphorus from bones to buffer hydrogen ions. Concomitant mobilization of bone calcium may result in hypercalciuria. Hypercalciuria in turn is a risk factor for calcium oxalate crystals. In addition, low urine pH decreases urinary citrate concentration by promoting renal tubular reabsorption of citrate. Results of epidemiologic studies support this association inasmuch that cats with calcium oxalate uroliths were 3 times more likely as hospitalized cats to have been fed diets that promote urine pH values less than 6.3. [18,22].

Several diet related risk factors may be associated with calcium oxalate uroliths. Urine acidifying potential and the effect of water consumption on urine volume and concentration are especially important.

Although reduction of urine calcium and oxalic acid concentrations by reduction of dietary calcium and oxalic acid appears to be logical goals, they are not necessarily a harmless maneuvers. Reducing consumption of only one of these constituents (such as calcium) may increase the availability of the other (such as oxalic acid) for intestinal absorption and subsequent urinary excretion [9,20,22]. Based on recent epidemiologic information suggesting that marked dietary calcium restriction is associated with increased risk for calcium oxalate urolith formation, the general consensus of opinion is that restricting dietary calcium is inadvisable. Moderate levels of dietary calcium are recommended in normocalcemic cats.

In one study, consumption of higher levels of sodium augmented renal excretion of calcium in healthy cats, but reduced supersaturation of urine with calcium oxalate [20]. The explanation of this paradox may be that the effects of oral sodium on water intake and its diluting effect on urine calcium concentration were greater than the effect of sodium on promoting urine calcium excretion. However, studies of cats with naturally occurring calcium oxalate uroliths revealed that consumption of a low sodium diet designed to minimize recurrence of calcium oxalate uroliths was associated with reduced urine calcium concentration and reduced supersaturation of urine with calcium oxalate [23]. Based on this evidence, moderate dietary restriction of sodium would be a logical recommendation for active calcium oxalate urolith formers.

Dietary phosphorus should not be restricted in patients with calcium oxalate urolithiasis because reduction in dietary phosphorus may be associated with activation of vitamin D, which in turn promotes intestinal calcium absorption and subsequent urinary calcium excretion. In addition, pyrophosphate is an inhibitor of calcium oxalate urolith formation [22].

Increased urine magnesium concentration reduces formation of calcium oxalate crystals in vitro [9]. For this reason, supplemental magnesium has been used to minimize recurrence of calcium oxalate uroliths in man. However, supplemental dietary magnesium may contribute to formation of magnesium ammonium phosphate uroliths and hypercalciuria in cats. On the other hand, epidemiologic studies suggest that cats fed foods with reduced magnesium and urine acidifying capabilities are at risk for developing calcium oxalate uroliths. Pending further studies, we do not recommend dietary magnesium restriction or supplementation for cats with calcium oxalate uroliths [20,24].

Ingestion of foods that contain high quantities of animal protein may contribute to calcium oxalate urolithiasis by increasing urinary calcium and oxalic acid excretion, and by decreasing urinary citric acid excretion. Some of these consequences result from obligatory acid excretion associated with protein metabolism. However, because cats are obligatory carnivores, dietary protein restriction is not recommended.

Epidemiologic studies performed at the University of Minnesota revealed that cats consuming canned diets had one third the risk for calcium oxalate urolith formation compared to other dietary formulations [22]. Increased urine volume could minimize formation of uroliths by reducing the concentration of calculogenic substances in urine, and also by promoting voiding before crystals have an opportunity to grow of sufficient size to cause clinical disease. Total water consumption is often less in cats fed dry diets resulting in formation of a lower volume of highly concentrated urine.

In summary, based on contemporary knowledge, diets that minimize calcium oxalate urolithiasis should be formulated to minimize acidosis, and should not contain excessive oxalic acid precursors. Likewise, excessive levels of vitamin D (which promote intestinal absorption of calcium), ascorbic acid (a precursor of oxalate), and sodium should be avoided. They should contain adequate, but not excessive, quantities of calcium, phosphorus, magnesium, potassium, and citrate. The diet should be adequately fortified with vitamin B6 since vitamin B6 deficiency promotes endogenous production and subsequent urinary excretion of oxalic acid. Canned diets are preferred over dry formulations to enhance formation of less concentrated urine and to promote increased micturition.

Struvite Uroliths

Results of our clinical and experimental studies indicate that two distinct etiologic mechanisms may be responsible for development of uroliths containing large quantities of struvite [9]. Formation of sterile struvite uroliths (perhaps in association with dietary risk factors) is the most common type. Formation of "infected" or "urease" struvite uroliths as a sequela to urinary tract infection with urease producing bacteria is a second type.

In 2004, approximately 45 percent of the naturally occurring feline uroliths submitted to the Minnesota Urolith Center were primarily struvite. Although the exact percentage of sterile versus infection-induced struvite uroliths in this series could not be precisely determined, we estimate that at least 90 percent to 95 percent were composed of sterile struvite. The remainder of this discussion pertains to sterile struvite uroliths. Information about infection-induced struvite is described elsewhere [2].

