If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Diseases involving the urinary tract are arguably less common in ferrets than in some other domestic animals, but such diseases are often complex and can be particularly challenging to treat. Urinary tract disease in pet ferrets is often related to abnormalities in other body systems, including secondary reproductive organs (eg, the prostate gland) and the adrenal glands. Although the incidence of primary reproductive tract disease has declined dramatically since commercial breeding farms began to neuter ferrets at 5–6 weeks of age, adrenal disease and associated disease syndromes affecting both the urinary and reproductive tracts are diagnosed with notable frequency [
This article begins with a description of the anatomy and physiology of the ferret's urinary and reproductive tracts. Although various anatomic and physiologic features are similar to those of the dog and cat, there are some important differences in the ferret that impact diagnostic interpretation and treatment. Disease syndromes presented focus on those that are clinically relevant to the veterinarian working with pet ferrets. Although most domestic ferrets in the United States are neutered by the time of sale, a minority of private individuals breed ferrets and sell intact kits. In addition to common urinary tract syndromes, reproductive syndromes that may be infrequently encountered, or at least included in the differential diagnosis involving more common diseases, will be discussed. For a more complete discussion of reproductive tract disease involving the intact jill or hob as well as breeding and reproduction, the reader is referred to other sources [
Clinical anatomy of the urinary and reproductive tracts
The kidneys of the ferret lie in the sublumbar retroperitoneal space and have an average size of 2.40–3.0 cm in length, 1.2–1.35 cm in width, and 1.1–1.35 cm in thickness [
]. The cranial pole of the right kidney is situated at the level of T14, and the cranial pole of the left kidney lies approximately 0.2 cm caudal to L1. The ferret kidney contains a renal pelvis. Each ureter runs along the ventral aspect of the psoas muscle and empties into the dorsolateral surface of the bladder immediately caudal to the bladder neck. The urinary bladder measures approximately 1 cm in diameter and 2 cm in length when empty, and it can accommodate approximately 10 mL of urine at low pressure (5 cm H2O) [
]. Interestingly, stimulation of either the hypogastric (sympathetic) or sacral (parasympathetic) nerve causes bladder contraction in the ferret, whereas in other animals (eg, the cat), increased sympathetic tone usually causes detrussor muscle relaxation [
]. The bladder wall in the ferret is extremely thin, and sedation may be necessary for cystocentesis in very active ferrets in order to prevent bladder wall laceration. The urethra originates from the urinary bladder near the cranial aspect of the pelvic inlet.
In the intact female ferret, paired ovaries are located caudal to the kidneys where each is attached to the body wall by a suspensory ligament at approximately the level of the last rib. The uterine horns fuse to form a short body at the caudal aspect of which is a single cervix. The urethral orifice lies approximately 1.0–1.5 cm cranial to the clitoral fossa on the ventral floor of the vaginal vestibule [
In the intact male ferret, the testicles are located ventral to the anus as in the cat. Normally, each testis and its spermatic cord (composed of the deferent duct, deferent artery and vein, and testicular artery and vein) are covered by the vaginal sac, a peritoneal pouch, which extends through the inguinal canal prior to the testicular descent [
]. As each testicle descends, the spermatic cord is carried through the inguinal ring, which is a small potential opening in the ferret. The penis is located on the caudoventral abdomen as in the dog, and the os penis lies dorsal to the penile urethra. The prostate gland, the only reproductive gland in the male ferret, surrounds the proximal urethra at the base of the bladder. Normal prostatic tissue is relatively indistinct in young male or castrated ferrets, appearing only as a small (11 mm long×6 mm wide) fusiform mass around the proximal part of the urethra. Perhaps this is the reason for previous reports in the literature stating that male ferrets had no detectable prostate glands at necropsy [
]. Secretions from the prostate gland enter the urethra via multiple small tubules or ducts as opposed to the long prostatic ducts found in many other species [
]. The prostatic parenchyma normally contains compound tubuloalveolar glands separated by fibrous connective tissue, and the glandular tubules are normally lined by cuboidal (if distended with secretory material) or columnar (if empty) cells. The urethra makes an acute turn ventrally as it exits the pelvic canal, then it travels the length of the penis in which it lies ventral to the os. The distal aspect of the os penis is J-shaped, curves dorsally, and is covered by a thin layer of tissue. The urethral orifice is a slit-like opening on the ventral surface of the glans approximately 2–4 mm proximal to its tip.
Clinical physiology of the urinary and reproductive tracts
Ferrets differ from other domestic mammals and humans in that elevations in the concentration of blood urea nitrogen (BUN) in cases of renal failure are not always accompanied by increases in the concentration of serum creatinine above the normal range [
]. This can be confusing to the veterinarian who is accustomed to evaluating both BUN and creatinine levels in dogs and cats. Even in cases of severe renal disease, elevated levels of creatinine are uncommon in the ferret, whereas BUN levels can be extremely high. In one report of a clinical population of ferrets evaluated over 15 years, BUN measurements were sometimes as high as 500 mg/dL, but creatinine levels rarely exceeded 3.0 mg/dL [
]. The discrepancy between BUN and serum creatinine levels remains unexplained, but various hypotheses have been offered. The mean creatinine level in ferrets is lower (0.4–0.6 mg/dL) and the range is narrower (0.2–0.9 mg/dL) than in dogs and cats [
]. This may mean that any elevation in creatinine is significant in a ferret. In addition, mechanisms of creatinine excretion other than free glomerular filtraton, for example, renal tubular secretion or enteric degradation, may be relatively more important in the ferret compared to other species [
Clinically, glomerular function is evaluated in most animals by measurement of BUN and serum creatinine concentrations, because both are freely filtered across the glomerular basement membrane. However, creatinine measurement is not particularly sensitive in the ferret, and BUN may be influenced by nonrenal factors (eg, gastrointestinal bleeding). In addition, an increase in the serum concentration of both BUN and creatinine in most mammalian species does not occur until approximately 75% of renal function is lost [
]. Therefore, glomerular filtration rate (GFR) can often be more precisely measured by calculating the plasma clearance of an infused substance, for example, inulin. In one study, inulin clearance was found to be an adequate measure of GFR in ferrets as it is in other species [
Daily fluid requirements for ferrets have not been established. Water consumption has been reported to average 75–100 mL/kg per day, and that is the dose range generally used to maintain hydration in ferrets [
]. Reports of urine output vary widely. In a study of 40 male and 20 female ferrets fed dog food (ages not reported), urine output ranges of 8–140 mL/24 h were reported for females and 8–48 mL/24 h for males [
]. Normal urine specific gravity has not been reported for ferrets, and in this author's experience, it can vary widely in clinically normal ferrets. Bladder urine osmolarity can be as high as 2000 mOsm/L, indicating a significant concentrating ability and suggesting that the ferret may have descended from a desert-dwelling animal [
]. Urine pH is dependent to a large degree on diet. The normal urine pH for domestic ferrets is reported to be 6.5–7.5, but high-quality, meat-based diets should produce a urine pH closer to 6.0 [
]. Small amounts of urine bilirubin, detected by urine dipsticks and unaccompanied by hyperbilirubinemia, are not uncommon in ferrets. The cause of bilirubinuria in clinically normal ferrets is unknown.
