Joe Bartges, DVM, PhD, DACVIM, DACVN Professor of Medicine and Nutrition The Acree Endowed Chair of Small Animal Research Department of Small Animal Clinical Sciences College of Veterinary Medicine The University of Tennessee Knoxville, TN Urine Heaven Page 1
Urolithiasis in Dogs and Cats Dogs and cats are often examined because of signs of lower urinary tract disease including hematuria, dysuria, pollakiuria, incontinence, and inappropriate urination. A review of data obtained from the Veterinary Medical Data Base between 1980 and 1995 revealed a prevalence of lower urinary tract disease in dogs of 3.0% (16,702 cases/561,028 individuals examined); between 1980 and 1990, the prevalence of lower urinary tract disease in cats was 7.3% (13,511 cases/184,983 individuals examined). Lower urinary tract disease is more prevalent in dogs older than 4 years of age, and in cats between 1 and 10 years of age (Figure 1). Figure 1. Prevalence of lower urinary tract disease in dogs (1980-1995) and cats (1980-1990) 12 10 8 6 4 2 0 D o g s C a t s 0 t o 1 1 t o 2 2 t o 4 4 t o 7 7 t o 10 10 t o 15 > 15 A ge (years) Urolith formation is not a specific disease, but the sequelae to a group of underlying disorders. The urinary system is designed to dispose of wastes in liquid form. However, during urolith formation, sustained alterations in urine composition promote supersaturation of one or more substances eliminated in urine, and result in their precipitation and subsequent growth. The fact that urolith formation is erratic and unpredictable emphasizes that several interrelated physiologic and pathologic factors are often involved. Therefore, detection of urolithiasis is only the beginning of the diagnostic process. Essential to urolith eradication and prevention is identification of the diseases and risk factors underlying crystal formation, retention, and growth. Regardless of the process in urolith formation, they all have the potential to disrupt normal urinary tract function. The mere presence of uroliths does not always necessitate their removal; however, those resulting in clinical signs (dysuria, hematuria, UTI, incontinence, obstruction, or azotemia) should be appropriately managed. Struvite Sterile struvite uroliths. Sterile struvite uroliths form typically in cats between 1 and 10 years of age. Risk for struvite urolith formation decreases after approximately 6-8 years of age in cats. They occur with equal frequency in male and female cats. Sterile struvite uroliths form because of dietary composition as well as innate risks for urolith formation. Experimentally, magnesium phosphate and struvite uroliths formed in healthy cats consuming calculogenic diets containing 0.15 to 1.0% magnesium (dry matter basis). These data are difficult to interpret, however, because the amount of magnesium consumption by cats in these studies may be different in than by cats that spontaneously form sterile struvite uroliths consuming commercial diets due to differences in caloric density, palatability, and digestibility. The influence of magnesium on struvite formation depends on urine ph and influence of ions, minerals, and other components in urine. Alkaluria is associated with increased risk for struvite formation. In a clinical study including 20 cats with naturally occurring struvite urocystoliths and no detectable bacterial urinary tract infection, the mean urinary ph at the time of diagnosis was 6.9 ± 0.4. An additional factor is water intake and urine volume. Consumption of increased quantities of water may result in lowering concentrations of calculogenic substances in urine, thus, decreasing risk of urolith formation. Consumption of small quantities of food frequently rather than one or two large meals per day is associated with production of more acidic urine and a lesser degree of struvite crystalluria by cats. Sterile struvite uroliths can be dissolved by feeding a diet that is magnesium, phosphorous, and protein restricted, and that induces aciduria relative to maintenance adult cat foods. In a clinical study including 22 cats with sterile struvite urocystoliths, urocystoliths dissolved in 20 cats in a mean of 36.2 ± 26.6 days (range, 14 to 141 days). The cats were fed a high-moisture (canned), calorically dense diet containing 0.058% magnesium (dry matter basis) and increased sodium chloride (0.79% dry matter basis). The diet (Prescription Diet Feline s/d, Hill s Pet Nutrition Inc.) induced a urine ph of approximately 6.0. Urine Heaven Page 2
Prevention of sterile struvite uroliths involves inducing a urine ph less than approximately 6.8, increasing urine volume, and decreasing excretion of magnesium, ammonium, and phosphorous. There are many diets available that are formulated to be struvite preventative. Infection-induced struvite uroliths: Infection-induced struvite uroliths occur more commonly in dogs and in cats less than 1 year and greater than 10 years of age. There is no published information on gender predilection for infection-induced struvite uroliths in cats; however, they are more likely to occur in female dogs. Infection inducedstruvite uroliths form because of an infection with a urease-producing microbe. In this situation, dietary composition is not important as the production of the enzyme, urease, by the microbial organism is the driving force behind struvite urolith formation. Infection-induced struvite uroliths can be dissolved by feeding a struvite dissolution diet and administering an appropriate antimicrobial agent based on bacteriological culture and sensitivity. Average dissolution time for infection-induced struvite uroliths is 8 weeks; however, it is dependent on the number and size of uroliths present. It is important that the dog or cat receive an appropriate antimicrobial agent during the entire time of medical dissolution as bacteria become trapped in the matrix of the urolith, and as the urolith dissolves bacteria are released into urine. If therapeutic levels of an appropriate antimicrobial agent are not present in urine, then an infection will recur, and dissolution will cease. Prevention of infection-induced struvite does not require feeding a special diet as the infection causes these struvite uroliths to form. It involves preventing a bacterial urinary tract infection from