Lethargy and vomiting were observed in a 4-yr-old female cheetah at the National Zoological Park (NZP) on the morning of 9 November, 1996. Later in the day the animal appeared brighter and subsequently ate half of its normal diet. The next day the cheetah was alert and responsive but anorexic. On 11 November, its condition had significantly worsened. The cheetah was unable to stand, severely depressed, and polyuric. Physical examination revealed mild dehydration and severe, bilateral renomegaly. Complete blood count and serum chemistry analysis demonstrated mild anemia (hematocrit 37%) and severe azotemia (blood urea nitrogen 230 mg/dl, creatinine 12 mg/dl, phosphorus 14.6 mg/dl). Urinalysis was unremarkable (specific gravity 1.016 g/dl, pH 6.0). Radiology and transabdominal ultrasonography confirmed that both kidneys were markedly enlarged. In addition, there was increased renal cortical echogenicity and loss of corticomedullary definition. A percutaneous renal biopsy was obtained from the left kidney. Pending histopathology, the presumptive diagnosis was toxin-induced acute renal failure.
The cheetah improved clinically in response to initial therapy (intravenous and subcutaneous fluid therapy, cephalothin, ranitidine). The animal continued to produce urine and accepted oral medicines the following day (aluminum hydroxide, omeprezole, cephalexin). However, severe azotemia (BUN 290 mg/dl, creatinine 26 mg/dl) was evident upon repeat examination on 13 November. Biopsy results revealed severe acute tubular degeneration associated with birefringent crystals typical of calcium oxalate. These findings were considered characteristic of ethylene glycol toxicity.1,3,5
Although prognosis was extremely poor, the cheetah was alert and active. Uremic signs were limited to the gastrointestinal tract (vomiting, diarrhea). The animal was hospitalized for continuous fluid therapy and supportive care, including total parenteral nutrition (TPN) and whole blood transfusion. Hemodialysis was considered at this time, but the technical demands and potential complications of the procedure were judged to be excessive. Fluid and diuretic therapy over the next several days was successful in promoting diuresis. The animal’s strength improved on TPN, which was designed to limit protein (1.5 g/kg) and to deliver 50% of its daily caloric requirement each as lipid and dextrose. After 5 days the animal regained its appetite and readily consumed small amounts of lamb and turkey (lower protein relative to the commercial horsemeat diet.) However, the next day, the ingestion of even a single piece of meat produced signs of renal encephalopathy (e.g., vision loss, stupor, seizures). Hemodialysis was attempted on 20 November, but the cheetah died of complications during the procedure.
Necropsy results confirmed the diagnosis of renal oxalosis: there was marked tubular degeneration and regeneration associated with massive numbers of birefringent crystals in the tubular lumen. The crystals were proven to be the monohydrate form of calcium oxalate using infrared microspectroscopy and a laser Raman microprobe.6
The following were considered potential causes of renal oxalosis in this cheetah: ingestion of 1) food contaminated with ethylene glycol (either inadvertent or malicious), 2) an ethylene glycol-containing chemical (e.g., antifreeze, photographic chemicals, brake fluid), or 3) oxalate containing plants.1,3-5,7,8 Chemical exposure was highly unlikely given that there was no vehicle access to the cheetah holding areas or yards. While a sparse number of oxalate-containing plants were growing in the exhibit, no cheetah was ever observed to eat these, or other, plants. Therefore, contaminated food was considered the most likely source. This poisoning was either an act of vandalism (the cheetah was hand-reared and could have accepted the toxin in food from the public), or the commercial horsemeat diet contained the chemical. There is precedent for accidental contamination of zoo felid diets with ethylene glycol.4,7,8 In 1978, several felids from various zoos died from renal oxalosis.4,8 The source was traced to a faulty machine at the meat processing plant but only after several months of testing multiple batches of diet (M.K. Stoskopf, personal communication).