Female ferrets are usually sexually mature by 7–10 months of age and males by 8–12 months [
]. Estrogen levels are elevated during estrus, and clinical signs usually include vulvar swelling and serous vulvar discharge. Cytology from vaginal lavage reveals 90% keratinized superficial cells during estrus, and neutrophils are common during all stages of the ferret's estrous cycle [
Most of the techniques used during the diagnostic workup of the ferret patient with suspected urinary or reproductive tract disease are similar to those used with dogs and cats. Venipuncture to collect volumes of blood >0.5 mL is best accomplished via the jugular vein or one of the large veins accessed at the sternal notch [
]. Survey radiography, ultrasonography, and other imaging modalities are used as with dogs and cats. Specific techniques for urethral catheterization of the ferret patient as well as a discussion of contrast urography are included below.
Urethral catheterization
Urethral catheterization in the ferret requires anesthesia, even with depressed patients. Intravenous administration of diazepam or addition of a few drops of dilute lidocaine to the urethral flush may help relax the urethra [
]. Catheterization of the male ferret is especially challenging due to the small diameter of the penile urethra and the acute angle of the urethra at the caudal aspect of the pelvic canal. This is made more difficult in cases of extraluminal compression of the proximal urethra (eg, due to prostatomegaly). With the ferret in dorsal recumbency and using sterile technique, the penis is exteriorized from the prepuce. If the prepuce or the tip of the penis is swollen, a small incision can be made in the preputial opening to allow exposure. Identification of the urethral orifice is facilitated with magnification and a 24-gauge peripheral catheter, which is slid tangentially down the penile tip until it passes into the urethral opening on the ventral surface of the glans. Passage of a blunt-tipped needle (eg, a sterile, filed hypodermic needle with the bevel removed) and retrograde flushing has been described to aid dilation of the urethra for passage of a catheter [
]. Tomcat catheters are not long enough to seat well in the bladder of most ferrets. Alternative choices include a 20- to 22-gauge, 8-inch jugular catheter (Fig. 1); a 3.5-Fr red rubber tube; or a 3.5-Fr, 14-cm urinary catheter specifically developed for use in ferrets (Slippery Sam, Cook Veterinary Products, Spencer, IN). Water-soluble lubricant facilitates catheterization, and an intravenous catheter guide wire or a sterile guitar string can be used as a catheter stylet to negotiate the acute turn of the urethra at the ischial arch [
]. Caution must be exercised not to perforate the urethra at this point.
Fig. 1Penile urethral catheterization using a 22-gauge, 8-inch jugular catheter. (From Orcutt C. Treatment of urogenital disease in ferrets. Exotic DVM 2001;13(3):31–7.)
Catheterization of the female ferret is easiest with the ferret in ventral recumbency and the hindquarters elevated. Ideally, an otoscope or an endoscope is used to visualize the clitoris on the ventral floor of the vaginal vestibule and the urethral orifice lying approximately 1 cm craniad [
]. If the orifice cannot be visualized, the urinary catheter can be aimed at an acute ventral angle and gently slid along the ventral floor of the vestibule until the orifice is entered.
An indwelling catheter is sutured to the skin using tape butterflies in at least two sites to prevent twisting or traction at its point of exit from the vulva or penis. A soft padded bandage is applied to help prevent contamination. The catheter is attached to a urinary collection system, and tubing is monitored frequently for tangling. An Elizabethan collar, cut down in size from a small cat collar, can be placed to prevent the animal from traumatizing the catheter or attached tubing, but it may be difficult to keep in place in a ferret.
Intravenous pyelogram
Intravenous pyelogram (IVP), or excretory urography, is used to evaluate the size, shape, position, and internal structure of the kidneys, ureters, and urinary bladder; visualize urinary tract calculi (especially those involving the upper urinary tract [kidneys and ureters]); assess the upper urinary tract for masses or obstructive lesions; and localize sites of traumatic disruption in the ureter or bladder [
]. Contrast cystography and/or urethrography provide(s) more detail of the lower urinary tract (bladder and urethra). IVP has been mentioned as a means of evaluating renal function in ferrets with renal pathology [
]. However, in other species, IVP has been shown to be an inaccurate assessment of renal function, in that adequate radiopacification of the renal pelvis and urinary collecting system can occur in animals with grossly elevated BUN and creatinine levels [
]. A more accurate assessment of renal function would perhaps be provided by an inulin clearance test.
In preparation for an IVP, iodinated contrast material is injected into a catheter placed in the ferret's cephalic or saphenous vein. Nonionic iodinated contrast agents are preferable over ionic solutions, because they have fewer potential adverse side effects. In addition, nonionic agents do not provoke osmotic diuresis and subsequent dilution, so radiopacification is improved over that achieved with ionic agents. The relatively higher cost of the nonionic agent is offset by the small size of the ferret. For ferrets, the author typically uses iohexol (240 mg iodine/mL) at a dose of 720 mg iodine/kg.
Disease syndromes
Renal failure
Primary renal failure is not common in ferrets. One clinician with an estimated case load of 1500 ferrets per year reported a total of 28 confirmed cases of true renal failure over a 15-year period [
]. Clinical signs of renal failure in ferrets are often acute (ie, less than a few days' duration) relative to other animals and most often include depression, lethargy, anorexia, weight loss, melena, dehydration, and weakness. Oral ulceration, vomiting, polyuria, and polydipsia are less common in this author's experience. Depending on the disease process involved, abnormal physical examination findings can include dehydration, pallor, cachexia, signs of gastrointestinal (GI) discomfort (bruxism, squinting, ptyalism), abnormal kidney size or shape, discomfort on palpation of the kidneys, abdominal masses, melena, lymphadenopathy, or bladder enlargement.