recurring and treating bacterial infections as they arise. Dietary manipulation will not prevent infection-induced struvite uroliths from recurring because diet will not prevent recurrence of a bacterial urinary tract infection. Calcium oxalate Calcium oxalate is the second most common mineral composition of uroliths in dogs and cats. It typically occurs in middle aged to older, male, small breed dogs and in middle aged to older male or female cats, especially those with long hair. The formation of calcium oxalate uroliths is poorly understand and undoubtedly involved multiple factors. Hypercalcemia results in hypercalciuria which may promote calcium oxalate formation; 35% of cats and 4% of dogs with calcium oxalate uroliths are hypercalcemic. The most common cause of hypercalcemia in cats with calcium oxalate uroliths is idiopathic hypercalcemia while in dogs with hypercalcemia and calcium oxalate uroliths it is primary hyperparathyroidism. Urocystoliths and urethroliths. Medical protocols that will promote dissolution of calcium oxalate uroliths are not currently available; therefore, uroliths must be removed physically. If urethral obstruction is present, uroliths should be retropulsed into the urinary bladder. Voiding urohydropropulsion can retrieve uroliths smaller than the narrowest part of the urethra. For larger uroliths, a cystotomy must be performed. Following surgery, abdominal radiography should be performed to insure that all uroliths have been removed. Calcium oxalate urocystoliths may be removed incompletely in approximately 20% of cases undergoing cystotomy. Occasionally, urethroliths cannot be retropulsed into the bladder because of the irregular surface contour of calcium oxalate uroliths. If located in the distal penile urethra, a perineal urethrostomy or urethrotomy should be considered. If uroliths are not causing clinical signs and surgery is not an option, measures may be taken to prevent further increase in size and number. Nephroliths and ureteroliths. Nephroliths and ureteroliths are commonly composed of calcium oxalate. Because calcium oxalate uroliths cannot be dissolved using medical protocols, surgical removal is the only option if the urolith must be removed. The decision to remove a nephrolith or ureterolith should be considered carefully because of long-term damage induced by nephrotomy. Upper urinary tract uroliths should be removed if they are causing obstruction resulting in diminished renal function, if they are associated with severe hematuria, pain, or persistent bacterial infection, or if they are increasing in size and damaging renal tissue. If none of these conditions are present, then a reasonable alternative approach may be to use preventative measures to minimize an increase in size or number of uroliths. Monitoring may be accomplished by performing abdominal radiography every 3-6 months. Extracorporeal shock wave lithotripsy (ESWL) has been successful in managing dogs with nephroliths and cats with ureteroliths, but availability is limited. Following surgical or non-surgical removal of uroliths, medical protocols should be considered to minimize urolith recurrence or to prevent further growth of uroliths remaining in the urinary tract. In animals with hypercalcemia, the cause of hypercalcemia should be investigated and corrected if possible (e.g. dogs with primary hyperparathyroidism). In dogs, 2 dietary strategies can be employed for prevention of calcium oxalate uroliths. There are 2 oxalate preventative diets available that have published data: Prescription Diet u/d and Royal Canin s/o. In a controlled prospective clinical study, dogs consuming Prescription Diet u/d had a 50% reduction in recurrence rates Urine Heaven Page 3
when compared to dogs that were fed a maintenance adult dog food. Royal Canin s/o has been shown to decrease urinary saturation with calcium oxalate; however, long term recurrence studies have not been performed. These diets contain less calcium and are more alkalinizing than maintenance adult dog foods. The other dietary strategy is to feed a high fiber diet and administer supplemental potassium citrate (initial dose: 75 mg/kg PO q12hr). Although no controlled studies exist, this strategy is associated with decreased recurrence rate for calcium oxalate and is useful in dogs that cannot tolerate the higher fat content of the oxalate preventative diets. In cats, there are four diets that are formulated and marketed for prevention of calcium oxalate uroliths in cats including: Hill s Prescription Diet c/d MultiCare, Royal Canin s/o, Purina UR st/ox, and Eukanuba ph/o. These diets contain potassium citrate (as an alkalinizing agent and as a source of citrate) and induce a urine ph of over 6.5. None have been tested long term in cats that form calcium oxalate uroliths; however, consumption of x/d (Hill s Pet Nutrition Inc) and S/O ph Control Formula (Waltham) results in low urine saturation with calcium oxalate. We have had success in reducing mild hypercalcemia in some oxalate urolith-forming cats by feeding Prescription diet w/d (Hill s Pet Nutrition Inc, Topeka, KS) and administering potassium citrate (75 mg/kg PO q12hr adjust to urine ph of 7.5). Purines Urate: Ammonium urate is the third most common mineral found in uroliths in dogs and cats. These uroliths form because of liver disease (usually a portosystemic vascular shunt) or because of an inborn error of metabolism resulting in hyperuricosuria (e. g. Dalmatians and English bulldogs). They are more common in dogs and cats less than 5 years of age. In Dalmatians, urate uroliths are more common in males than females. Ammonium urate uroliths may be dissolved in dogs; however, the success rate is variable. In one study, medical dissolution was effective in approximately 40% of the cases, partial dissolution occurred in approximately 30% of the cases, and no dissolution of growth of uroliths due to xanthine formation occurred in approximately 30% of the cases. We have not had success in dissolving ammonium urate uroliths in dogs with portosystemic vascular shunts. Although no studies have been performed evaluating the efficacy or safety of medical dissolution of urate uroliths in cats with idiopathic urate urolithiasis, we have successfully dissolved urate uroliths in cats using a low