An 8-year-old 3.1-kg (6.9-lb) spayed female domestic shorthair cat with a history of chronic renal failure and subsequent renal transplantation was referred because of recurrence of azotemia and a suspected mass in the urinary bladder at the ureteroneocystostomy site. As part of the routine screening that precedes transplantation, the recipient and donor cats were evaluated for Toxoplasma gondii–specific IgG antibodiesa; both cats were seronegative (IgG titer < 1:64).
Six weeks after renal transplantation, the recipient cat was examined by the referring veterinarian for follow-up monitoring. The owner reported that the cat was doing well at home, where it lived with 2 other cats, which included the donor cat; all cats were kept indoors. The cat that was not involved in the transplantation had reportedly been seropositive for T gondii at some point prior to the procedure. Serum biochemical analysis revealed moderate azotemia (BUN concentration, 75 mg/dL [reference range, 14 to 36 mg/dL]; creatinine concentration, 5 mg/dL [reference range, 1.0 to 2.5 mg/dL]), and the cat was hospitalized. Results of a CBC performed during hospitalization were unremarkable. After being hospitalized for 3 days, the cat remained azotemic and was subsequently referred to the Veterinary Hospital of the University of Pennsylvania. At the time of admission, the cat was being treated with cyclosporineb (14 mg/kg [6.4 mg/lb], PO, q 12 h), prednisolone (0.5 mg/kg [0.23 mg/lb], PO, q 12 h), enrofloxacin (5 mg/kg [2.3 mg/lb], IV, q 24 h), ticarcillin-clavulanic acid (50 mg/kg [22.7 mg/lb], IV, q 6 h), and famotidine (0.5 mg/kg, IV, q 24 h).
On physical examination, the cat was bright and alert; no clinical abnormalities were detected. Abdominal palpation was not performed. Serum biochemical analysis revealed several abnormalities, including increased concentrations of BUN (101 mg/dL; reference range, 15 to 32 mg/dL), creatinine (5.5 mg/dL; reference range, 1.0 to 2.0 mg/dL), and phosphorus (10.0 mg/dL; reference range, 3.0 to 6.6 mg/dL). Analysis of a sample of urine obtained by cystocentesis revealed isosthenuria (specific gravity, 1.013), pyuria (10 to 20 WBCs/hpf), hematuria (10 to 20 RBCs/hpf), and proteinuria; however, no bacteria were identified on bacteriologic culture of the urine sample. Abdominal ultrasonography revealed a hyperechoic mass at the site of ureteroneocystostomy and lesions indicative of allograft hydronephrosis and hydroureter (Figure 1). Blood flow throughout the renal allograft was confirmed by use of color flow Doppler ultrasonography. Treatment with fluids was initiated via IV administration of an isotonic crystalloid solutionc (5 mL/kg/h). In addition, all medications that the cat was receiving when admitted were continued at the same dosages, except for famotidine, which was discontinued.
Ultrasonogram of a mass in the urinary bladder of an 8-year-old feline renal transplant recipient 6 weeks after transplantation was performed. Mass had dimensions of 2 cm (plus signs and dotted line number 1) × 1 cm (plus signs and dotted line number 2). Histologic examination of the mass revealed Toxoplasma gondii bradyzoite cysts and tachyzoites. Both the donor and recipient cat were seronegative for IgG antibodies against T gondii prior to transplantation. Notice the mass extending into the urinary bladder lumen from the bladder wall.
Citation: Journal of the American Veterinary Medical Association 232, 7; 10.2460/javma.232.7.1010
An exploratory celiotomy was performed the next day. A 1 × 2-cm irregular, necrotic mass was identified extending from the mucosal surface of the urinary bladder at the ureteroneocystostomy site. The ureter was transected, and a new ureteroneocystostomy site was created. The mass was subsequently excised and submitted for histologic examination. The cat recovered in the intensive care unit, and buprenorphine (0.01 mg/kg [0.005 mg/lb], IM, q 6 to 8 h) was added to the treatment regimen.
On the third day after admission, the cat developed abdominal distention. An abdominal ultrasonographic examination performed in the intensive care unit revealed a large amount of effusion. Hematologic analysis performed the same day identified mild anemia (Hct, 25%; reference range, 24% to 45%) and mild metabolic acidosis (pH, 7.30 [reference range, 7.36 to 7.47]; PCO2, 42.2 mm Hg [reference range, 33 to 52 mm Hg]). Additionally, the cat remained azotemic with increased concentrations of BUN (85 mg/dL) and creatinine (2.6 mg/dL) and was hyperphosphatemic (7.2 mg/dL) and mildly hyperglycemic (181 mg/dL; reference range, 67 to 168 mg/dL). The cat remained bright and alert throughout the day and continued to eat and drink. Intravenous administration of fluids was discontinued when the cat dislodged the IV catheter. At that point, treatment with amoxicillin-clavulanic acid (20 mg/kg [9.1 mg/lb], PO, q 12 h) was initiated.
