Acquired Disorders of the Urinary Tract

By | November 29, 2015

Renal Dysfunction

In our experience, acquired disorders are the most common cause of renal dysfunction in puppies and kittens. Causes of acquired renal dysfunction in immature animals are similar to those encountered in adults and may include infectious, inflammatory, toxic, ischemic, or neoplastic disease processes.

GLOMERULOPATHIES

Like their familial and congenital counterparts, acquired glomerulopathies are characterized by morphologic and/or functional alteration of glomeruli that, if progressive, may induce subsequent changes in renal tubules, interstitium, and blood vessels resulting in chronic generalized renal dysfunction (). Acquired glomerulopathies usually develop secondary to systemic disorders in which the underlying disease processes damage not only the glomeruli but other major organs as well. Acquired glomerulopathies are infrequently encountered in young dogs and cats (). Diagnosis is based on clinical and laboratory evaluations similar to those described for familial glomerulopathies. Unlike familial disease, however, glomerulopathies acquired secondary to systemic disorders are potentially reversible. Identification and elimination of the primary disease process may halt progression of glomerular injury and, in some cases, result in its remission.

ACUTE TUBULAR NECROSIS

Acute tubular necrosis (acute intrinsic renal failure, nephrosis, vasomotor nephropathy) is a syndrome characterized by abrupt and sustained reductions in glomerular filtration rate associated with acute tubular degeneration (). Acute tubular necrosis is believed to result from a combination of vascular and tubular effects induced by renal hypoperfusion (ischemia) or nephrotoxins. Acute tubular necrosis is a common cause of acquired renal dysfunction in young dogs and cats (). Any condition predisposing to persistent or severe hypotension, hypovolemia, circulatory collapse, or renal hypoperfusion may induce acute tubular necrosis and renal failure (). We observed ischemia-induced acute tubular necrosis in a 7-day-old beagle puppy associated with respiratory arrest after aspiration of food. More commonly, acute tubular necrosis is associated with exposure to nephrotoxins (i.e., ethylene glycol; antimicrobial agents; radiographic contrast agents; heavy metals such as arsenic, mercury, lead, and zinc; plants such as Easter lily; herbicides; and nonsteroidal antiinflammatory drugs such as ibuprofen, phenylbutazone, and acetaminophen) (). Analgesic-induced acute renal failure was observed in two kittens after administration of a single dose of 25 to 50 mg of ibuprofen. Both kittens recovered after symptomatic and supportive care.

Clinical signs associated with acute tubular necrosis are variable and depend on the degree of renal parenchymal damage and extent of multisystem involvement. Mild nephrotoxic or ischemic renal injury is often self-limiting, and animals may be asymptomatic. Transient proteinuria, hematuria, pyuria, and abnormal number of casts may be observed in urine sediment. In moderate to severe acute tubular necrosis, clinical signs characteristic of acute oliguric or nonoliguric renal failure and uremia are usually present. A diagnosis of toxic or ischemic acute tubular necrosis is based on history, physical examination, and laboratory findings. Treatment of acute tubular necrosis should be designed to eliminate or correct the specific cause if it is known. In cases of moderate to severe injury associated with acute renal failure, symptomatic and supportive therapy designed to minimize abnormalities in fluid, electrolyte, acid-base, and nutritional balance may allow life to be sustained until the body can restore adequate renal structure and functions.