protein diet (Prescription Diet k/d, Hill s Pet Products) and allopurinol (7.5 mg/kg PO q12hr). Until further studies are performed to confirm the safety and efficacy of medical dissolution, surgical removal remains the treatment of choice for urate uroliths in cats. Prevention of urate urolith recurrence in cats has been > 90% when using a protein restricted, alkalinizing diet (Prescription Diet k/d, Hill s Pet Products). Laser lithotripsy: For bladder and urethral stones, laser lithotripsy can be performed. This procedure involves anesthetizing the dog or cat and passing a cystoscope. A laser fiber is then introduced through the operating channel of the cystoscope and the stone is broken down into smaller fragments. The fragments and smaller stones are retrieved using a basket retrieval instrument or by voiding urohydropropulsion. The procedure can be done in male dogs, but not male cats, and is more successful in female dogs and cats because the stone must be broken down into fragments that can be retrieved through the urethra, which is easier to do in female animals. For more information or if you have a case, please contact Dr. Joe Bartges or Miss Shanna Hillsman at 865-974-8387. Urine Heaven Page 4
University of Tennessee College of Veterinary Medicine Laser Lithotripsy What is a LASER? A LASER (an acronym for Light Amplification by Stimulated Emission of Radiation) emits light that is not visible to the human eye containing energy that can cut tissue and break up urinary bladder stones. At The University of Tennessee, we use a holmium:yag LASER. LASER treatment is done by anesthetizing the dog or cat and inserting a cystoscope through the urethra into the urinary bladder. The stone or stones can be seen through the cystoscope. A LASER fiber is then passed through the cystoscope and used to shatter the larger stones into smaller pieces that can be removed without surgery. LASER lithotripsy can be done on bladder or urethral stones. How safe is LASER lithotripsy? LASER lithotripsy is very safe. Complications occur in < 10% of procedures and are related to swelling from passing the scope. Potential complications include damage to the lining of the bladder or urethra and urinary tract infections. No long-term complications have been reported. Who can undergo LASER lithotripsy? Eligibility: 1. Female cats and dogs greater than approximately 5 lbs. 2. Male dogs must be able to have 5 French catheter passed (> 12-15 lbs.) 3. Male dogs, small female dogs, and male cats can have lithotripsy performed by cystoscopic-assisted miniapproach cystotomy What is required to perform LASER lithotripsy? Workup Checklist: 1. Abdominal radiographs taken within a month or two 2. CBC, blood work, and urinalysis performed no later than 2-4 weeks prior to procedure; a urine culture is recommended 3. The patient should be fasted (no food) after 10 pm the night before the day of procedure; water can be given. LASER Lithotripsy candidates can be done as day cases if lab work and radiographs have been performed, mailed to UTCVM, and the dog or cat is approved as eligible prior to appointment day. Owners must bring pets in by 9 AM if procedure is to be done as day patient. Pets usually can go home by 5 PM; however, this is not guaranteed and is dependent on how busy the hospital is that day and how well the dog or cat recovers from the procedure. Please mail radiographs and bloodwork to: Attention : Shanna Hillsman LVMT College of Veterinary Medicine, The University of Tennessee 2407 River Drive Knoxville TN 37996-4544 8 year old, F/S, Shih tzu Procedure took 20 minutes > 1cm bladder stone LASER fiber against stone Green light is aiming beam Stone fragmented Stone fragments retrieved by voiding urohydropropulsion Urine Heaven Page 5
Bacterial Urinary Tract Infections A bacterial urinary tract infection (UTI) exists when bacteria adhere, multiply, and persist in a portion of the urinary tract. The infection may or may not produce clinical signs. Bacterial urinary tract infections are reported to occur in 2-3% of dogs and in less than 1% of cats. Cats appear to be innately resistant to bacterial UTI. The urinary tract is in contact with the external environment and has many defense mechanisms to prevent bacterial UTI. Anatomically, the length of the urethra, presence of high pressure zones within the urethra, urethral and ureteral peristalsis, vesicoureteral flaps to prevent reflux of urine from the bladder into the ureters, and extensive renal blood supply and flow are protective. Mucosal defense barriers that prevent migration of bacteria and subsequent colonization include the presence of a glycosaminoglycan layer, antibodies, intrinsic mucosal antimicrobial properties, exfoliation of cells, and bacterial interference by commensal microbes of the distal urethra and distal genital tract. The composition of the urine also aids in prevention of development of bacterial urinary tract infection. Urine produced by cats is normally concentrated, oftentimes having a specific gravity > 1.045 with an associated high osmolality. Urine also contains substances that are inhibitory to bacterial colonization including high urea concentration, and presence of organic acids, low-molecular weight carbohydrates, and Tamm-Horsfall mucoprotein. Cell-mediated and humoral-mediated immunity present within the urine or urinary tract also impart protection. Frequent and complete voiding also helps to wash out bacteria that have migrated into the bladder, ureters, and kidneys. PHYSICAL EXAMINATION FINDINGS AND CLINICAL SIGNS Clinically, bacterial urinary tract infections may be symptomatic or asymptomatic. Bacterial infection of the lower urinary tract is usually associated with clinical signs that are similar to other diseases of the lower urinary tract. These signs include, but are not limited to, pollakiuria, dysuria, stranguria, hematuria, and inappropriate urination. Bacterial urinary tract infection of the kidneys may be associated with hematuria, or if septicemia develops, the animal may be systemically ill. In addition, upper urinary tract infections may cause recurrent lower urinary tract infections. DIAGNOSIS Urinalysis and Urine Culture Evaluating results of a complete urinalysis of a sample collected by cystocentesis is the best way to