Initial diagnostics include a complete blood count (CBC), serum biochemical analysis, and urinalysis. Blood gas analysis should be performed on depressed ferrets. The clinician should suspect renal disease in any ferret with an elevated BUN, regardless of the creatinine level. The clinician should determine whether the source of azotemia is prerenal, renal, or postrenal. Clinicopathologic parameters accompanying chronic renal failure can include microcytic, hypochromic, nonregenerative anemia; hyperphosphatemia; hypocalcemia; and metabolic acidosis [
]. Urine abnormalities can include isosthenuria, casts, an elevated number of white or red blood cells, bacteria, crystals, excess protein, or neoplastic cells. Urine bacterial culture and antimicrobial sensitivity testing is indicated in cases with an inflammatory urine sediment. Imaging modalities (radiography, IVP, or ultrasonography) are necessary to evaluate abnormalities in the kidneys, ureters, bladder, urethra, and adjacent soft tissues as well as the adrenal glands. In dogs and cats, IVP is a safe procedure in the presence of azotemia if the animal has been adequately hydrated [
]. Ultrasound-guided fine-needle aspiration of the kidney can be attempted in anesthetized ferrets that have no evidence of coagulation abnormalities.
Depending on etiology, treatment guidelines are similar to those used for dogs and cats. Intravenous fluids can be most accurately delivered by an infusion pump or a calibrated infusate chamber reservoir (Buretrol, Baxter Healthcare, Deerfield, IL). Geriatric animals or those with overt cardiac disease must be monitored carefully for signs of fluid overload. Tissue distribution and route of excretion must be considered when selecting antibiotics and other therapeutics in cases of renal disease. Ferrets with signs of GI discomfort should be treated prophylactically for Helicobacter-induced gastritis (amoxicillin, 20 mg/kg orally every 12 hours; metronidazole, 20 mg/kg orally every 12 hours; famotidine, 0.5 mg/kg orally, intravenously every 24 hours), and sucralfate (125 mg per ferret orally every 6–8 hours) should be administered to those with melena [
]. Severe pathology can progress to renal failure, but varying degrees of chronic interstitial nephritis are also commonly seen at necropsy of geriatric ferrets that have died from other causes.
Cystic kidneys
In this author's clinical practice, solitary renal cysts are frequently seen as incidental findings during ultrasound examination or necropsy. Ten to 15% of ferrets necropsied at one institution had renal cysts [
]. Cysts are usually present singly or in small numbers but in some cases can involve a large area of the renal parenchyma. However, even relatively large renal cysts may be clinically insignificant (Fig. 2). Multiple cortical cysts are also often clinically insignificant, but diffuse polycystic disease involving the kidney cortex and/or medulla can result in renal failure [
]. True polycystic disease, reported in other animal species and in humans, usually involves cystic structures in other organs as well as the kidneys. The authors of one report of diffuse cystic disease involving both kidneys in a 3-year-old ferret suggested this case was similar to adult polycystic disease of humans despite the lack of cystic structures found in other organs [
]. There is no treatment for polycystic disease involving both kidneys.
Fig. 2Large renal cyst in an 8.5-year-old female spayed ferret. The ferret's serum biochemical crosshairs indicate the kidney boundries analysis revealed no abnormalities in BUN, creatinine, or phosphorus levels.
Hydronephrosis and hydroureter are relatively uncommon in ferrets, and most of the cases reported have resulted from inadvertent ligation of the ureters during ovariohysterectomy [
]. A hydronephrotic kidney measuring 7×10 cm associated with a carcinoma of undetermined origin, which involved the renal cortical surface, was reported in a 13-month-old female spayed ferret [
]. The authors of the report suspected either a congenital atretic ureter or stricture from neoplasia as a cause of the hydronephrosis; however, histopathologic findings confirmed neither. This author has seen hydroureter and hydronephrosis in ferrets secondary to urethral obstruction by ureteral calculi, paraurethral cysts, and prostatomegaly (Fig. 3).
Fig. 3(A) Sonogram of a 1.5-year-old female spayed ferret with bilateral hydroureter and hydronephrosis secondary to ureteral calculi. This ferret also had cystic calculi and bilateral adrenomegaly. (B) Sonogram illustrating hydronephrosis in the same ferret. Crosshairs indicate the kidney boundaries.
Fig. 3(A) Sonogram of a 1.5-year-old female spayed ferret with bilateral hydroureter and hydronephrosis secondary to ureteral calculi. This ferret also had cystic calculi and bilateral adrenomegaly. (B) Sonogram illustrating hydronephrosis in the same ferret. Crosshairs indicate the kidney boundaries.
Diagnosis of hydronephrosis is made by ultrasonography. A blood sample should be submitted for a CBC and serum biochemical analysis. Pressure atrophy or ischemia of the abnormal renal parenchyma can result in pyelonephritis, so a urinalysis and urine bacterial culture and antimicrobial sensitivity testing should be performed [
]. If only one kidney is involved, a nephrectomy can be performed.
Pyelonephritis
Pyelonephritis is uncommon in pet ferrets and is usually associated with either a urinary infection ascending from the bladder or septicemia. Hemolytic Escherichia coli was reported to be frequently isolated from kidneys of ferrets affected with pyelonephritis at one institution, and other bacteria incriminated are often the same as those involved with cystitis [
]. Clinical signs of pyelonephritis include pyrexia, lethargy, anorexia, and pain on palpation of the kidneys. Blood should be submitted for a CBC and serum biochemical analysis, and urine collected by cystocentesis should be submitted for analysis and bacterial culture and antimicrobial sensitivity testing. The CBC may reveal a leukocytosis, and urinalysis may reveal renal tubular casts, increased numbers of leukocytes and/or erythrocytes, and bacteria. Pyelonephritis can be difficult to distinguish from cystitis, but ferrets are usually not as debilitated by the latter. Treatment for pyelonephritis includes fluid diuresis, parenteral antibacterial treatment (based on sensitivity results), analgesics, and nutritional support.