The next morning, the cat was sedated with butorphanol (0.4 mg/kg [0.18 mg/lb], IM) and midazolam (0.3 mg/kg [0.14 mg/lb], IM) in preparation for ultrasoundguided abdominocentesis. Abdominal ultrasonography detected a large amount of anechoic peritoneal effusion, a thickened urinary bladder wall with polypoid masses extending into the lumen, and moderate pyelectasia within the allograft. Abdominocentesis was performed, and 100 mL of serosanguineous fluid was removed. Fluid analysis revealed a transudate containing hemorrhagic and inflammatory components. Aerobic bacteriologic culture of the fluid yielded no growth of organisms. Because of the increasingly aggressive behavior of the cat, axillary temperatures were monitored throughout the day; the cat became pyrexic (axillary temperature, 39.3°C [102.7°F]).
On the fifth day after admission, the cat remained hyperthermic (axillary temperature, 39.6°C [103.2°F]). Results of histologic examination of the mass from the urinary bladder revealed extensive, severe necrotizing pyogranulomatous cystitis with numerous intralesional T gondii bradyzoite cysts and tachyzoites. Blood samples were collected and submitted for serologic assay of T gondii IgG antibodies and whole-blood trough concentrations of cyclosporine. The T gondii IgG titer was considered a positive result at 1:1,024; the cyclosporine concentration was increased at 1,213 μg/L (target therapeutic range, 300 to 500 μg/L). The cat remained alert and was discharged to the owner with instructions to continue administration of amoxicillin-clavulanic acid for 4 weeks. In addition, the dosages of cyclosporine (14.5 mg/kg [6.6 mg/lb], PO, q 12 h) and prednisolone (0.4 mg/kg, PO, q 12 h) were modified, and clindamycin (16 mg/kg [7.3 mg/lb], PO, q 12 h) was added to the treatment regimen.
Six days after the cat was discharged from our facility, the owner returned with the cat and requested that it be euthanatized because of its deteriorating condition. Clinical signs at that time included anorexia, dehydration, and labored breathing. Necropsy revealed approximately 400 mL of serosanguineous fluid in the abdominal cavity of the cat. Gross examination revealed moderate pelvic dilatation of the renal allograft with a thickened (7 mm in diameter) and tortuous ureter. A small area of erosion was detected on the transplanted ureter at the ureteroneocystostomy site. The lungs contained multifocal, pinpoint, firm lesions.
Histologic evaluation revealed chronic, perirenal lymphoplasmacytic and neutrophilic-histiocytic cellulitis with extensive granulation and intralesional T gondii cysts in the renal allograft and ureter. The organism was not detected in any other tissues, including specimens from the lungs, liver, spleen, and CNS. Severe, diffuse, pyogranulomatous cellulitis with necrosis and hemorrhage was detected in the periureteral and pericystic tissues obtained from the urinary bladder at the ureteroneocystostomy site. Severe peribronchiolar interstitial mineralization and mild pulmonary edema were identified in lung specimens.