screen for bacterial UTI. Some dipsticks contain reagent pads for nitrate or leukocyte esterase activity; however, these pads are not reliable for ruling-in or ruling-out bacterial UTI in dogs and cats. A urine sediment examination should always be performed as part of a complete urinalysis. Presence of pyuria (> 5 white blood cells / high-powered field) is important because other causes of lower urinary tract disease are associated with hematuria and proteinuria but minimal pyuria. Identification of bacteria on urine sediment examination is helpful; however, it should not be relied upon to rule-in or rule-out bacterial UTI. Evaluating a modified Wright s stain urine sediment preparation is a cost-effective and easy method that provides more reproducible and accurate results than evaluating an unstained urine sediment preparation. Urine specific gravity may be normal; however, dilute urine may be a risk factor for development of bacterial UTI or a consequence of an upper urinary tract infection. A urine culture is the most definitive means of diagnosing bacterial UTI. Care must be taken to collect, preserve, and transport the urine sample to avoid contamination, or proliferation or death of bacteria. Urine specimens for aerobic bacterial culture should be transported and stored in sealed, sterilized containers, and processing should begin as soon as possible. If laboratory processing is delayed by more than 30 minutes, the specimen should be refrigerated (4 C). Blood agar plates may be inoculated and incubated for 24 hours. If bacteria are present on the plate after 24 hours, the plate may be submitted for identification and determination of antibiotic sensitivities. The most common technique used for determining antimicrobial susceptibility is the Kirby-Bauer agar diffusion test. After an organism is isolated, it is streaked on an agar plate and antimicrobial discs are placed on the plate. This test is based on attainable antimicrobial concentrations in human plasma and the assumption is that plasma concentrations are similar between species. However, many antibiotics attain higher concentrations in urine than in plasma; therefore, this technique may underestimate a microbe s susceptibility to antimicrobials. A more sensitive and specific technique is to determine the minimum inhibitory concentration (MIC). The MIC is the lowest concentration of antimicrobial required to inhibit bacterial growth. It is performed using a series of dilutions of each antibiotic in a multi-well plate to which a standard number of bacteria are added. Although this is a better test, it is more expensive and for most bacterial isolates, the Kirby-Bauer method is acceptable. Urine Heaven Page 6
Bacteria that commonly cause UTI are the same in dogs and cats. Infections caused by Escherichia coli are the most common, accounting for one-third to one-half of all organisms isolated from the urine of infected animals. Gram-positive cocci are the second major group of organisms. Staphylococci and streptococci account for onefourth to one-third of the isolates recovered. Bacteria that cause the remaining one-fourth to one-third of urinary tract infections include Proteus spp., Klebsiella spp., Pasteurella spp., Enterobacter spp., Pseudomonas spp., Corynebacterium spp., and Mycoplasma spp.; however, these are uncommon. Unless septicemia is present, results of a CBC should be normal. If septicemia is present, leukocytosis and a left shift may be present. Bacterial infection of the lower urinary tract does not cause changes in serum biochemical analysis. In animals with pyelonephritis, serum biochemical analysis may be normal if only one kidney is infected or if minimal damage has occurred, or it may reveal biochemical changes consistent with renal failure. Hyperthyroidism has also been associated with inducing a diuresis and bacterial urinary tract infections in cats. Additional laboratory evaluation of cats may include testing for Feline Leukemia Virus and Feline Immunodeficiency Virus, which may compromise the immune system. Radiography, Ultrasonography, and Endoscopy In many animals with bacterial urinary tract infections, radiography will be normal. However, survey radiography may reveal uroliths, renomegaly, or other defects that may predispose to development of bacterial urinary tract infection. If no abnormalities are found by survey abdominal radiography, ultrasonography or contrast radiography should be performed. The upper urinary tract may be evaluated by use of excretory urography; whereas, the lower urinary tract may be evaluated by use of contrast cystography and urethrography, and double contrast cystography. A disadvantage of performing contrast radiography of the lower urinary tract is risk of inducing bacterial urinary tract infections during catheterization. Ultrasonography is a non-invasive technique and can evaluate the kidneys and bladder; however, its use is limited for evaluating the ureters and majority of the urethra. Endoscopy of the lower urinary tract may be useful in identifying mucosal and intra-luminal lesions of the urinary tract, which may predispose to bacterial infection. In one study, a urolith not visible by survey radiography was visualized during cystoscopy. Disadvantages of cystourethroscopy include requiring anesthesia to perform the procedure, invasion of the lower urinary tract which may compromise host defense mechanisms, and difficulty of performing the procedure in male cats without perineal urethrostomies. TREATMENT Treatment of bacterial UTI is dependent upon whether the infection occurs due to a temporary breech in the body s defense mechanisms (uncomplicated) or whether there is an irreversible breech in the defense mechanisms (complicated). Eradication of bacterial urinary tract infection is dependent on selection of the appropriate antibiotic, administering it at the proper dosage and duration, and appropriate follow-up. Uncomplicated bacterial UTI Uncomplicated bacterial UTI are those where no underlying structural, neurologic, or functional abnormality is identified. Uncomplicated bacterial UTI are usually successfully treated with a 10-14 day course of an appropriate antimicrobial agent. If the proper antibiotic is chosen and administered at the appropriate dosage and