Glomerulonephropathy
Glomerulonephritis can be caused by Aleutian disease, which is extremely rare in this author's clinical practice. The proliferative glomerulonephropathy caused by Aleutian disease virus is a result of immune complex formation. A report from 1994 on methods for evaluation of GFR in ferrets stated that glomerulonephropathy was the most common lesion observed at necropsy of the ferrets in the study [
]. In that report, older ferrets were more likely to have severe glomerular lesions and to be seropositive for Aleutian disease virus than younger ferrets. Clinical signs of Aleutian disease include chronic wasting, melena, and neurologic abnormalities. Pathogenesis, epizootiology, and diagnosis of the disease is described elsewhere [
Nephrotoxic agents reported to affect ferrets are the same as those that affect other small mammals, however, fatal toxicity can occur with ingestion of much smaller quantities due to the size of the ferret. Ferrets appear to be especially susceptible to zinc toxicosis, and exposure to galvanized metal should be avoided [
]. Clinical signs reported with zinc toxicosis include anemia, melena, icterus, and diarrhea. In a report of ferrets that ingested galvanized powder from caging, 20 animals died of renal failure due to zinc toxicity [
]. The most significant lesions on histopathology were diffuse, subacute nephrosis; gastric mucosal ulceration; and hepatic pericinar fatty infiltration. Zinc levels were highest in the kidneys (785–943 ppm, compared to levels of 110–120 ppm found in the renal tissue of normal ferrets) [
]. Treatment for zinc toxicity includes removal of zinc-containing materials by induced emesis, gastric lavage, or surgical extraction; fluid diuresis; administration of GI protectants (eg, amoxicillin, metronidazole, famotidine, and sucralfate); iron administration; and nutritional support. The efficacy of heavy metal chelation is equivocal in the treatment of zinc toxicosis [
]. In ferrets with severe anemia, a blood transfusion or infusion of a hemoglobin-carrying oxygen compound (Oxyglobin®, Biopure Corp., Cambridge, MA) may be necessary.
Ibuprofen toxicity
Ferrets can pry the tops off child-resistant bottles and chew through plastic containers to reach tablets, pediatric liquid suspensions, and topical ointments containing ibuprofen. Ibuprofen toxicity is thought to be more severe in ferrets than in dogs at similar dosages [
]. The reason for this is unknown. In a retrospective study of ibuprofen ingestion reported in 43 ferrets, the lowest dose resulting in death was 220 mg/kg [
Target organs of ibuprofen toxicity are the central nervous system, GI tract, and kidneys. Clinical effects are the result of the inhibition of prostaglandins' protective effects on the body. Repair of gastrointestinal epithelial cells is inhibited as is secretion of the protective mucous layer in the stomach and small intestine; vasoconstriction is induced in the gastric mucosa; and renal blood flow, glomerular filtration, and tubular ion transport are inhibited [
]. Clinical signs of ibuprofen toxicity include depression, coma, ataxia, tremors, weakness, anorexia, vomiting, gagging, diarrhea, melena, polydipsia, polyuria, and dysuria. Clinical signs were apparent within 8 hours of ingestion in 65% of the ferrets reported in the retrospective study mentioned above, and signs involving the urinary system (eg, polydipsia, polyuria, dysuria, and renal failure) were apparent in 13.7% of the cases [
Diagnosis is presumptive based on the animal's recent history and access to ibuprofen. Initial stabilization includes oxygen therapy to treat brain hypoxia, fluid support, diazepam (1–1.5 mg/kg intravenously or intramuscularly) to control seizures, and thermal regulation [
]. Emesis can be induced in an asymptomatic ferret (3% hydrogen peroxide solution, 2.2 mL/kg) but is effective only within 1–2 hours of ibuprofen ingestion due to the ferret's short GI transit time [
]. If emesis is contraindicated, gastric lavage can be performed in the anesthetized ferret with a cuffed endotracheal tube in place. Activated charcoal adsorbs ibuprofen and can be given at a dose of 1–2 g/kg [
]. Due to the enterohepatic recirculation of ibuprofen, dosing should be repeated. An osmotic cathartic (eg, sorbitol, 3 mL/kg) should also be used in ferrets that are not dehydrated and do not have diarrhea [
]. Blood gas analysis, a CBC, serum biochemical analysis, and urinalysis should be performed on collapsed ferrets, and metabolic derangements should be corrected. Corticosteroid therapy may increase the risk of GI ulceration and should be avoided [
]. Gastrointestinal protectants recommended include misoprostol (1–5 μg/kg orally every 8 hours) or a combination of a sucralfate slurry (125 mg orally every 6 hours) and famotidine (0.25–0.5 mg/kg orally or intravenously every 24 hours) [
]. Nutritional support is critical in avoiding the development of hepatic lipidosis.
Iatrogenic
Drugs with nephrotoxic potential in other small mammals can affect ferrets as well; these include aminoglycosides and nonsteroidal antiinflammatory drugs (see above for ibuprofen). However, overdosages of other medications can result in nephropathy and renal failure. Presumptive acute renal failure was reported in a 3-month-old male castrated ferret, weighing approximately 1.2 kg, that was treated at a pet store for an apparent anaphylactoid reaction to a canine distemper vaccination [
]. Treatment included epinephrine (1 mL intramuscularly; concentration unknown), dexamethasone (1 mL intramuscularly; concentration unknown), and diphenhydramine (20 mg intramuscularly). Commercially available concentrations of epinephrine include 1:1000 (1 mg/mL) and 1:10,000 (0.1 mg/mL); therefore, the epinephrine dose given was 5–50 times the recommended dose (0.02 mg/kg) [
]. Diphenhydramine was administered at approximately 10 times the recommended dose (0.5–2 mg/kg). The ferret experienced progressive azotemia posttreatment, despite fluid diuresis, and cardiac abnormalities were apparent on radiographs and echocardiogram. Necropsy abnormalities included severe multifocal renal tubular necrosis, multifocal acute myocardial necrosis with contraction bands, and multifocal pulmonary edema. The high dose of epinephrine stimulated α-receptors and likely caused massive vasoconstriction, which led to decreased renal blood flow [
]. The resulting anoxia predisposed to acute renal tubular necrosis. Epinephrine also stimulates β1-receptors of the myocardium and causes significantly increased oxygen consumption, which in this case may have caused direct damage to myocytes [
]. Diphenhydramine potentiates the effects of epinephrine. Clinicians accustomed to working with dogs and cats must be aware of the smaller size of ferrets when dosing medications and should always dose on a per kilogram basis.