TUBULOINTERSTITIAL DISEASES

Renal tubulointerstitial diseases include disorders such as acute generalized nephritis, chronic tubulointerstitial nephropathy, pyelonephritis, and hypercalcemic nephropathy (). In our experience, tubulointerstitial diseases are the most common type of renal disease observed in young dogs and cats (). Acute generalized nephritis refers to acute inflammatory diseases of the kidney that are characterized by interstitial inflammatory cell infiltrates, edema, and focal tubular degeneration (). Acute generalized nephritis may be caused by systemic bacterial infections (e.g., bacterial endocarditis, bacterial septicemia, leptospirosis), systemic viral infection (e.g., canine herpesvirus, feline infectious peritonitis virus), immunologic disorders (e.g., systemic lupus erythematosus), and drugs (e.g., methicillin) (). Systemic bacterial infections and feline infectious peritonitis virus were the most common etiologic agents identified in our series of puppies and kittens with acute nephritis (). Clinical and laboratory abnormalities are indicative of acute renal failure and are indistinguishable from those associated with nephrotoxic or ischemic acute tubular necrosis. Diagnostic and therapeutic efforts should be directed at identifying and eliminating the primary cause in addition to providing supportive therapy for renal failure. Chronic tubulointerstitial nephropathy is characterized by abnormally small, misshapen, irregular kidneys and microscopic findings of interstitial fibrosis, tubular atrophy, and mononuclear cell infiltration of the renal parenchyma (). Kidneys affected by more advanced forms of chronic tubulointerstitial nephropathy are often referred to as “end-stage kidneys.” In many cases, the underlying cause cannot be identified or localized to any particular portion of the nephron. In our experience, chronic tubulointerstitial nephropathy appears to be more common in young dogs than in young cats (). Clinical findings of chronic tubulointerstitial nephropathy depend on the degree of renal injury and the severity of renal dysfunction. Animals with advanced disease usually present with clinical and laboratory findings characteristic of chronic renal failure and uremia and are indistinguishable from those caused by many congenital nephropathies. Histologic evaluation of renal biopsy samples may help differentiate chronic tubulointerstitial nephropathy from congenital forms of renal disease. Treatment is limited to symptomatic and supportive care ().

PYELONEPHRITIS

Pyelonephritis is the consequence of ascending bacterial urinary tract infections (). Congenital or acquired abnormalities of the urinary tract that compromise host defenses may represent important predisposing factors in the pathogenesis of pyelonephritis (Table Host Defense Abnormalities Predisposing Immature Dogs and Cats to Complicating Bacterial Urinary Tract Infections). Urinary stasis or obstruction, vesicoureteral reflux, and anatomic abnormalities of the ureter or vesicoureteral junction are potentially important predisposing factors in young animals (). Pyelonephritis is a major cause of renal disease in young animals, especially puppies. In our series, pyelonephritis was the most common cause of renal disease in dogs younger than 6 months (). In contrast, pyelonephritis was not diagnosed in any kitten during the same period. These observations may reflect the relatively high incidence of vesicoureteral reflux in young dogs and/or less effective host urinary tract defenses in dogs compared with cats. Bacterial infections of the kidney may be acute or chronic and focal or disseminated (). Animals with advanced chronic generalized pyelonephritis typically have small, scarred kidneys, similar in gross appearance to those of animals with advanced chronic tubulointerstitial nephropathy.

Table Host Defense Abnormalities Predisposing Immature Dogs and Cats to Complicating Bacterial Urinary Tract Infections

Altered Anatomic Barriers

  • Congenital
  • Ectopic ureters
  • Ureteroceles
  • Ureteral duplication
  • Urachal anomalies
  • Exstrophy
  • Colocystic fistula
  • Urethrovaginal malformations
  • Ectopic urethra
  • Urethral duplication
  • Urethral hypoplasia
  • Epispadias/hypospadias
  • Acquired
  • Urethrostomy
  • Urethral stricture

Urine Retention

  • Urethral obstruction (partial or complete)
  • Uroliths
  • Urethral matrix-crystalline plugs
  • Urethral stricture
  • Ureterocele
  • Neoplasia
  • Urachal diverticula
  • Detrusor atony or hypotony
  • Spinal trauma
  • Spinal dysraphism
  • Chronic overdistention
  • Dysautonomia

Damage to Urothelium

  • Trauma
  • Palpation
  • Catheterization
  • Lavage
  • Urolithiasis
  • Inflammation
  • Neoplasia

Altered Urine Volume or Composition

  • Decreased urine osmolality
  • Renal failure
  • Nephrogenic diabetes insipitus
  • Postobstructive diuresis
  • Fluid therapy
  • Diuretic administration
  • Urinary bladder lavage
  • Decreased urine volume
  • Negative water balance
  • Decreased water consumption
  • Dehydration
  • Primary oliguric renal failure
  • Glucosuria