frequency, clinical signs should resolve within 48 hours. Additionally, results of a complete urinalysis should improve within this same time frame. If possible, a urine culture should be performed 5-7 days after cessation of antimicrobial therapy in order to ensure eradication of the UTI. Complicated bacterial UTI Reproductively intact dogs, all cats, and animals with identifiable predisposing causes for bacterial UTI (e.g. renal failure, hyperadrenocorticism, diabetes mellitus, etc) should be considered to have a complicated bacterial UTI. Pyelonephritis and prostatitis are examples of complicated bacterial UTI. When a cat is confirmed with a bacterial UTI, they should be treated as a complicated UTI because cats are inherently resistant to development of an infection. Treatment with antibiotics for longer than the routine 10 to 14 days may be indicated, and are usually administered for 4-6 weeks. Urine should be evaluated in the first week of treatment for response to therapy and prior to discontinuing therapy. After antimicrobial therapy is discontinued, urine should be cultured 5-7 days later. Use of once a day antibiotic treatment may be necessary in order to control bacterial urinary tract infections that are difficult to eradicate. Urine Heaven Page 7
Recurrence of bacterial UTI Relapse A relapse is defined as recurrence of a bacterial UTI due to the same organism. Relapses usually occur within days to weeks of discontinuing antimicrobial therapy. Possible causes of relapse include use of an inappropriate antimicrobial agent, administering an appropriate antimicrobial agent at the inappropriate dosage, frequency, or duration, or complicating factors. A urine culture should be evaluated prior to re-instituting antimicrobial therapy. Additionally, further diagnostic evaluation may be warranted. Reinfection A reinfection is defined as an infection with a different organism than what was initially present. Reinfections usually occur weeks to years after cessation of antimicrobial therapy. Although predisposing risk factors may be present, many animals that become reinfected often do not have identifiable risk factors. If reinfections are infrequent, each episode may be treated as an uncomplicated bacterial UTI. However, if reinfections occur at a frequency of >3 per year, then animals should be treated as having a complicated bacterial UTI. Additionally, prophylactic antimicrobial therapy may be warranted. Superinfections A superinfection occurs when a second bacterial organism is isolated while an animal is receiving antimicrobial therapy. Oftentimes, this organism displays a high degree of antibiotic resistance. A bacterial UTI that occurs in animals receiving antimicrobial therapy that also have an indwelling urethral catheter is an example of a superinfection. PREVENTION Bacterial UTI can be prevented by minimizing bacterial contamination of the urinary tract and by avoiding or minimizing conditions that impair host defenses. Catheterization and endoscopy of the urinary tract always carry a risk of inducing an infection. The magnitude of the risk increases with the degree of pre-existing urinary tract abnormality, the amount of any additional injury caused by the procedure, and the duration of the procedure. These risks of infection can be minimized by being careful to perform invasive procedures only when necessary, by performing the procedure as atraumatically as possible, and by removing the catheter or endoscope as soon as possible. Cats with perineal urethrostomies are also at higher risk for developing bacterial urinary tract infections compared with cats without perineal urethrostomies; thus, other therapeutic interventions should be tried before resorting to this procedure. Catheter-induced bacterial UTI present a common problem encountered by veterinarians. Bacteria may migrate along the outside of the catheter or through the lumen. Risk of bacterial UTI increases with pre-existing urinary tract disease or urothelial damage. The risk is greater in animals with indwelling urethral catheters when compared with animals that are intermittently catheterized. 11 Despite this lower risk, one study documented bacterial UTI in 7 of 35 dogs that were catheterized one time. Bacterial UTI occurs in >50% of animals after 4 days of an indwelling urethral catheter. Antibiotic therapy while an indwelling catheter is in place decreases the frequency of bacterial UTI; however, when bacterial UTI occur, the organisms exhibit a greater degree of antimicrobial resistance. Catheter-associated bacterial UTI may be minimized by using intermittent catheterization when possible, removing indwelling catheters as soon as possible, using a closed collection system, and avoiding administering antimicrobial agents while urethral catheters are inserted. Prophylactic antimicrobial therapy may be indicated in animals with relapses or frequent reinfections. The antimicrobial agent should be selected based on urine bacterial culture and susceptibility testing. The agent is administered at ½ to 1 / 3 of the daily therapeutic dose, and is usually administered once a day at night. Urine should be re-cultured every 4-6 weeks to insure control of the bacterial UTI. Experience has shown that if animal does not have a break-through infection during a 6-month period, then antimicrobial therapy may be successfully discontinued. Disadvantages of this approach include development of resistant bacteria and side effects of the antimicrobial agent. An alternative to prophylactic antimicrobial therapy in dogs is administration of methenamine. Methenamine is a urinary tract antiseptic that is effective when the urine ph is less than 6.0. It is used for prophylaxis and requires a sterile urine culture prior to use. Because it requires an acidic urine ph, it is contraindicated in dogs with metabolic diseases associated with metabolic acidosis (e.g. chronic renal failure and diabetic ketoacidosis); cats do not tolerate methenamine as well as dogs. In addition, methenamine will not be effective with bacterial UTI that involve urease-producing microbes that are associated with alkaluria. Urine Heaven Page 8
