Urogenital disorders of ferrets and rabbits (Proceedings)

Although many diseases of the urinary and genital systems are similar in many aspects in all mammals, there are features and presentations which are unique to certain species. Ferrets and rabbits each have specific disease presentations, and the understanding of these disorders is essential in recognizing normal and abnormal, and treating these pets. Although diagnostic evaluation is similar, etiologies, interpretation of laboratory results, and therapeutic strategies may vary substantially. A thorough understanding will lead to the most rapid, effective treatment plan.

General principles

Anatomy

Similar to that of other mammals. Kidneys are usually radiographically evident in the retroperitoneal space in both species, surrounded by fat. Rabbit kidneys may be radiographically located more ventrally than usual due to the presence of retroperitoneal fat. The bladder is cranial to the pelvic inlet and easily palpable when full.

Evaluation

When azotemia is present, determine whether prerenal, renal, or postrenal. Assess chronicity and duration of renal disease.

Physical examination

Assess hydration, renal discomfort, kidney size and shape, presence of other abdominal masses, and urinary obstruction.

Urinalysis

Essential in evaluation of the urinary system – polyuria, hematuria, casts, proteinuria, crystalluria, or isosthenuria accompanying dehydration all are indicators of urinary disease. Normal urine pH values in carnivores are acidic, and are alkaline in herbivores. Microcytic, hypochromic, nonregenerative anemia, hyperphosphatemia, hypocalcemia, and metabolic acidosis often accompany chronic renal failure.

Radiography

Radiographs are ideal for detection of calculi (bladder, renal, urethral, or ureteral) or calciuria, as well as prostatic or uterine enlargement. Excretory urography (IVP-Intravenous pyelography) is useful to detect obstruction and hydronephrosis, and to evaluate renal perfusion. Contrast cystography can be used as in other species for evaluation of the bladder and urethra. Both sexes of rabbits can be easily catheterized; male ferrets, however, are extremely difficult to catheterize and always require sedation. There is a j-shaped os penis, which is exteriorized by placing pressure on the base of the penis, and the urethral opening is not quite at the distalmost aspect of the penis. Female ferrets are extremely difficult to catheterize.

Ultrasound

An excellent diagnostic tool for evaluating the renal system as well as other organs. Also enables aspirates of masses or fluid-filled structures, and can be used to guide renal biopsies. (Note: due to the small patient size, there can be increased risk of injury to the renal vessels in small patients.)

Nuclear scintigraphy

Can be used to determine glomerular filtration rate (GFR) in mammals, and can assess each kidney individually. This is the most accurate assessment of renal function. Although not yet described for ferrets or rabbits, this is an emerging technique in veterinary medicine which enables assessment of GFR in each kidney individually with no patient risk other than anesthesia. (Note: the author has performed GFR scans in ferrets and in rabbits, although there are no published normal values for comparison.)

Renal or bladder biopsy is performed as in other species.

Species specifics

Ferrets

Anatomy

Males have a J-shaped os penis. There is prostatic glandular tissue in ferrets, and although there is controversy among anatomists whether it is truly a prostate gland, it is a clinically significant structure which, when enlarged, can lead to urethral obstruction. There is a pronounced curve to the urethra as it crosses the pelvic rim.

Diagnostic variations

Ferrets normally have very low serum creatinine (normal 0.4-0.6 mg/dL), and any increase may be clinically significant. Even in severe renal failure, creatinine levels rarely elevate. BUN levels have been reported as high as 404 mg/dL with creatinine levels remaining around 2.0 mg/dl, with histologic confirmation of renal disease. Elevation of BUN in the presence of clinical signs should be considered as potentially renal in origin. Urine specific gravity along with hematocrit, phosphorous, potassium, calcium, and carbon dioxide may aid in the diagnosis of renal disease.

Normals

Maintenance fluid/average fluid consumption: 75-100 ml q24 hours. Urine output: 26-28 ml q24 hr. Bladder volume: 10ml. Urine pH: 5.0 (pure carnivores). Trace proteinuria normal.

Disorders

Renal cysts

Common in ferrets, usually benign incidental findings. Polycystic kidneys, which are much less common, may be associated with renal compromise when cysts replace a large percentage of normal renal architecture. If unilateral, nephrectomy may be beneficial. No cure is available.

Hydroureter/hydronephrosis

Uncommon, most cases due to ligation during surgical procedures or secondary to urinary obstruction. Diagnose based on palpation, confirm with ultrasound or IVP as in other species. Treatment is unilateral nephrectomy unless the obstructing agent can be removed and renal function remains in that kidney.

Urolithiasis/calculi

Most common are macroscopic struvite calculi. Disease due to crystalluria is not common. There appear to be two predisposing factors: 1) increased urine pH, or 2) pregnant or nursing females on a poor quality diet. Because ferrets are pure carnivores, the metabolism of animal proteins keep the urine pH low; feeding of excessive vegetables or poor quality diets can lead to elevation of urine pH. Mineral content is not a factor in the formation of calculi in ferrets. Clinical signs resemble other mammals –stranguria, pollakiuria, hematuria, inappropriate urination, obstruction. Radiography and ultrasound will often provide a diagnosis. In the presence of uroliths, surgery is required. Modify diet appropriately. In rare cases, urinary acidifiers are necessary; use at feline doses.