Cystitis
The incidence of primary cystitis is low in ferrets relative to dogs and cats, and the majority of cases are secondary to other diseases such as prostatic abscessation. In some of these cases, gross pyuria may result in urethral obstruction.
Bacterial organisms cultured most commonly in this author's practice include E. coli and Staphylococcus spp, but other gram-negative enteric organisms have been isolated as well. In some cases, concurrent urolithiasis may be involved. Diagnosis of cystitis is based on urinalysis and urine culture results.
A CBC and serum biochemical analysis should be evaluated for signs of pyelonephritis. Once a urine sample has been submitted for bacterial culture and antimicrobial sensitivity testing, broad-spectrum antibiotic treatment should be initiated pending test results. The preferred antibiotic is one that maintains effective concentrations in the urinary tract, and drugs suitable for use in dogs or cats can be used in ferrets on a per kilogram basis. Choices for empirical treatment pending culture results include amoxicillin/clavulinic acid (12.5 mg/kg orally every 12 hours), trimethoprim sulfa (30 mg/kg orally every 12 hours), or enrofloxacin (10 mg/kg orally every 12 hours) [
]. Antibiotic therapy should be continued for at least 3 weeks then discontinued for 5–7 days prior to repeating the urine culture.
Urolithiasis/urethral obstruction
Urolithiasis is less common in ferrets now than it was in the past due to improved commercial diets and client education regarding the appropriate diet for pet ferrets. Uroliths can occur in ferrets as young as several months old [
]. Other types of uroliths have been anecdotally reported—for example, cystine, calcium oxalate, calcium hydrogen phosphate dihydrate (brushite). Etiologies are unknown, and as in other animals, urinary tract infections may or may not accompany urolithiasis.
Although the complete pathogenesis of struvite urolithiasis in ferrets is unknown, diet is likely to play an important role. Ferrets fed dog food or low-quality cat food containing plant protein have a much higher incidence of struvite urolithiasis than those fed a high-quality feline diet containing animal protein [
]. Struvite crystallization is enhanced in a relatively more alkaline environment (ie, urine pH > 6.5) produced by metabolism of organic acids in plant protein. Ferrets are obligate carnivores, and thus their normal urine pH should be acidic (pH = 6.0) due to the metabolism of cystine and methionine in animal protein [
]. Continuous mobilization of minerals during pregnancy reportedly increases the jill's risk of urolithiasis, but the protein content of the diet is thought to have more impact than the mineral content on the formation of struvite uroliths [
]. However, some ferrets eating an apparently suitable diet can developed struvite uroliths. In a minority of cases, urinary tract infection with urease-producing bacteria (eg, Staphylococcus, Pseudomonas, and Proteus spp.) may predispose the ferret to urolithiasis by inducing alkalinity or causing renal damage, which in turn affects mineral reabsorption [
Clinical signs of urolithiasis in ferrets vary but are similar to those seen in other animals: stranguria, urinary incontinence, hematuria, vocalizing when urinating, frequent attempts at urination, wet fur on the ventrum or perineum, urine dribbling, and excessive licking of the prepuce or perineum. As in other animals, urethral obstruction occurs more frequently in males than in females. Affected ferrets will often strain to urinate, and in so doing may pass a small amount of soft feces; thus, clients may assume their ferrets are either constipated or have diarrhea. In some cases, ferrets present in a collapsed or weakened state without obvious signs of urinary obstruction. Bladder rupture must be ruled out in these situations.
The differential diagnosis for urethral obstruction includes urolithiasis or crystalluria, gross pyuria, urethral compression due to prostatomegaly or prostatic cysts (in males) or other cystic paraurethral structures (in males or females), or neoplasia (rare). Diagnostic tests include urinalysis, urine bacterial culture and antimicrobial sensitivity testing, radiographs (Fig. 4), and abdominal ultrasound. Ideally, urine collected by cystocentesis should only be attempted after an obstruction has been relieved to prevent leakage of urine or mural compromise of a turgid bladder. The radiodensity of struvite uroliths is variable. Ultrasound will help identify radiolucent uroliths in the bladder, prostatomegaly, prostatic cysts, or other cystic paraurethral structures. It can also aid evaluation of the kidneys, ureters, bladder, and adrenal glands (Fig. 3). Uroliths in the penile urethra can be difficult to detect but may be visualized with contrast cystourethrography. That procedure is also useful in cases of suspected bladder or urethral rupture. In addition to urine testing and imaging, blood should be submitted for a CBC, serum biochemical analysis, and, with debilitated ferrets, blood gas analysis.
Fig. 4Survey radiograph of a 4.5-year-old male castrated ferret with cystic (white arrow) and ureteral (black arrow) calculi.
In cases of urethral obstruction, urethral catheterization should be attempted as soon as possible. Simultaneously, stabilization of metabolic derangements should be initiated. If the urethra cannot be catheterized, a 25-gauge needle can be used to perform cystocentesis and decompress the bladder. However, this procedure should not be performed repeatedly due to risk of compromising the bladder wall. If catheterization still cannot be achieved, temporary cystostomy should be considered. A small Foley catheter can be inserted from the ventral body wall into the bladder to allow direct evacuation of urine (Fig. 5). If the ferret has been stabilized, cystotomy and anterograde flushing of the urethra can be performed. Uroliths should be submitted for analysis.
Fig. 5Temporary cystostomy can be performed on ferrets with urethral obstruction when a urethral catheter cannot be passed. This ferret's urethral obstruction was secondary to prostatic disease. (From Orcutt C. Treatment of urogenital disease in ferrets. Exotic DVM 2001;3(3):31–7.)
]. This procedure will not relieve urethral obstruction due to prostatomegaly. Unilateral nephrectomy may be required in cases of renal calculi to avoid subsequent hydronephrosis, pressure necrosis, or pyelonephritis.