Discussion
Toxoplasma gondii is an obligate intracellular coccidium for which felids, including domestic cats, are the definitive host.1 Other warm-blooded animals infected with T gondii can serve as intermediate hosts. The most common route of infection in immunocompetent adult cats and humans is ingestion of cysts in the tissue of infected hosts. Minor routes of infection reported in humans include tissue and organ transplantation and blood transfusion.2,3
In cats, T gondii completes the enteroepithelial phase of its life cycle, which results in the shedding of nonsporulated oocysts in feces.1,4 In cats and intermediate hosts, T gondii undergoes an extraintestinal stage of the life cycle, which results in the formation of tissue cysts that likely persist for the lifetime of the host.1,5 When cats are treated with high doses of glucocorticoids, the organisms can emerge from cysts, causing latently infected cats to again excrete oocysts.6 Reactivation of T gondii in humans secondary to immunosuppression is well documented.7,8 Reactivation secondary to immunosuppression has also been reported in cats with concurrent viral infections9 and cats that have undergone renal transplantation10; however, reactivation can take place in immunocompetent cats as well.1,6
Many cats exposed to T gondii do not develop clinical signs, and the development of clinical toxoplasmosis is more common in immunocompromised cats or in kittens than it is in immunocompetent cats.5 Signs associated with clinical toxoplasmosis in cats include anorexia, icterus, fever, uveitis, and neurologic abnormalities.5 The CNS and hepatic, respiratory, and ocular systems are commonly involved.4
Acute toxoplasmosis in cats following renal transplantation has been reported.10 In that report, 3 renal allograft recipients developed acute toxoplasmosis with diffuse interstitial pneumonia. Clinical signs of infection appeared 3 to 6 weeks after transplantation in 2 of the 3 cats and 6 months after transplantation in the third cat. All cats died within 5 days after onset of clinical signs. Histologic examination of tissues identified T gondii cysts in the renal allograft and tachyzoites in the liver and lungs of 1 cat. In the cat reported here, a diagnosis of toxoplasmosis was made 6 weeks after renal transplantation. However, the T gondii cysts and tachyzoites detected were confined to the donor kidney and site of ureteral implantation, which suggested that the allograft was the source of infection. Of interest, both the donor and recipient cats were seronegative for T gondii IgG antibodies prior to transplantation. After the diagnosis of toxoplasmosis was made, the donor cat was not retested for antibodies against T gondii; this donor originated from a presumably pathogen-free colony of cats.
The Veterinary Hospital of the University of Pennsylvania screens cats for T gondii by use of an indirect hemagglutination test for antibodies, which measures IgG titers. According to the manufacturer of the test,a false-negative results can be obtained from the serum of cats with acute, active infection, in which case the IgM titer would be high but the IgG titer would be undetectable.
Although an infected allograft donor is the most likely source of T gondii for the cat reported here, it is also possible that the recipient cat became infected through some other means after renal transplantation. The cat that shared the home with the recipient cat was reportedly seropositive for T gondii at some point prior to the transplantation. Little is known about the role that stress may play in the reactivation of latent T gondii infections in cats. In accordance with the agreement to perform the transplantation, the donor cat was adopted by the owner of the recipient cat. It is possible that changes that resulted from the addition of this cat into the household may have induced stress in the housemates, which may have resulted in reactivation of latent infection in the cat that was not involved in the transplantation. Because the recipient cat was immunosuppressed, it would have been more susceptible to acquiring T gondii when exposed, particularly if the cats shared the same litter box and the seropositive cat was shedding oocysts during the weeks after the transplantation. Whether these were the conditions for the cat reported here is not known.
Blood transfusions are a potential source of T gondii infections in human transplantation patients, although stringent donor screening has greatly reduced the likelihood of this.3 The recipient cat reported here received a blood transfusion in conjunction with the renal transplantation, and the donor was the same cat from which the kidney was obtained. However, given the lack of clinical signs of systemic toxoplasmosis, such as anorexia, fever, or vomiting, hematogenous spread of infection from donor to recipient was unlikely. Although the recipient cat had labored breathing prior to euthanasia, necropsy revealed no evidence of interstitial pneumonia and pulmonary toxoplasmosis that have been detected in other renal transplant recipients.10 The importance of the pulmonary mineralization that was detected in the cat reported here is not known. The mild pulmonary edema detected during necropsy may have been attributable to postmortem changes or may have been secondary to acute respiratory distress syndrome. Abdominal effusion may have also contributed to the increased respiratory effort.
Potential sources of T gondii infection for the cat reported here included transmission via the allograft or blood transfusion, recrudescence of a latent infection, and ingestion of tissue cysts or sporulated oocysts after transplantation. The facility that maintained the pathogen-free colony of cats added testing for T gondii in the serum of recipient and donor cats to its screening protocol for renal transplantation patients in response to a report10 of fatal toxoplasmosis in transplant recipients. This protocol also includes screening of donor and recipient cats for antibodies against FeLV, FIV, and feline coronavirus. According to the findings for the cat reported here, the methods used to detect T gondii antibodies may not be sufficiently sensitive to prevent spread of infection from donors. Improved sensitivity of screening tests would help to minimize additional loss of patients. In addition, preventing exposure of recipient cats to potential sources of T gondii after transplantation by screening other household cats and restricting access of cats to the outdoors where they can encounter infected prey or other sources of T gondii will help minimize the risk of infection.
TPM-TEST, Wampole Laboratories, Cranbury, NJ.
Neoral, Novartis, East Hanover, NJ.
Normosol-R, Abbott Laboratories, North Chicago, Ill.
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