Cystitis/pyelonephritis

Low incidence. Suspect an underlying disease or neoplasia. Similar to other species. Diagnose by urinalysis and culture and sensitivity. Continue antibiotics for a minimum of 3 weeks for cystitis; 6 weeks if pyelonephritis. Fluid therapy is indicated if pyelonephritis is present.

Prostatic/paraurethral cysts

A syndrome seen in adult male ferrets is obstruction of urinary outflow by prostatic enlargement caused by hyperadrenocorticism. The excessive androgens produced by the adrenal gland act on the prostate, causing proliferation of the glandular tissue and partial or complete obstruction. The prostate may develop into a large cystic or cavitary mass, or may become abscessed. This structure often has direct communication with the bladder or urethra, which may be remarkably wide and may allow for free flow of urine between the bladder and prostate. Signs include stranguria, dribbling and preputial wetness, and partial or complete obstruction. Other signs of hyperadrenocorticism may be absent. The bladder is readily palpable in most cases, and often the prostate is also palpable. Hospitalize these patients immediately and treat as any other obstructed mammal: Intravenous fluids, and immediate relief of the obstruction. Catheterization of males can sometimes be performed with a tomcat catheter or a 3.5 french red rubber catheter; in many males the urethra may be too narrow to permit passage of a 3.5 fr. A 3.0-fr catheter is made by Cook veterinary products (Slippery Sam), and is an appropriate length and diameter. Retract the prepuce until the os penis is clearly visible (it may look like the bone is protruding; it is actually covered by mucosa). The opening is on the ventral aspect of the os penis, and can sometimes be located by use of a small piece of nylon suture, which can also be used to guide the catheter into the opening. Use a closed collection system until the prostate begins to shrink. If catheterization is not possible, perform cystocentesis with a 25-ga butterfly needle to relieve the obstruction. Tube cystostomy may be necessary in severe cases. Treatment is removal of the affected adrenal gland. Hormone therapy may be attempted (lupron), and this may help decrease hormone levels and begin decreasing the size of the prostate within 72 hours. This can be used to stabilize the patient during dieresis, to make them a better surgical candidate. (The author feels that surgery is preferable to hormone therapy for long term management in males with obstruction.) If the prostate is abscessed, then omentalization is recommended. If it is cystic, it can either be drained or left alone and will begin to shrink rapidly. Androgen levels will decrease within days after surgery. (NOTE: Females with adrenal disease will develop vulvar enlargement in many cases but do not develop obstruction.

Neoplasia

Rare as a primary neoplasia of the urinary system. Lymphoma may lead to increase of sublumbar lymph nodes and subsequent signs of urinary obstruction. The author has had success with radiation of these nodes to provide rapid shrinkage and relief of obstruction.

Persistent estrus

Intact females are induced ovulators, and in the absence of breeding may develop hyperestrogenism. Clinical signs in the early stages are limited to swollen vulva and alopecia, but thrombocytopenia and bone marrow suppression will occur if untreated. Treatment is ovariohysterectomy, but is often not possible if thrombocytopenia and bone marrow suppression are already present. Multiple transfusions may be required. Swollen vulva is also associated with adrenal disease (see above).

Rabbits

Anatomy

Kidneys are unipapillate. Penis is caudal to testes. No os penis. Females have no uterine body; two horns open into two separate vaginas. Two cervices.

Diagnostic variation

Rabbits possess the ability for almost complete intestinal absorption of all dietary calcium. Excess absorbed calcium is then excreted in the urine. The percent of calcium excreted through the urine in rabbits is 45-60%, as compared to 2% in most mammals. Because of this unique feature, blood calcium levels in rabbits may be much higher than other mammalian species without any associated clinical signs. Calcium levels up to 15-16 mg/dl may be present in rabbit blood without apparent clinical manifestations. Calcium carbonate or calcium oxalate crystals in the urine are normal. Urine is cloudy.

Normals

Maintenance fluid/average fluid consumption: 100 ml q24 hours.

Urine output: 130 ml/kg q24 hr. (additional fluid may be taken in through large quantities of fresh leafy vegetables.) Urine pH: 8.2. Porphyrin pigments are occasionally produced and may give an orange-brown color to urine. Urine is cloudy due to the excretion of calcium. Trace protein is normal.

Disorders

Calciuria

The accumulation of a calcium "sand" or "sludge" in the urine of rabbits is extremely common. This syndrome in rabbits is directly related to the consumption of excessive dietary calcium. (NOTE: radiographic evidence of calcium in the bladder in small amounts is normal.) Rabbits with calciuria may demonstrate any or all of the following clinical signs: urinary incontinence, dribbling or inappropriate urination, stranguria, bouts of vague, nonspecific discomfort, lethargy, inappetence/anorexia, and persistent urine scald. In some rabbits, the calcium sand will form a precipitate; the rabbit will eliminate the clear "supernatant", allowing the sediment to remain in the bladder. This can lead to chronic irritation of the bladder, urine retention, bladder infection, and in severe cases, distention of the bladder leading to bladder atony and overflow incontinence. Treat with fluid therapy, bladder lavage as needed, antimicrobials if indicated, diet modification. (See below).