Impaired Immune Responsiveness

  • Immunosuppressive drug administration
  • Congenital immunodeficiency
  • Uremia

Clinical findings associated with pyelonephritis depend on the degree of renal involvement and the duration of infection (). Acute generalized pyelonephritis may be associated with varying degrees of pyrexia, lethargy, anorexia, vomiting, renal pain, leukocytosis, bacteriuria, pyuria, and casts. Finding white blood cell casts with bacteriuria is strongly suggestive of bacterial pyelonephritis. Manifestations of chronic generalized pyelonephritis are often subtle but may include polyuria, polydipsia, isosthenuria, recurrent asymptomatic bacteriuria, or recurrent urethrocystitis. If generalized involvement of both kidneys occurs, clinical signs and laboratory findings associated with renal failure may be present. A diagnosis of pyelonephritis is based on history, physical examination, and results of laboratory evaluations (complete blood count, serum biochemistries, urinalysis, quantitative urine culture) and radiographic or ultrasonographic studies. Treatment of bacterial pyelonephritis consists of antimicrobial therapy and the elimination of predisposing factors. Because eradication of bacteria from the kidney may be difficult, antimicrobial therapy is usually continued for 4 to 6 weeks (). In uremic animals, supportive therapy for renal failure should be provided.

Infection

Urinary tract infection (UTI) encompasses a variety of clinical entities whose common denominator is microbial invasion of any or all of its components. Bacteria are the most common uropathogen encountered in puppies and kittens, but urinary tract infection may also result from colonization of the urinary tract by mycoplasmas, ureaplasmas, fungi, viruses, and algae (Table Canine and Feline Uropathogens). An uncomplicated urinary tract infection is one in which no underlying structural, neurologic, or functional abnormality can be identified. Complicated urinary tract infection occurs as a result of microbial invasion of the urinary system secondary to identifiable abnormalities that interfere with normal host defense mechanisms. Review of hospital records at the Michigan State University Veterinary Teaching Hospital revealed that over a 5-year period, urinary tract infections were identified in 15 dogs and 1 cat younger than 6 months.

Table Canine and Feline Uropathogens

Bacteria

Rods and cocci

  • Escherichia coli
  • Staphylococcus spp
  • Streptococcus spp
  • Proteus spp
  • Klebsiella spp
  • Pseudomonas spp
  • Enterobacter spp
  • Pasteurella spp
  • Others

Spirochetes

  • Leptospira interrogans

Rickettsia

  • Ehrlichia cants*
  • Rickettsia rickettsii*

Mycoplasmas

  • Mycoplasma spp*
  • Ureaplasma spp*

Algae

  • Prototheca spp*

Fungi

  • Candida spp
  • Torulopsis*
  • Histoplasma
  • Blastomyces*
  • Cryptococcus
  • Coccidioides*
  • Aspergillus spp
  • Trichosporon sppt
  • Cephalosporiumi

Viruses

  • Canine adenovirus 1*
  • Canine herpesvirus*
  • Canine distemper virus*
  • Feline calicivirus **
  • Feline syncytia-forming virus**
  • Feline immunodeficiency virus**
  • Bovine herpesvirus 4R**

Parasites

  • Capillaria spp
  • Dioctophyma renale

*Not reported in cats.