Compared to cats that develop calcium oxalate uroliths, cats with struvite uroliths tend to be younger. Cats ≥4 years of age but ≤7 years of age had the highest risk for developing struvite uroliths [17]. Struvite uroliths occur more commonly in females (55%) than males (45%). A case control comparison performed at the University of Minnesota revealed increased risk in domestic shorthair, foreign shorthair, oriental shorthair, ragdoll, Chartreux, and Himalayan breeds [17]. Neutered cats were 3.5 times more likely to develop struvite uroliths as sexually intact cats. The urinary bladder was the most common site of detection of struvite uroliths, while the kidneys, ureters, and urethra were less common sites.

Data derived from cats with induced sterile struvite uroliths indicate that several dietary factors play a role in the etiopathogenesis of naturally occurring sterile struvite uroliths. Of these, factors affecting urine magnesium concentration, urine pH, and urine concentration are of major therapeutic importance [9,20]. A decrease is urine volume and increase in urine specific gravity secondary to decreased water consumption would be a logical risk factor for urolith formation (Table 67-3). Likewise, excessive consumption of food (perhaps associated with ad libitum feeding) would be expected to result in obesity and excretion of excess minerals (some of which could be calculogenic) in urine. Cats maintain magnesium homeostasis by excreting excessive dietary magnesium in their urine.

Urethral Plugs

Urethral plugs contain varying quantities of minerals in proportion to large quantities of matrix. Although a variety of different minerals have been identified in urethral plugs of cats, struvite is the most common. Of 524 feline urethral plugs submitted to the Minnesota Urolith Center in 2004, the primary mineral composition of approximately 87% was struvite. Less than 1% was composed of calcium oxalate or calcium phosphate.

Risk factors associated with the formation of calcium oxalate, calcium phosphate, and magnesium ammonium phosphate crystals found in urethral plugs are probably similar to those associated with mineral formation in classic uroliths. The mineral composition of urethral plugs should be used to describe them, at least in part, since therapeutic regimes are often influenced by knowledge of their mineral composition.

Compared to uroliths, urethral plugs contain large quantities of matrix. Some urethral plugs do not contain crystalline components; 10% of the plugs evaluated in 2004 contained only noncrystalline matrix. The question about specific composition of urethral plug matrix has not yet been answered. However, it appears as though the amorphous matrix traps crystals and non- crystalline structures (including red blood cells, white cells, epithelial cells, spermatozoa, virus-like particles, and bacteria) in a manner analogous to the formation of fruit Jello [25].

Bacterial Urinary Tract infections

Initial episodes of LUTD in young adult cats usually occur in absence of significant numbers of detectable aerobic bacteria [26,27]. In prospective diagnostic studies of male and female obstructed and nonobstructed cats, aerobic bacterial urinary tract infections were identified in less than 3% of patients [5,10]. The infrequency with which aerobic bacteria have been isolated from urine of young adult and middle age cats during the initial phases of LUTD is related to highly effective local host defense mechanisms in this species [26].

Although bacterial UTI is encountered in only 1 to 3% of young adult cats, the prevalence of UTI increases to 10% or greater in cats 10 years of age or older [11,28]. The frequency with which bacterial UTI has been recognized in geriatric cats with LUTD should prompt appropriate diagnostic evaluation in this population of clinical patients.

When bacterial UTI has been detected in cats, it usually is a secondary or complicating factor rather than as a primary etiologic factor. Local urinary tract defenses against bacterial infection are frequently compromised in cats with various forms of naturally occurring nonbacterial LUTD, especially if the episode is associated with urethral obstruction.

Use of indwelling transurethral catheters is associated with a high prevalence of secondary or complicating bacterial urinary tract infection. In studies of normal cats, and cats with induced LUTD, catheter-induced bacteriuria was detected in 33% of cats after 1 day of catheterization, and in 50% to 83% of cats after 5 days of indwelling catheterization [29]. Bacterial UTI is also a common sequelae in cats following perineal urethrostomies. Consult the chapter entitled, "Bacterial Urinary Tract Infections" for further information.

Idiopathic Feline lower Urinary Tract Disease

Etiopathogenesis

In approximately 65% of naturally occurring cases of LUTDs, the exact cause(s) of hematuria, pollakiuria, stranguria, periuria, and/or urethral obstruction are still unknown. After appropriate diagnostic evaluation, these cats are classified as having idiopathic FLUTD, feline idiopathic cystitis (FIC), or feline interstitial cystitis. Because there is no pathognomonic test or diagnostic procedure, diagnosis of idiopathic LUTD is dependent on exclusion of other known causes.