Long-term management of urolithiasis includes conversion to a high-quality, animal protein-based diet. Urinary acidifiers are not necessary if the ferret is eating an appropriate diet. Struvite-dissolving diets (eg, Prescription Diet Feline s/d, Hill's Pet Products, Topeka, KS) are not palatable to ferrets and contain insufficient protein for long-term use [
Prostatic disease has become the most common form of disease affecting the urinary tract of male ferrets seen in this author's practice. Prostatomegaly, prostatic cysts, and prostatic abscesses in ferrets are seen in conjunction with adrenal disease. Excess androgens produced by abnormal adrenal tissue are theorized to stimulate proliferation of prostatic glandular tissue in ferrets [
]. Subsequent prostatic enlargement may result in partial or complete extramural urethral obstruction. Affected prostatic tissue often becomes cystic and inflamed secondary to filling of prostatic acini with keratin, squamous cells, and cellular debris thought to result from estrogen-induced squamous metaplasia [
]. This creates an environment conducive to secondary bacterial prostatitis. Because the prostate communicates with the bladder, the thick purulent material produced can either mimic or induce a bacterial cystitis. In some cases, gross pyuria can result in penile urethral obstruction. Prostatic neoplasia is extremely rare in ferrets.
Clinical signs of prostatomegaly resulting in urethral compression are the same as those with urethral obstruction from any cause. In most cases of prostatic disease, ferrets are over 2 years of age and exhibit accompanying signs of adrenal disease—for example, alopecia, pruritus, a pronounced musky odor, or increased sexual behavior. However, some ferrets show none of these signs. Ferrets with prostatic abscesses may show signs of systemic illness—for example, pyrexia, anorexia, and lethargy. Individuals that are not obstructed but have cystic or bacterial prostatitis may exhibit urine dribbling and preputial dermatitis.
The prostate in the normal ferret is not palpable, but the enlarged prostate is usually palpable as a firm soft tissue mass dorsal to the bladder. In some cases, the prostate is as large as, or larger than, the bladder itself (Fig. 6A). However, some ferrets with prostatitis do not have palpable prostatomegaly. The bladder is enlarged and firm in cases of urethral obstruction.
Fig. 6(A) A 4.5-year-old male castrated ferret presented with an acute onset of stranguria. Abdominal exploratory revealed left adrenomegaly and a markedly enlarged prostate gland (right), which communicated with the smaller bladder (left). (B) A left adrenalectomy was performed, and the prostatic abscess was marsupialized. The probe is inserted into the marsupialization site. Urine culture isolated a heavy growth of E. coli, which was sensitive to cefazolin. After several days, drainage from the marsupialization site stopped, the stoma healed by second intention, and the ferret recovered with no complications. (From Orcutt C. Treatment of urogenital disease in ferrets. Exotic DVM 2001;3(3):31–7.)
Fig. 6(A) A 4.5-year-old male castrated ferret presented with an acute onset of stranguria. Abdominal exploratory revealed left adrenomegaly and a markedly enlarged prostate gland (right), which communicated with the smaller bladder (left). (B) A left adrenalectomy was performed, and the prostatic abscess was marsupialized. The probe is inserted into the marsupialization site. Urine culture isolated a heavy growth of E. coli, which was sensitive to cefazolin. After several days, drainage from the marsupialization site stopped, the stoma healed by second intention, and the ferret recovered with no complications. (From Orcutt C. Treatment of urogenital disease in ferrets. Exotic DVM 2001;3(3):31–7.)
If the urethra is obstructed, the cause must be determined. Prostatic swelling compresses the urethra as it exits the bladder cranial to or within the pelvic inlet, but uroliths or pyuria can cause obstruction anywhere along the length of the pelvic or penile urethra. Abdominal ultrasound allows visualization of the bladder, prostate, and adrenal glands. Imaging can be used to guide aspiration of cystic areas of the prostate, and samples should be submitted for cytology and bacterial culture and antimicrobial sensitivity testing. Urine should also be submitted for analysis and culture.
Urethral obstruction must be relieved as soon as possible and the metabolic condition of the ferret stabilized. Passage of a urethral catheter may be particularly difficult due to prostatic compression of the pelvic urethra. If the urethra cannot be catheterized, an emergency cystostomy may be necessary (see above). Definitive treatment includes abdominal exploratory and adrenalectomy, and, in some cases surgical treatment of the prostate. Elevated androgen levels begin to decrease immediately after adrenalectomy, and some clinicians report that simple cystic prostatic hypertrophy dissipates within a few days postoperatively [
]. In this author's experience, because many cases of prostatitis involve secondary bacterial infection, resolution of prostatomegaly and return to normal urination does not occur this rapidly. In addition to surgical treatment, administration of an antiandrogen may be helpful, because not all of the abnormal adrenal tissue (thus androgenic stimulation) may have been removed surgically. Leuprolide acetate (Lupron Depot, TAP Pharmaceuticals Inc, Deerfield, IL) is a gonadotropin-releasing hormone analog, which has been used in the treatment of prostatic disease in men. In ferrets, the proposed mechanism of leuprolide acetate involves downregulation of GnRH receptors in the pituitary gland and a subsequent reduction in androgen hormone levels produced by the adrenal glands [
]. The recommended dosage of leuprolide acetate (3.75 mg/mL, 30-day depot formulation) is 100 μg/kg intramuscularly every 30 days in ferrets weighing <1 kg and 200 μg/kg intramuscularly every 30 days in ferrets weighing >1 kg [
]. Interestingly, while the use of leuprolide acetate alone in men with benign prostatic hyperplasia decreases prostatic size, it sometimes induces prostatic squamous metaplasia [
Effect of the addition of estrogen to medical castration on prostatic size, symptoms, histology and serum prostate specific antigen in 4 men with benign prostatic hypertrophy.
Adrenalectomy is the surgical treatment of choice for prostatic disease in the male ferret. In cases of prostatic abscesses, some clinicians have reported successful resolution after debulking or removing abnormal prostatic tissue [
]. In this author's experience, surgical resection of abscessed prostatic tissue has resulted in rapid deterioration of the patient's condition due to suspected peritonitis. Omentalization has been effective with small prostatic cysts, but results of treating large prostatic abscesses with omentalization have not been consistent. Instead, this author prefers to treat prostatic abscessation by marsupialization of prostatic tissue to the ventral abdominal body wall (Fig. 6) [
]. This procedure allows for immediate decompression of fluid-filled structures as well as drainage of septic contents out of the abdominal cavity (Fig. 7). The technique is very similar to that described in dogs, but is made easier by the close proximity of the prostate gland to the body wall in ferrets. Only prostatic or paraprostatic tissue, not bladder tissue, should be marsupialized. Drainage of purulent material subsides within several days, and the stoma heals by second intention. This author has seen no postoperative complications subsequent to marsupialization of prostatic abscesses in ferrets.