** Not reported in dogs.

Our observations suggest that bacterial urinary tract infection is a common cause of urinary tract disease in dogs of all ages. In contrast, primary bacterial urinary tract infections are uncommon causes of urinary tract disease in kittens or adult cats younger than 10 years of age (). Over a 5-year period, we did not observe primary bacterial urinary tract infection in a cat younger than 6 months. A staphylococcal urinary tract infection was, however, observed in a 5-month-old domestic short-haired male cat after urethral catheterization for relief of urethral obstruction due to a matrix-crystalline urethral plug. Clinical manifestations of urinary tract infection are similar regardless of causative agent and are often indistinguishable from noninfectious causes. Bacterial urinary tract infections confined to the lower urinary tract (urinary bladder and urethra) are typically associated with clinical signs of dysuria and pollakiuria and with urinalysis findings of pyuria, he-maturia, and proteinuria (). Signs characteristic of upper urinary tract involvement depend on the degree of renal parenchymal involvement and duration of the disease. Other potential sequelae of bacterial urinary tract infection include septicemia, discospondylitis, chronic renal failure, urinary incontinence, and urinary obstruction due to formation of uroliths or matrix-crystalline urethral plugs. Most struvite uroliths in dogs and up to 10% of struvite uroliths in cats develop as a consequence of bacterial urinary tract infection with urease-producing microorganisms ().

Table Factors Affecting Drug Disposition in Immature Dogs and Cats

Absorption

  • Decreased or irregular gastrointestinal motility
  • Increased intestinal permeability (neonates)
  • Increased gastric pH
  • Decreased muscle mass and blood flow

Distribution

  • Larger volume of distribution
  • Increased percentage of total body water
  • Increased percentage of extracellular water
  • Decreased plasma protein concentrations
  • Decreased body fat

Metabolism and Excretion

  • Decreased hepatic metabolism
  • Decreased renal function
  • Lower glomerular filtration rate
  • Reduced renal blood flow
  • Decreased renal tubular function

Establishing a diagnosis of bacterial urinary tract infection depends on routine laboratory evaluation consisting of urinalysis and quantitative urine culture. Although urinalysis findings of hematuria, pyuria, proteinuria, and bacteriuria are consistent with bacterial infection, caution must be used in establishing a diagnosis of bacterial urinary tract infection on the basis of urinalysis alone. The constellation of hematuria, pyuria, and proteinuria are nonspecific findings indicative of urinary tract inflammation that may result from infectious or noninfectious causes of urinary tract disease. Observation of bacteria in urine sediment is suggestive, but not conclusive, evidence for establishing a diagnosis of bacterial UTI. Use of quantitative urine cultures have largely circumvented problems of interpreting urine sediment findings and provide the most definitive means of confirming and characterizing bacterial urinary tract infection ().

Because most puppies and kittens with significant bacteriuria have a secondary UTI, survey and contrast radiography, ultrasonography, exfoliative cytology of urine sediment, and biopsy of urinary tract tissues may be of value for identifying predisposing factors. Antimicrobial agents remain the cornerstone of therapy for a bacterial UTI. Because compromised host defense mechanisms are extremely important factors in the pathogenesis of urinary tract infections in puppies, identification and correction of the abnormalities are necessary prerequisites of successful long-term treatment. Once the causative agent is identified, antimicrobial agents should be selected on the basis of bacterial culture and susceptibility tests, safety, and potential expense. We emphasize that drug absorption, metabolism, and excretion may be substantially different in puppies and kittens compared with adults (Table Factors Affecting Drug Disposition in Immature Dogs and Cats) (). Antimicrobial agents and dosing schedules routinely used in the treatment of urinary tract infections in adults may be associated with serious adverse reactions or apparent therapeutic failures when empirically used for puppies and kittens (Table Antimicrobial Agents Available for Therapy of Urinary Tract Infection in Immature Dogs and Cats). Because of their safety, wide therapeutic index, and ability to achieve high urine concentrations, β-lactam antibiotics (i.e., penicillin, ampicillin, amoxicillin-clavulanic acid, and cephalosporins) are recommended. Urine should be recultured 3 to 5 days after initiation of therapy to confirm sterilization of urine. Antimicrobial therapy should be continued until there is clinical and laboratory evidence of response as determined by clinical signs, urinalysis, and bacterial culture.