Clinical observations suggest that stress may play a role in precipitating or exacerbating signs associated with idiopathic cystitis [30-32]. Neuroendocrine abnormalities identified in cats with chronic idiopathic cystitis are indicative of increased activity of the sympathetic nervous system and diminished adrenocortical responsiveness [33,34]. Based on these observations, strategies designed to normalize reactivity of the stress response system have been advocated to minimize recurrence of feline idiopathic cystitis.

Clinical Manifestations

Nonobstructive idiopathic FLUTD occurs in males and females of all ages, but more commonly in young to middle aged cats (mean 3.5 years, range 0.5-17.5 years) [5,10].

It is uncommon in cats less than one year and less common in cats older than 10 years. There are no apparent breed predilections.

Periuria, pollakiuria, stranguria, and gross hematuria are the most common clinical signs observed in cats with nonobstructive idiopathic FLUTDs and often precede the obstructive form of the disorder.

Unless complicated by concurrent illness, results of CBCs and biochemistry profiles of cats with nonobstructive idiopathic FLUTDs are usually normal. Urine obtained from cats with idiopathic FLUTDs is usually concentrated and acidic. Hematuria and proteinuria in the absence of pyuria or bacteriuria are typical urinalysis findings [9,35]. Although microscopic hematuria may be a consequence of cystocentesis-induced trauma, the observation of gross hematuria in 81% and microscopic hematuria in 95% of nonobstructed cats with idiopathic FLUTDs suggests that hematuria is a prevalent feature of idiopathic FLUTDs.

The prevalence, magnitude, and type of crystalluria are variable in cats with idiopathic FLUTDs and do not appear to differ from unaffected control cats [10]. Struvite crystals have been the most common crystal type identified in urine of cats with idiopathic FLUTDs. Undoubtedly, some instances of struvite crystalluria in these patients represent in vitro rather than in vivo formation.

Results of urine culture from cats with idiopathic FLUTDs have been negative for aerobic bacteria, mycoplasma, ureaplasma, and viruses. Most cats with idiopathic FLUTDs are seronegative for FIV antibodies and FeLV antigen [10,35].

Survey abdominal radiographs of cats with nonobstructive idiopathic FLUTD are usually normal. Contrast cystourethrography may be normal or may reveal thickening of the bladder wall, mucosal irregularities, urachal diverticula, and/or urethral narrowing. Ultrasonographic findings of idiopathic FLUTDs have not been characterized; however, blood clots and mural irregularities or thickening may be detected.

Cystoscopic examination of cats with nonobstructive idiopathic LUTDs may reveal increased mucosal vascularity, superficial urothelial desquamation, and petechial hemorrhages in the submucosa (so called "glomerulations") [7]. Glomerulations are nonspecific and may be associated with other urinary bladder disorders [6]. In addition, cystoscopy induced urothelial trauma may be confused with primary pathologic lesions. Pending results of additional studies, detection of glomerulations by cystoscopy should be interpreted in the context of the results of other diagnostic evaluations.

Exploratory cystotomy has been commonly used for diagnostic evaluation of idiopathic FLUTDs. With the advent of less invasive means of evaluating the lower urinary tract, the need for cystotomy and surgical biopsy of the urinary bladder for the sole purpose of establishing a diagnosis has largely been eliminated. Even when performed most biopsy samples reveal mucosal erosions and ulcerations, and varying degrees of submucosal hemorrhage, edema, and fibrosis. These light microscopic findings are nonspecific, and rarely lead to improved therapy. Therefore, we cannot recommend cystotomy over less invasive diagnostic procedures for establishing a diagnosis of idiopathic FLUTDs.

Biologic behavior of Idiopathic LUTD

Clinical signs of hematuria, dysuria, and pollakiuria in many untreated nonobstructed males and females with acute idiopathic FLUTDs frequently subside within 5-7 days. These signs may recur after variable periods of time and again subside without therapy. Our impression is that recurrent episodes of acute idiopathic LUTDs tend to decrease in frequency as the cats become older [37,38].

Though recurrent clinical signs in patients with idiopathic FLUTDs are often assumed to be recurrence of the original disease, recurrent signs may also be the result of a delayed manifestation of the original disease (for example, spontaneous or iatrogenic urethral stricture). In addition, onset of a different disease associated with clinical manifestations similar to those of the original disorder (such as urolithiasis) may occur.

Occasionally we have encountered cats with hematuria and dysuria that have persisted for weeks to months and for which a specific cause was not identified. Whether chronic idiopathic FLUTDs represent one extreme in the spectrum of clinical manifestations associated with similar etiologic factors, or whether it represents an entirely different mechanism of disease than that associated with acute self-limiting idiopathic disease is unknown.

Since clinical signs associated with this form of the disease are frequently self-limiting and of short duration, any form of therapy might appear to be beneficial, as long as it is not harmful. The self-limiting nature of clinical signs in many cats with idiopathic FLUTDs underscores the need for controlled prospective double-blind clinical studies in order to prove the efficacy of various forms of therapy.