Algorithm for diagnosis and management of bacterial UTI in dogs and cats Intact male or female dog? Predisposing systemic and/or local factor(s)? Recent previous UTI s? Cat? YES NO Treat for 4-6 weeks based on C & S Redo C & S - 5-7 days after start - Before stop - 5-10 days after start Treat for 10-14 days based on: C & S Best guess Urinary Incontinence Micturition is the physiologic process of storage and complete voiding of urine. Disorders of micturition can be divided according to the phase of micturition affected (disorders of voiding, disorders of storage), pathophysiology (neurogenic, non-neurogenic), frequency (continuous, intermittent), and residual urine volume (distended urinary bladder, non-distended urinary bladder). Incontinence is the involuntary passage of urine. The most useful classification of urinary incontinence is based on the functional status of the urinary pump (bladder) and outlet (bladder neck and urethra). A hypocontractile bladder is found with detrusor atony where animals are unable to generate sufficient intravesicular pressure to initiate or to complete voiding. A hypercontractile bladder is found with urge incontinence where normal filling and storage of urine in the bladder is lost owing to inappropriate neurologic signals, changes in bladder compliance or capacity, or idiopathic causes (Table 1). Pharmacological agents used to treat various causes of micturition disorders are presented in Table 2. Urine Heaven Page 9
Table 1. Major types of micturition disorders of small animals. Disorder Neurogenic disorders of micturition Sacral spinal cord/peripheral nerve lesions Suprasacral spinal cord lesions Brain stem lesions Cerebellar lesions Non-neurogenic disorders of micturition Congenital or anatomic abnormalities Ectopic ureter(s) Patent urachus Acquired disorders characterized by increased residual volumes Bladder hypocontractility due to overdistention Increased urethral resistance Physical obstruction Functional urethral obstruction Detrusor-urethral dyssynergia Acquired disorders characterized by normal residual volumes Urinary bladder hypercontractility due to UTI, neoplastic infiltration or mass, or idiopathic causes Urethral hypotonicity Reproductive hormone responsive Congenital UTI Prostatic disease Characteristics Distended, flaccid urinary bladder, easily expressed; depressed genitoanal reflexes; weak or absent voiding efforts Distended, often firm urinary bladder, not easily expressed; weak or incomplete voiding efforts with time; proprioceptive deficits Distended urinary bladder; interrupted voiding pattern; cranial nerve or gait deficits Inappropriate voluntary voiding; pollakiuria, nocturia; ataxia, intention tremors Continuous or severe intermittent incontinence since birth Urine dribbling from urachus Distended urinary bladder; intermittent overflow incontinence; absent or incomplete voiding Distended urinary bladder; dysuria with little or no urine voided; intermittent overflow incontinence if partial obstruction Same as physical obstruction Distended urinary bladder, dysuric or interrupted voiding patterns Small urinary bladder; intermittent urine leakage; may leak urine when active; possible UTI or FeLV infection Small urinary bladder; voiding pattern normal; intermittent urinary incontinence, often when animal is recumbent DISORDERS OF MICTURITION The prevalence of urinary incontinence increased dramatically in both male and female dogs over 7 years of age; most dogs were neutered. Collection of detailed historical information is helpful in determining if incontinence is present and potential causes. Physical examination should include a rectal examination in male and female dogs, and a complete neurological examination should be performed. If possible, observance of micturition is beneficial; however, it is often impossible in a hospital setting. A urinalysis and urine culture should be included in the minimum database for incontinence. Radiography, ultrasonography, urodynamic assessment, and cystoscopy may be indicated. Disorders leading to urinary retention (distended bladder) Urine retention is caused by failure of detrusor contraction, increased outflow resistance, or both. NEUROGENIC DISORDERS Upper motor neuron lesions (cranial to sacral spinal cord segments) and lower motor neuron lesions (sacral spinal cord segments or bilateral peripheral nerves) may result in urine retention. With upper motor neuron disorders, the urinary bladder is difficult to express; whereas, in lower motor neuron disorders, the bladder is easy to express. Reflex dyssynergia is a loss of coordination between bladder contraction and urethral relaxation characterized by normal initiation of urination with abrupt termination of urine stream and incomplete voiding. Treatment involves pharmacologic relaxation of urethra and stimulation of bladder contraction (Table 2). NON-NEUROGENIC DISORDERS Urine retention occurs because of detrusor atony or hypocontractility or increased outflow obstruction due to a mechanical cause(s). Disorders leading to urinary incontinence (bladder not distended) Incontinence is typically characterized by intermittent leakage of small amount of urine occurring while the animal is relaxed or asleep. It is caused by increased detrusor contractility or, more commonly, decreased urethral tone. BLADDER HYPERCONTRACTILITY Bladder hypercontractility may be caused by sensory disorders (inflammation, neoplasia) and chronic partial outflow obstruction. Treatment involves relaxing the urinary bladder and facilitating normal micturition. Urine Heaven Page 10