In domestic dogs and cats, ethylene glycol toxicity is almost exclusively the result of antifreeze ingestion. Unless treated specifically within 24 hr of exposure (4-methylpyrazole or ethanol, sodium bicarbonate) this condition is usually fatal, even if the animal survives the induction phase and enters the maintenance phase of acute renal failure.3 At this stage, the prognosis depends largely upon the severity of uremic signs (e.g., anemia, platelet dysfunction, gastritis, encephalopathy) and the success of supportive care, which requires months of therapy to allow the tubules time to regenerate and regain function. Although hemodialysis offers the best chance of survival, it requires special equipment and repeat treatments (2–4 hr of diuresis a day for the first week, then two to three times weekly to maintain acceptable BUN and creatinine levels).2 During the session, the patient must remain stationary with the heart maintained at the level of the mechanical kidney in the dialysis machine. In a cheetah this would have required repeated sedation and long-term catheterization.
The source of ethylene glycol in the NZP cheetah case was never identified. Analyses were performed at the Animal Health Diagnostic Laboratory at the Michigan State University College of Veterinary Medicine (East Lansing, MI, USA). Representative samples from the commercial horsemeat-based diet were negative for both ethylene glycol and oxalates. Beet pulp (used as a filler in this product) samples provided by the manufacturer were also analyzed for oxalates and found to contain minimal amounts. Blood and urine from the cheetah were also negative for ethylene glycol. This finding was not surprising given that the samples were obtained at least 72 hr following initial exposure.3,5 No illness developed in the cheetah that consumed meat from the same package as the affected cheetah. However, once the diagnosis was confirmed, all NZP felids were placed temporarily on a nutritionally complete all beef diet. A new vendor was subsequently identified and all of the felids were switched to the new, nutritionally balanced, horsemeat-based product.
The authors wish to thank Mark Berkowicz, DVM, and staff from Veterinary Referral Associates, Gaithersburg, MD, for providing the hemodialysis equipment and technical expertise, and Jose A. Centeno, Ph.D., from the Department of Environmental and Toxicologic Pathology, Armed Forces Institute of Pathology, Washington, DC, for microspectroscopy.
1. Adams, W.H. 1984. Ultrasonographic findings in dogs and cats with oxalate nephrosis attributed to ethylene glycol intoxication: 15 cases (1984–1988). J. Am. Vet. Med. Assoc. 492–496.
2. Cowgill, L. and C.E. Langston. 1996. Role of hemodialysis in the management of dogs and cats with renal failure. Vet. Clin. N. Am.: Sm. Anim. Prac. 26(6): 1347–1378.
3. Grauer, G.F., and I.F. Lane. 1995. Acute Renal Failure. In: Ettinger, S.J., and E.C. Feldman (eds.). Textbook of Veterinary Internal Medicine, W.B. Saunders Co., Philadelphia. 1720–1733.
4. Kitchen, H., W. Shipman, and D. Black. 1978. Oxalate toxicosis in captive large felids. Proc. Am. Assoc. Zoo Vet. 270–275.
5. Nicholson, S.S. 1995. Toxicology. In: Ettinger, S.J., and E.C. Feldman (eds.). Textbook of Veterinary Internal Medicine, W.B. Saunders Co., Philadelphia. 317–318.
6. Pestaner, J.P., F.G. Mullick, F.B. Johnson, and J.A. Centeno. 1996. Calcium oxalate crystals in human pathology: molecular analysis with the laser Raman microprobe. Arch. Pathol. Lab. Med. 120:537–540.
7. Silberman, M. 1977. Antifreeze (ethylene glycol) poisoning in a captive cheetah (Acinonyx jubatus) population. Proc. Am. Assoc. Zoo Vet. 154–161.
8. Stoskopf, M. K., J. D. Strandberg, and F. M. Loew. 1978. Renal oxalosis in large felids maintained on a commercial diet. Proc. Am. Assoc. Zoo Vet. 154–161.