Diagnosis and Treatment of Acute Renal Failure in an Eight-Month-Old Giant Panda (Ailuropoda melanoleuca)
This report describes acute renal failure in an eight-month-old female giant panda (Ailuropoda melanoleuca). Acute renal failure was diagnosed following an episode of gastrointestinal signs. An elevated blood urea nitrogen (BUN) was present on bloodwork and renomegaly was evident on palpation as well as on ultrasound examination. Kidney biopsy revealed marked tubular necrosis, mineralization, and dilatation. Scintigraphy revealed poor renal function. Her condition improved following a period of intensive therapy; however, she died five months later. Main gross pathologic changes included renal calcification, liver enlargement, pulmonary edema, gastrointestinal hemorrhage, and mandibular bone deformity.
A female giant panda was born in August of 1999 at the China Research and Conservation Center for the Giant Panda (CRCCGP) in the Wolong Nature Reserve, Sichuan Province, China. Her dam had given birth to triplets and she was raised through a combination of hand-rearing and maternal care up to six months of age. The panda was removed from her dam on 20 February of 2000 as part of a standard protocol to encourage adult females to come into estrus in the spring. Her body condition was not as good as other cubs and she tended to have more problems during this time.
The panda developed diarrhea in mid-March. She was treated with antibiotics, including gentamicin, and the diarrhea resolved. At the beginning of April, she had an episode of decreased activity, diarrhea, and vomiting which resolved within 48 hours. On 9 April she looked uncomfortable, had vomiting, loose stools, serous nasal discharge, and pruritus. She was treated for suspected respiratory and gastrointestinal disease for three days. There was little response to therapy. A blood sample was obtained on 13 April. Her BUN was greater than 140 mg/dl and she was acidotic. A hand-held chemistry analyzer was used; therefore, only a limited number of chemistries were available. On 14 April she was noted to have many small red macula on her skin as well as hair loss and continued pruritus. She was anesthetized for fluid therapy four times during 14–18 April. Physical examination revealed enlarged kidneys on abdominal palpation. Ultrasound examination confirmed renomegaly as well as ascites. Her condition improved following intravenous fluid therapy and therapy was discontinued after 18 April. On 24 April, the panda had vomiting, diarrhea, and was weak. She had developed significant alopecia on her head and abdomen by this time.
The animal was transferred to the People’s Hospital of Sichuan in Chengdu for more aggressive diagnostics and treatment. Renal scintigraphy, renal biopsy, and repeat ultrasound examinations were performed there. Kidney biopsy revealed marked tubular necrosis, mineralization, and dilatation. Tubular basement membranes generally appeared to be intact. Remaining non-necrotic tubules were lined by attenuated or hyperplastic, regenerating epithelium. Bowman’s spaces were often dilated, and some glomeruli were small and atrophic. The interstitium was moderately to markedly expanded by edema, with mild accompanying fibrosis. Ultrasound examination reconfirmed bilateral renomegaly. The left kidney measured 8.4×6.4 cm. The right kidney measured 7.5×5.0 cm. These values were thought to be about twice the size of a normal kidney for an animal this age. Scintigraphy revealed reduced renal perfusion as well as reduced urine production. In addition to elevations in her BUN and creatinine she was also anemic. Urinalysis revealed a specific gravity of 1.004 (normal range: 1.015–1.028) as well as glucosuria and mild proteinuria.
The treatment plan consisted of intravenous fluid therapy, improving immune function, controlling secondary infections, improving renal circulation, treating the anemia, and adjusting her nutrition. She was treated initially with daily intravenous fluids. As her condition stabilized, intravenous fluids were administered every two days. Her appetite, activity, and fecal consistency gradually improved though she was still weak relative to a normal juvenile giant panda. A second scintigraphy procedure was performed. Renal perfusion and urine production were improved. Her BUN returned to slightly higher than normal level; however, her creatinine remained elevated (7.68–6.49 mg/dl).
After 20 days at the People’s Hospital, the panda was returned to CRCCGP in Wolong. Her bloodwork was monitored every other day for the next two months. Urinalyses were performed daily. Because she was eating and her bloodwork was relatively stable, fluid therapy was not continued. During this time (as well as when she was at the People’s Hospital) she was treated with Chinese caterpillar fungus mixture, Ketosteril, Epiao, as well as oral vitamins and iron supplements. Chinese caterpillar fungus mixture is used frequently in people in China to improve immunity and renal function. Ketosteril is a Chinese medicine containing amino acids (isoleucine, leucine, phenylalanine, methionine, L-lysine, L-threonine, L-tryptophan, L-histidine, L-tyrosine) used to treat renal disease. Epiao is similar to erythropoietin. The dose of Epiao was 75 IU/kg twice weekly. Her anemia initially improved during the first month of treatment but became ineffective during the second month of treatment and was discontinued.
During the next several months her condition was fairly stable. While her vitality improved, it was below that of a normal juvenile giant panda. She had several episodes of gastrointestinal disease as well an episode of respiratory disease in September. During this time her BUN ranged between 18–36 mg/dl. Creatinine levels continued to be greater than 5 mg/dl. The anemia persisted. Her condition started to deteriorate in October. She developed severe abdominal distension, diarrhea, decreased activity, poor appetite, and hair loss. On October 19th, she developed acute hemorrhagic gastroenteritis and anorexia. She did not respond to treatment and she died on 21 October.
At necropsy the main pathologic changes were observed in the kidneys, liver, gastrointestinal tract, and mandibular bone. Both kidneys had extensive calcification. Little normal renal tissue was present. The liver was enlarged; liver weight was 1220 g (normal adult liver weight at necropsy ∼875 g). Severe mucosal hemorrhage was observed in the stomach and intestines, especially in the duodenum. The mandible was shorter than the maxilla. Pulmonary edema was also present. Histologic examination of tissues is pending.
This is the first time a case of acute renal failure in a juvenile giant panda has been described. The panda’s clinical signs prior to death are compatible with renal failure. While the exact cause is unknown some differentials include congenital disease, toxic insult, immune-mediated, or an infectious etiology.
One of the panda’s siblings died at two days of age. It was the smallest of the triplets and was suspected to have a congenital problem involving the urinary system based on gross necropsy evaluation. The third triplet currently has higher creatinine and BUN values, and its body condition is not as good compared to other juvenile giant pandas. However, changes consistent with a congenital problem were not evident on the kidney biopsy. Renal failure secondary to gentamicin toxicity is another possibility. This cub received only one dose. Gentamicin has been used frequently at CRCCGP in other young giant pandas without problems. It is possible that this female already had an underlying condition making it more susceptible to gentamicin toxicity such as the episode of gastrointestinal signs prior to developing acute renal failure. Cubs are given access to an outside exercise yard for periods during the day. The panda was observed on occasion eating dirt as well as some wild plants. It is possible that she ingested a toxic compound via this route. No evidence of an infectious agent was seen on the kidney biopsy. Cultures were not performed due to limited diagnostic availability at CRCCGP. It is possible that her episode of vomiting and diarrhea prior to the onset of acute renal failure predisposed her to renal insult. The skin lesions noted are of interest; however, diagnostics were not performed. It is not known at this time if and how these lesions are related to the renal disease.