URETHRAL DYSFUNCTION (Urethral incompetence) Urethral sphincter mechanism incompetence responsive to sex-hormone replacement is the most common implicating cause for urine leakage in older female dogs; however, other factors are thought to be important. In human beings, it has been hypothesized that age-related changes that occur in the urinary tract (decline in urethral closure pressure, reduction in the urethral length of females, increased post-voiding residual volume), could not cause incontinence by themselves, but predispose to urine leakage. Changes in fluid excretion are considered as equally important risk factors, and the onset of urinary incontinence often coincides with development of polyuria. Therefore, in addition to medications that increase urethral tone (Table 2), therapy to minimize excess fluid excretion (e.g. low solute diets such as those designed for use with renal failure), avoiding high solute treats, and management of the polyuric condition (e.g. hyperadrenocorticism) should also be considered for control of urinary incontinence in dogs. The diagnosis of urethral sphincter mechanism incompetence requires urethral pressure profilometry, which is available in a few referral practices. However, historical and physical examination findings are often enough to make the diagnosis. Many animals respond to DES or another conjugated estrogen (Table 2). Phenylpropanolamine is more efficacious, but must be administered several times during the day. Find and use the lowest possible dose to control incontinence. In older female dogs, the onset of incontinence is also related to a polyuric state, as stated above; therefore, evaluation of diseases or medications associated with polyuria should be investigated. If no specific disease can be found, then use of a low solute diet (such as one designed for use with chronic renal failure) may aid in decreasing polyuria, which may be of benefit with incontinence. Another cause of incontinence in older dogs is lumbosacral disease. A good neurologic examination and possibly abdominal radiography may aid in the diagnosis of lumbosacral disease. Surgical correction of a disk or stenosis at that area may be necessary; myelography, epidurography, or CT scan or MRI may be necessary to diagnose this condition. Lastly, incontinence may be worsened by a concomitant UTI; therefore, a complete urinalysis with possible culture and sensitivity should be performed in all dogs and cats with incontinence. If dogs fail medical therapy, alternative therapy utilizing urethral sub-mucosal injections of collagen or extracellular matrix or surgery such as colposuspension should be considered. Collagen injections for urethral bulking has become available at a reasonable cost; however, it requires being able to perform cystoscopy and cannot be done in male dogs or cats cystoscopically. In a study of 40 dogs, collagen injection resulted in 27/40 (68%) of dogs becoming completely continent, 10/40 (25%) improving in their clinical signs with 6 of these dogs achieving continence with medical therapy, and 3/40 (7%) not responding. Average length of continence was 18 months; however, some dogs were continent for 4 to 5 years. These results are similar to those observed in humans. Collagen injections can be repeated. We are performing collagen injections for urinary incontinence and have done more than 20 cases. Most animals are continent for more than 12 months, and our longest length of continence (to date) is over 30 months without additional medication. In animals with urinary incontinence secondary to an ectopic ureter, the ureter should be repaired. There are basically 2 types of ectopic ureters: (1) simple where the ureter bypasses the trigone and empties directly into the urethra or vagina and (2) tunneling where the ureter attaches at the trigone, but tunnels down the wall of the urethra before opening. Simple ectopic ureters can be repaired surgically by transaction and implantation into the urinary bladder with high success of continence. Although tunneling ectopic ureters can be repaired in a similar fashion, many dogs are incontinent. A newer technique involves laser resection of the ectopic ureter, and is associated with a high rate of continence. Urine Heaven Page 11
Table 2. Pharmacological agents used in management of micturition disorders in dogs (D) and cats (C). Agent Mechanism of action Recommended dosage Adverse effects Agents used to increase urinary bladder contractility Bethanechol Parasympathomimetic; direct cholinergic activity Agents used to decrease urinary bladder contractility Propantheline Parasympatholytic; acetylcholine blockade Oxybutynin Parasympatholytic; antispasmodic; detrusor relaxation D: 5-25 mg PO q8h C: 1.25-7.5 mg PO q8h D: 7.5-30 mg PO q8h C: 5-7.5 mg PO q8h or 7.5 mg PO q72h D: 1.25-5 mg PO q8-12h C: 0.5-1.25 mg PO q8-12h Nausea, vomiting, salivation Nausea, vomiting, constipation, sedation, increased ocular pressure Nausea, vomiting, urine retention, diarrhea, sedation Flavoxate Direct smooth-muscle relaxant D: 100-200 mg PO q6-8h Weakness Dicyclomine Anti-muscarinic D: 10 mg PO q6-8h Nausea, vomiting, constipation, sedation, increased ocular pressure Imipramine Tricyclic antidepressant with anticholinergic, alpha-and betaagonist effects, detrusor smooth muscle relaxation and urethral muscle contraction D: 5-15 mg PO q12h C: 2.5-5 mg PO q12h Agents used to increase urethral resistance DES Reproductive hormone D (females): 0.1-1 mg PO q24h for 5 days (approximately 0.2 mg/kg) followed by 0.1-1 mg PO q7d Estriol (Incurin) Reproductive hormone D: 0.5-2 mg PO q24h initially; followed by 0.5-2 mg PO q2-3d Premarin Reproductive hormone D: 20 mcg/kg q24hr x 7-10d; then q1-3d Testosterone propionate Reproductive hormone D (males): 2.2 mg/kg SQ or IM q2-3d C (males): 5-10 mg IM as needed Testosterone cypionate D (males): 2.2 mg/kg IM q30d or 200 mg Phenylpropanolamine Ephedrine Alpha agonist; urethral smooth muscle contraction Alpha agonist; urethral smooth muscle contraction Agents used to decrease urethral resistance Phenoxybenzamine Alpha antagonist; urethral smooth muscle relaxation IM q30 d D: 12.5-50 mg PO q8h; 1-2 mg/kg PO q8h C: 1.0-1.5 mg/kg PO q8h D: 1.2 mg/kg PO q8h or 5-15 mg PO q8h C: 2-4 mg/kg PO q6-12h or 2-4 mg PO q8h D: 5-15 mg PO q12h C: 2.5-10 mg PO q24h D, C: 0.25 mg/kg PO q12h Seizures, tremors, tachycardia, hyperexcitability Signs of estrus, bone marrow suppression Aggression, prostatic disease, perineal hernia Anxiety, cardiac arrhythmias, anorexia, hypertension Anxiety, cardiac arrhythmias, hypertension Hypotension, tachycardia, vomiting, diarrhea, increased intraocular pressure Prazosin Alpha antagonist; urethral smooth D, C: 1 mg/15kg PO q12-24hr Hypotension muscle relaxation Terazosin Alpha antagonist; urethral smooth D, C: 0.5-5 mg PO q12-24hr Hypotension muscle relaxation Diazepam Striated muscle relaxation; central nervous system depressive D: 0.2 mg/kg PO q8h or 2-10 mg PO q8h C: 2.5-5 mg PO q8h or as needed or 0.5 Sedation, paradoxical excitement effect mg/kg IV Aminopromazine Smooth muscle relaxation D, C: 2.2 mg/kg PO q12h Acepromazine Urethral muscle relaxation by neuroleptic effect; alpha antagonism C: 0.1 mg/kg IV or 1.1-2.2 mg/kg PO Sedation, hypotension, seizures Dantrolene Nicergoline Striated muscle relaxation; direct action Alpha antagonism; urethral smooth muscle relaxation D: 3-15 mg/kg PO q24h divided or 0.5-1 mg/kg PO q8h C: 0.5-1 mg/kg PO q12h D, C: 1-5 mg PO q8h Weakness, hepatotoxicity Urine Heaven Page 12