Mycoplasma and Ureaplasma organisms have been associated with naturally occurring or experimentally induced urinary tract disease in humans, dogs, sheep, and rats (). In our experience, Mycoplasma urinary tract infections in dogs younger than 6 months have been opportunistic infections that have invariably occurred as a sequela to preexisting lower urinary tract disease. The urinary tract infection is often preceded by indwelling urinary catheterization and administration of β-lactam antimicrobial agents. In two cases, Mycoplasma urinary tract infections were associated with clinical signs of lower urinary tract disease (dysuria, urinary incontinence, and pyuria), which resolved after appropriate antimicrobial therapy. Although Mycoplasma and Ureaplasma organisms have been isolated from the genitourinary tract of cats, their role as causative agents in feline urinary tract disease is uncertain. Diagnosis of Ureaplasma or Mycoplasma urinary tract infections requires isolation of the organisms from suitable urine or tissue samples. Mycoplasma and Ureaplasma organisms are fragile and fastidious with exacting growth requirements, which may vary considerably among Mycoplasma species. Successful recovery and identification of these organisms requires careful collection and transport of specimens and use of appropriate growth media and specific cultivation methods. Because many laboratories are not prepared to culture Mycoplasma and Ureaplasma, it is advisable to consult with laboratory staff for specific recommendations before collection and submission of samples.

Table Antimicrobial Agents Available for Therapy of Urinary Tract Infection in Immature Dogs and Cats

Antimicrobial Metabolism /

Route of Elimination

Toxicity and Adverse Reactions Therapeutic Recommendations
Penicillin G Renal Low toxicity Parenteral routes preferred for

neonates*; consider higher dose and longer intervals for patients <3 mo

Ampicillin / amoxicillin Renal Low toxicity; may alter GI flora Parenteral routes preferred for

neonates*; consider higher dose and longer intervals for patients <3 mo

Amoxicillin-

clavulanic acid

Renal Low toxicity; may alter GI flora Consider higher dose and longer intervals for patient <3 mo
Cephalosporins

Cefadroxil (1st gen)

Cefoxitin (2nd gen)**

Ceftdofur (3rd gen)**

Others**

Renal Low toxicity; interaction with aminoglycosides? Parenteral routes preferred for neonates*; consider higher dose and longer intervals for patients <3 mo
Fluoroquinolones Enrofloxacin Ciprofloxacin** Renal; hepatic Erosion of articular cartilage in dogs and cats <8 mo Avoid prolonged high-dose therapy; consider lower dose and longer intervals for patients <5 mo
Trimethoprim-sulfadiazine Renal; hepatic KCS; hepatitis; anemia; leukopenia; pyrexia, polyarthritis Consider lower dose and longer intervals for patients <5 mo
Aminoglycosides

Gentamicin

Amikacin**

Renal Nephrotoxic; ototoxic; toxicity potentiated by pyrexia, dehydration, sepsis, furosemide, potassium depletion, and possibly by cephalosporins and NSAIDs Avoid if possible; consider higher dose and longer interval; therapeutic drug monitoring recommended
Tetracyclines

Tetracycline

Oxytetracycline

Doxycycline**

Renal; hepatic Anabolic; chelate calcium; inhibit bone and enamel formation; discoloration of teeth; may alter GI flora Avoid for patients <5 mo
Chloramphenicol Hepatic Dose-dependent bone marrow suppression Avoid for patients <5 mo

GI = gastrointestinal; gen = generation; KCS = keratoconjunctivitis sicca; NSAIDs = nonsteroidal antiinflammatory drugs.

*Avoid intramuscular route because of small muscle mass and reduced blood flow in puppies and kittens.

**Not approved for use in dogs or cats in United States.

Urolithiasis

Urolithiasis may result from multiple congenital and/or acquired physiologic and pathologic processes (). Thus, urolithiasis should not be conceived of as a single disease but rather as a sequela of one or more underlying abnormalities. Although urolithiasis tends to be a disease of middle to older aged animals, 1.6% of canine and 1.3% of feline uroliths analyzed at the Minnesota Urolith Center were obtained from animals 11 months of age or younger. Most urolith mineral types observed in adults have been encountered in puppies and kittens (). Struvite, however, was the most common urolith mineral type identified, comprising approximately 65% of total uroliths analyzed. In our experience, most struvite uroliths encountered in immature animals have been induced by bacterial urinary tract infection with urease-producing microorganisms ().