Fig. 7Marsupialization of prostatic abscesses allows drainage of septic material outside of the abdomen. The marsupialization site heals by second intention once the drainage stops.
The prostate gland should be biopsied and the contents submitted for bacterial culture and antimicrobial sensitivity testing. Treatment with a broad-spectrum antibiotic should be initiated pending culture results. Antibiotics reported to effectively penetrate the prostate gland in dogs include those that are relatively lipid soluble- for example, enrofloxacin (10 mg/kg orally every 12 hours), trimethoprim/sulfadiazine (30 mg/kg orally every 12 hours), chloramphenicol (50 mg/kg orally, subcutaneously, intramuscularly, or intravenously every 12 hours), and clindamycin (6–10 mg/kg orally every 12 hours) [
]. In severe cases, the author has empirically used cefazolin (22 mg/kg intravenously every 8 hours) or enrofloxacin (10 mg/kg every 12 hours, diluted 50:50 with saline and injected slowly intravenously; off-label use) pending culture results. Although some clinicians report that the prognosis is guarded to poor with prostatic abscesses [
], this author has seen complete resolution of signs subsequent to prostatic marsupialization, adrenalectomy, and several weeks of antibiotic treatment.
Cystic urogenital anomalies
Cystic structures can be found near the bladder or the proximal urethra in ferrets of either sex and, in some cases, can grow large enough to cause extraluminal urethral obstruction. Fluid-filled cystic structures of variable size were reported on the dorsal aspect of the urinary bladder in four male and two female ferrets presented to one institution during an 8-year period [
]. All six ferrets had been neutered, and their ages ranged from 2–7 years. Disease of the adrenal gland, ranging from adrenocortical hyperplasia to adrenocortical carcinoma, was diagnosed in five of the six ferrets (the adrenal glands were not examined in the sixth animal), and hemolytic E. coli was cultured from the cystic paraurethral structure and bladder of one of the female ferrets. Although the paraurethral structures were suggestive of prostatic cysts in the male ferrets, the authors of this report hypothesized that the structures alternatively could have been derived from vestiges of the embryologic urogenital system—for example, remnants of the mesonephric or paramesonephric duct. Embryologically, the distal mesonephric duct and urogenital sinus are incorporated into the dorsal wall of the bladder and the proximal urethra in both males and females. Because sexual hormones are known to affect the development of the urogenital system (especially the mesonephric and paramesonephric ducts) both pre- and postnatally, the authors theorized that under certain circumstances, an axis of neutering-adrenal cortical neoplasia-estrogen/steroid hormone elevation could be involved in this syndrome [
]. The structures enlarged with age, and in some individuals, extremely large masses eventually extended into the neck of the bladder. The authors hypothesized that these structures arose by expansion of urethral glands normally present in mink. These glands are not found in female ferrets [
]. However, embryologically, both urethral and prostatic glands are derived from the urogenital sinus. Diagnostic and treatment modalities for large paraurethral cysts are similar to those described for prostatic cysts/abscesses.
Estrogen-induced bone marrow suppression
Estrogen-induced bone marrow suppression was a significant cause of mortality among female ferrets before commercial breeding farms started neutering kits prior to sale at 5–6 weeks of age. Female ferrets that are not bred can remain in estrus throughout the breeding season, during which time serum estrogen levels are elevated. The ferret is reportedly one of the animals most susceptible to the toxic effects of estrogen [
]. The most common clinical signs include petechiae, ecchymoses, pale mucous membranes, and melena. Secondary bacterial infections are less common. Hematologic findings include initial thrombocytosis and leukocytosis at the onset of estrus, progressing to leukopenia, anemia, and profound thrombocytopenia as estrus continues [
]. Splenic extramedullary hematopoiesis is also decreased. In a study of 20 jills in prolonged estrus, severe anemia due to erythroid hypoplasia was rare, and the most common cause of death was hemorrhagic anemia due to thrombocytopenia [
A presumptive diagnosis is often made on the basis of clinical signs and the age and gender of the patient. The differential diagnosis for vulvar swelling in spayed female ferrets includes an ovarian remnant or adrenal disease. An elevated estrogen level due to prolonged estrus is more likely to involve a jill 1–2 years of age, whereas adrenal disease is more common in animals over the age of 2 years [
]. Abdominal ultrasonography is useful in evaluating the adrenal glands and reproductive tract.
The prognosis for ferrets with estrogen-induced bone marrow suppression is poor. Definitive treatment is ovariohysterectomy, but severe thrombocytopenia and anemia preclude this as an initial option. Ovulation must be induced and supportive care provided until the bone marrow begins to function. This can take weeks, and, in some cases, bone marrow suppression is not reversible. Ovulation may be induced by treatment with human chorionic gonadotropin (100 IU intramuscularly repeated 1 week later if vulvar swelling does not resolve in 3–4 days) [
]. Because one of the proposed mechanisms for estrogen suppression of hematopoiesis is inhibition of erythropoietin, treatment with erythropoietin is reportedly not effective [
]. Use of certain antiestrogens, like tamoxifen citrate and clomiphene citrate, is controversial, because some may have estrogenic effects in ferrets [
]. In one report of a ferret with severe estrus-associated anemia, treatment following ovariohysterectomy included a total of 13 whole blood transfusions over 23 weeks, bone marrow transplantation, stanazolol, prednisone, nutritional support, vitamin B supplementation, and antibiotics. The ferret eventually recovered [
]. To avoid estrogen-induced bone marrow suppression, ferrets that are not intended for breeding should be spayed by 6 months of age or prior to the onset of sexual maturity [
]. Infrequently, adrenal tumors can secrete estradiol in amounts high enough to induce hematologic and vaginal cytology changes similar to those described with prolonged estrus [
Retained ovarian tissue appears to be found more frequently in ferrets than other small animals, perhaps because neutering at an early age allows small amount of ovarian tissue to be left behind [
]. Clinical signs include vulvar swelling, alopecia, and other signs of estrogen stimulation, rarely including hematologic abnormalities. In some cases, retained ovarian tissue may become cystic or neoplastic [
]. Most remnants are too small to be visualized by abdominal ultrasound. Administration of hCG (using the protocol listed above under estrogen-induced bone marrow hypoplasia) may decrease vulvar swelling due to an ovarian remnant. Recommended treatment is abdominal exploratory and removal of any retained ovarian tissue. The adrenal glands should be examined at the same time.