University of Tennessee College of Veterinary Medicine Collagen Injections for Urinary Incontinence What is urinary incontinence? Urinary incontinence refers to leaving puddles of urine where a dog or cat sleeps. During the day, the dog or cat can hold their urine and urinate normally; however, when they relax or fall asleep, urine leaks out. Most commonly, this occurs in older spayed female dogs and is often referred to as spay incontinence, hormonallyresponsive incontinence, or urethral sphincter mechanism incompetency (USMI). In male and female cats and in male dogs, usually there is a more serious underlying cause for the urinary incontinence. There are several treatments available for urinary incontinence. Medically, estrogen or phenylpropanolamine can be used individually or together in spayed female dogs, and 50-85% respond. For those that do not respond, there are surgical procedures that can be tried; however, complication rates are high and restoring continence is low. How do collagen injections work for urinary incontinence? Collagen (glutaraldehyde cross-linked bovine collagen) is a substance that is injected under the lining of the urethra just beyond where it connects to the urinary bladder. Collagen bulks the area increasing the pressure at this part of the urethra, which is important for urinary continence. Additionally, collagen stimulates new blood vessel growth into the area and some scar tissue formation. Collagen injections provide over 90% success rate with an average of 18 months of continence; dogs are usually continent within a couple of days of the procedure. It is not a permanent cure; however, some dogs can be continent for up to 5 years with 1 treatment. Reported response rates to collagen injections in dogs are 65% continence at 18 months, 38% continence with medication, and 7% experiencing no benefit. Collagen injections can be repeated, if necessary. Collagen injections are safe and reported complications include irritation from performing cystoscopy, possible urinary tract infections, and lack of response to the injections. Who can undergo collagen injections for urinary incontinence? Eligibility: 1. Female cats and dogs greater than approximately 5 lbs. that have failed medical treatment for urinary incontinence, that do not have other serious health issues, and that do not have a urinary tract infection What is required to perform collagen injections for urinary incontinence? Workup Checklist: 1. Abdominal radiographs taken within the last 3 months 2. CBC, blood work, and urinalysis performed no later than 2-4 weeks prior to procedure; a urine culture is recommended 3. The patient should be fasted (no food) after 10 pm the night before the day of procedure; water can be given. 8 year old, F/S, border collie Procedure took 20 minutes Proximal urethra prior to injection Injection needle inserted First injection of collagen Proximal urethra after additional injections Urine Heaven Page 13
University of Tennessee College of Veterinary Medicine Laser Treatment for Ectopic Ureter What is a LASER? A LASER (an acronym for Light Amplification by Stimulated Emission of Radiation) emits light that is not visible to the human eye containing energy that can cut tissue and break up urinary bladder stones. At The University of Tennessee, we use a holmium:yag LASER. The ureters are the tubes that connect the kidneys to the bladder. Normally, they enter at the junction of the urinary bladder and the urethra (the outflow tube from the bladder for passing urine). An ectopic ureter is a ureter that does not enter at the trigone. There are 2 types of ectopic ureters: (1) simple ectopic ureter: this occurs when the ureter bypasses the urinary bladder and connects to the urethra or vagina, and (2) tunneling ectopic ureter: this occurs when the ureter enters the bladder at the trigone, but tunnels down the wall of the urethra before opening up. An ectopic ureter occurs due to a congenital defect, meaning the dog or cat was born with the abnormality. Dogs and cats with ectopic ureters often dribble urine continuously, are difficult to house train, and experience recurrent urinary tract infections. Treatment involves re-establishing normal anatomy. Surgery can be done to tie off the ectopic ureter and re-implant the ureter back into the bladder. This works extremely well with a simple ectopic ureter; however, it does not work as well with a tunneling ectopic ureter because many animals still have urinary incontinence. LASER treatment works well with a tunneling ectopic ureter. LASER treatment is done by anesthetizing the dog or cat and inserting a cystoscope through the urethra into the urinary bladder. A LASER fiber is then passed through the cystoscope and used to cut back the ridge of excess tissue so that the ectopic ureter now empties into the urinary bladder. How safe is LASER treatment for a tunneling ectopic ureter? LASER treatment is very safe. Complications occur in < 10% of procedures and are related to swelling from passing the scope. Potential complications include damage to the lining of the bladder or urethra and urinary tract infections. Most dogs and cats do not leak urine after this procedure, but that could occur. Who can undergo LASER treatment for a tunneling ectopic ureter? Eligibility: 2. Female cats and dogs greater than approximately 5 lbs. What is required to perform LASER treatment for a tunneling ectopic ureter? Workup Checklist: 1. Abdominal radiographs and ultrasound 2. CBC, blood work, and urinalysis performed no later than 2-4 weeks prior to procedure; a urine culture is recommended 3. The patient should be fasted (no food) after 10 pm the night before the day of procedure; water can be given. Urinary bladder 8 month old, F/S terrierx Procedure took 15 minutes Left ureter Urethra Right ureter (ectopic; tunneling) LASER fiber Catheter in right ureter Right ureter Urine Heaven Page 14