Infection-induced struvite (magnesium ammonium phosphate) uroliths develop as a consequence of bacterial urinary tract infection with urease-producing microorganisms (especially staphylococci) (). Clinical manifestations of urolithiasis vary and depend on (1) urolith number, location, size, shape, and surface characteristics; (2) local and systemic effects of underlying disease processes; and (3) presence of sequelae (UTI and urinary obstruction) (). Most struvite uroliths are located in the urinary bladder and/or urethra and are typically associated with lower urinary tract signs. Uroliths located in the bladder neck or urethra may cause partial or complete urine outflow obstruction and signs of obstructive uropathy. Uroliths are usually suspected on the basis of characteristic findings obtained by history and physical examination. We emphasize, however, that most uroliths are not reliably detected by abdominal palpation. Urinalysis, urine culture, and radiography may be required to differentiate uroliths from other causes of congenital or acquired lower urinary tract disease (Table Problem-Specific Database for Urolithiasis in Immature Dogs). Once urolithiasis has been confirmed, follow-up evaluation is essential to characterize the extent of disease and to identify predisposing abnormalities. Because quantitative stone analysis provides the most definitive diagnostic, prognostic, and therapeutic information, any uroliths removed or recovered from the urinary tract should be quantitatively analyzed to determine their mineral composition ().

Objectives of management of infection-induced struvite urolithiasis include (1) relief of obstruction to urine outflow when necessary, (2) elimination of existing uroliths, (3) eradication or control of UTI, and (4) prevention of recurrence of uroliths (). Surgery has been the traditional approach for management of all types of uroliths, especially in young dogs and cats. The combined use of short-term calculolytic diets (Prescription Diet Canine s/d, Hill’s Pet Products) and antimicrobial agents has, however, successfully induced dissolution of urocystoliths presumed to be infection-induced struvite in immature dogs (). Despite the feasibility of medical dissolution of struvite uroliths in immature dogs and cats, consumption of calculolytic diets is associated with potential hazards. If initiated, calculolytic diets should not be given for more than approximately 4 weeks, and animals should be monitored carefully for evidence of nutritional deficiencies (especially protein malnutrition). Although a calculolytic diet designed to dissolve feline struvite uroliths (Prescription Diet Feline s/d, Hill’s Pet Products) is not protein restricted, its use by immature cats may be associated with development of metabolic acidosis, anorexia, and dehydration (). Eradication and/or control of urinary tract infection caused by urease-producing bacteria is the single most important factor in preventing recurrence of most infection-induced struvite uroliths. Because most bacterial urinary tract infections in immature animals are associated with abnormal host defenses, identification and elimination of predisposing factors are essential for long-term prevention.

Table Problem-Specific Database for Urolithiasis in Immature Dogs

  1. Medical history
  2. Note age, sex, and breed
  3. Note diet and use of supplements or drugs
  4. Note changes in micturition and/or character of urine
  5. Note if uroliths have been voided
  6. Physical examination
  7. Palpate kidneys for number, size, shape, position, consistency, and pain
  8. Palpate urinary bladder for size, shape, consistency, position, and grating or nongrating masses
  9. Palpate urethra per rectum for size, shape, and urethral or periurethral masses

III. Complete urinalysis

IV Quantitative urine culture

V Complete blood count

  1. Serum biochemistries
  2. Urea nitrogen and creatinine concentrations
  3. Total protein and albumin concentrations
  4. Hepatic enzyme activities

VII. Survey abdominal radiographs

VIII. Characterize urinary tract abnormalities

  1. Urinary tract ultrasonography
  2. Consider excretory urography
  3. Consider contrast cystography
  4. Bladder or kidney biopsy during cystotomy or nephrotomy
  5. Postsurgical survey abdominal radiographs
  6. Quantitative stone analysis

 

Selections from the book: “Veterinary pediatrics: dogs and cats from birth to six months”. Johnny D. Hoskins. (2001)