Cystic Calculi

Bladder stones are another manifestation of this problem. The clinical presentation is similar to other mammals, often with nonspecific signs including anorexia, weight loss, hematuria, stranguria, grinding teeth, hunched posture, and urinary obstruction. Stones may also develop in the kidneys or ureters, leading to significant renal compromise and sometimes permanent damage. Treatment for calculi is surgery whenever possible. Note: do not assume that a renolith in one kidney is causing enough loss of function to warrant nephrectomy. Prior to nephrectomy, perform an IVP to ascertain the perfusion of the remaining kidney.

These conditions will reoccur in nearly 100% of cases unless predisposing factors in the diet and environment are corrected. Predisposing factors include obesity, lack of exercise, and excessive dietary calcium. Rabbits with calciuria or calculi must be placed on very restricted pellets (maximum ⅛ cup per 4 lb. body weight). Complete elimination of pellets may be necessary in severe cases. Alfalfa hay should be replaced with lower calcium hays such as timothy or other grass hays. Leafy vegetables should be offered in abundance to increase dietary fiber content. It is usually not necessary to restrict consumption of calcium-rich vegetables once the rest of the diet is corrected, but may be important in severe cases. Follow up radiographs and bloodwork are recommended to monitor progress and prevent further problems.

Encephalitozoon

Encephalitozoon cuniculi is a microsporidian protozoal organism, transmitted by the urine-oral route. Spores migrate to kidney and brain. Clinical signs may not be apparent, but the kidneys may have small stellate foci throughout which are generally seen at necropsy. Most rabbits will remain asymptomatic through life, but some immunocompromised rabbits may develop signs associated with lesions in the brain. The parasite is shed in the urine for up to 3 months after infection, and recent work indicates that it may be shed sporadically throughout the life of the infected animal.

Neoplasia

Renal neoplasia is uncommon, but lymphoma, carcinoma, and embryonal nephromas may develop. Neoplasia of the female reproductive tract commonly occurs. Uterine adenocarcinoma is the most common neoplasia of female rabbits, with an incidence as high as 80% in some breeds. Metastasis is common but slow, often > 1-2 years after the detection of the uterine neoplasia. Masses may involve one or both uterine horns. Clinical signs include hematuria or vaginal bleeding, and a palpable uterus. Presumptive diagnosis is made ultrasonographically and confirmed histologically. Radiographs are also useful, although visualization of the uterus is normal in rabbits. Treatment is ovariohysterectomy; prognosis is good as long at there are no metastases. Monitor at 3-6 month intervals for metastasis. Uterine endometrial hyperplasia may be a part of a continuum in the development of uterine adenocarcinoma.

Pyometra

Uncommon. Clinical signs resemble mammals – lethargy, anorexia, possibly vaginal discharge. Most common organisms are Pasteurella multocida and Staphylococcus aureus. Treatment is ovariohysterectomy, along with appropriate antimicrobial therapy and supportive care as indicated.

Treponema

(Rabbit syphilis) Spirochete. Transmitted by direct contact. More prevalent in breeding colonies of rabbits, and may be subclinical until a stress occurs. Clinical lesions are dry, flaky crusts in the regions of the genitalia, nares, commisures and filtrum of the mouth, which can spread to the face, chin, and eyelids. Early lesions may be red vesicles. Diagnosis can be confirmed with darkfield microscopy or biopsy. Treatment is with injectable penicillin (Pen G Procaine and banzathine, 42,000-84,000 IU/KG SQ q7 days for 3 treatments).

Pregnancy toxemia

Occurs in the last 7-10 days of gestation. Obese rabbits are predisposed. Clinical signs include lethargy, extreme weakness, depression, ataxia, coma, or acute death. Diagnosis can be confirmed biochemically, with hyperphosphatemia, hypocalcemia, ketonemia, ketonuria, proteinuria, and hyperkalemia. Treatment is supportive, but care must be aggressive. Prognosis is poor.

References

Paul-Murphy J. Reproductive and urogenital disorders. In: Hillyer, EV and Quesenberry, KE, eds.: Ferrets, Rabbits, and Rodents. Philadelphia, PA: WB Saunders, 1997;202-211.

Harkness JE, Wagner JE. The Biology of Medicine of Rabbits and Rodents. (fourth ed.) Media, PA: Lea and Febiger, 1995.

Antinoff, N. Urinary disorders of ferrets. In: Fudge AM, Phalen, DN. (eds). Seminars in Avian and Exotic Pet Medicine, 7(2), 1998;89-92.

Rosenthal KL, Peterson ME. Stranguria in a castrated male ferret. J Am Vet Med Assoc 209:62-64, 1996.

Marini RP, Esteves MI, Fox JG. A technique for catheterization of the urinary bladder in the ferret. Lan Amin 28:11, 1994.