Pyometra
Pyometra is rarely seen in pet ferrets. The presentation is similar to that in dogs and cats, and rarely, ferrets may present with signs of estrogen-induced aplastic anemia [
]. Stump pyometra is occasionally seen in ovariohysterectomized ferrets secondary to hormonal stimulation from adrenal disease or retained ovarian tissue [
]. Ultrasound examination usually reveals a fluid-filled structure dorsal to the bladder, which can be difficult to distinguish from a cystic urogenital anomaly. Treatment involves removal of abnormal adrenal tissue or retained ovarian tissue and resection of the uterine stump [
]. Abscessed masses may be marsupialized (Fig. 8).
Fig. 8(A) The surgeon is elevating a cystic mass found dorsal to the bladder (which is to the left of the mass in this photo) in a 3-year-old female spayed ferret that presented with stranguria of 2 days' duration and a swollen vulva. (B) The mass was biopsied and marsupialized, and the enlarged right adrenal gland was removed. Histopathologic examination could not confirm the exact origin of the cystic mass, but a stump pyometra or a cystic urogenital anomaly was suspected. The ferret recovered uneventfully. (From Orcutt C. Treatment of urogenital disease in ferrets. Exotic DVM 2001;3(3):31–7.)
Fig. 8(A) The surgeon is elevating a cystic mass found dorsal to the bladder (which is to the left of the mass in this photo) in a 3-year-old female spayed ferret that presented with stranguria of 2 days' duration and a swollen vulva. (B) The mass was biopsied and marsupialized, and the enlarged right adrenal gland was removed. Histopathologic examination could not confirm the exact origin of the cystic mass, but a stump pyometra or a cystic urogenital anomaly was suspected. The ferret recovered uneventfully. (From Orcutt C. Treatment of urogenital disease in ferrets. Exotic DVM 2001;3(3):31–7.)
Due to retained testicular tissue, young male pet ferrets, assumed to be castrated, may infrequently develop body condition or behavior consistent with a sexually intact male. The most common cause of such behavior changes in male ferrets over 2 years of age is adrenal disease. Normal testicular descent in ferrets is complete at 6 months of age. However, ferrets sold by commercial breeders are neutered at 6 weeks of age, and the testes may not be completely descended into the scrotum by that time [
]. A remaining testicle may subsequently descend and mimic the appearance of a monorchid. In a cryptorchid, only the vaginal sac passes through the inguinal canal. A recent retrospective analysis of 1597 male ferrets between the ages of 6 and 8 weeks revealed a 0.75% incidence of true cryptorchids [
Primary urinary tract neoplasia in ferrets is rare. In a recent retrospective study on neoplastic diseases in ferrets during the period from 1968–1997, primary tumors of the urinary system were found in only 1% of the 574 ferrets examined, and in those, all of the tumors involved the kidneys [
]. Tumor types that have been reported to involve the urinary tract include papillary tubular cystadenoma, transitional cell carcinoma, renal carcinoma, hemangiosarcoma, and lymphoma [
]. In a retrospective study on malignant lymphoma in ferrets (1983–1990), stage IV lymphoma commonly involved hematopoietic tissues, lung, and kidney. It had invaded the kidneys in 8 out of 18 ferrets [
]. In a retrospective study of 4774 ferrets (1968–1997) (27.1% sexually intact females, 22.2% ovariohysterectomized females, 27.2% sexually intact males, 21.5% castrated males, and 2% sex unrecorded), only 2.3% of the 639 tumors recorded involved the reproductive system [
]. Tumors listed included eight ovarian tumors (one granulosa cell tumor, one luteoma, one leiomyoma, one thecoma, one unspecified tumor), one uterine leiomyoma, four testicular tumors (two interstitial cell tumors, two unspecified tumors), and two mammary gland tumors (one serous papillary cystadenocarcinoma, one unspecified tumor). Preputial masses (eg, apocrine gland adenocarcinoma or apocrine cysts) infrequently occur in male ferrets (Fig. 9). These lesions can be extensive, and wide excision may necessitate penile amputation and urethrostomy [
Fig. 9Preputial apocrine gland adenocarcinoma prior to penile amputation and urethrostomy. (From Fisher PG. Urethrostomy and penile amputation to treat urethral obstuction and preputial masses in male ferrets. Exotic DVM 2002;3(6):21–5.)
Improved nutrition and client education have decreased the incidence of certain urinary tract diseases in ferrets. Early neutering programs at commercial breeding farms in the United States have also led to a marked decrease in the incidence of reproductive tract disease, especially estrogen-induced bone marrow suppression. However, the increased incidence of adrenal disease and its secondary effects on reproductive and associated urinary tract tissue presents an ongoing challenge for the clinician working with pet ferrets. Acute and chronic renal failure remain important, though less common, disease entities. It is imperative that the veterinarian working with pet ferrets be aware of the clinical presentation and clinicopathologic abnormalities associated with these syndromes.
References
Weiss C.A.
Williams B.H.
Scott J.B.
et al.
Surgical treatment and long-term outcome of ferrets with bilateral adrenal tumors or adrenal hyperplasia: 56 cases (1994–1997).
Effect of the addition of estrogen to medical castration on prostatic size, symptoms, histology and serum prostate specific antigen in 4 men with benign prostatic hypertrophy.
00023-3&id=gr1.jpg){kind=link}
00023-3&id=gr2.jpg){kind=link}
00023-3&id=gr3a.jpg){kind=link}
00023-3&id=gr3b.jpg){kind=link}
00023-3&id=gr4.jpg){kind=link}
00023-3&id=gr5.jpg){kind=link}
00023-3&id=gr6a.jpg){kind=link}
00023-3&id=gr6b.jpg){kind=link}
00023-3&id=gr7.jpg){kind=link}
00023-3&id=gr8a.jpg){kind=link}
00023-3&id=gr8b.jpg){kind=link}
00023-3&id=gr9.jpg){kind=link}