Abstract
A 36-year-old female Asian elephant (Elephas maximus) housed at the National Zoo was presented for hematuria, followed by progressive lethargy and anorexia.
Keepers initially described the elephant as restless and repeatedly stretching the hind limbs. A small amount of dark-colored urine was voided. On the following day, the elephant developed obvious hematuria confirmed by reagent strips for urinalysis (Multistix, Bayer Corporation, Elkhart, IN, USA), accompanied by lethargy. On physical exam, the elephant had dry mucous membranes, thick saliva, and mild tachycardia (60 bpm), suggestive of mild dehydration. Blood was collected from the aural vein and the hemogram revealed leukopenia (6.7×103/µl of neutrophilia (5.0×103/µl) with a left shift (0.1×103/µl bands), and monocytopenia (0.938×103/µl).1,2 Free-catch urinalysis confirmed hematuria and revealed moderate leukocyturia, although no bacteria were seen. Urine sediment cytology revealed numerous red blood cells (RBC), prominent cellular casts containing neutrophilic and epithelial cells remnants. History review revealed that the elephant was receiving ibuprofen (Schein Pharmaceutical, Inc., Florham Park, NJ, USA; 1.2 mg/kg PO SID) over the previous 3 years for chronic lameness due to historic ankylosis of left carpus. Initial differential diagnosis included acute tubular necrosis, cystitis, and bacterial or toxic pyelonephritis. The ibuprofen was discontinued and sucralfate (Teva Pharmaceuticals, Sellersville, PA, USA; 15 mg/kg PO SID for 7 days) was administered for presumed gastrointestinal ulceration. The elephant was then started on oral sulfamethoxazole/trimethoprim (TMS, Teva Pharmaceuticals; 15 mg/kg PO SID for 7 days). This antibiotic was chosen for its palatability and once-daily dosing regimen. The elephant was offered a variety of enteral fluids (water, sport drink, juice) to prevent further dehydration and encourage diuresis.
The elephant’s attitude had improved by the next morning. Water consumption and appetite was normal for all items except concentrates. However, the hematuria had worsened and azotemia developed (BUN 15 mg/dl, creatinine 2.5 mg/dl).1,2 By the third day, she was completely anorectic, depressed, dehydrated, and azotemia had progressed: BUN 19 mg/dl, creatinine 3.4 mg/dl. Repeated urinalyses revealed progressive hematuria, severe leukocyturia, isosthenuria, proteinuria, and numerous granular casts, free tubular cells, and endothelium. Streptococcus zooepidemicus was isolated from urine culture free catch that was resistant to TMS. A diagnosis of acute bacterial pyelonephritis was made. The elephant was not drinking, and it was clear that the hydration status was rapidly declining.
Two 14-G, 2-inch catheters were placed in left auricular veins, sutured, and then glued to the skin. These catheters were lavaged every 2 hours with heparin (Hep-Lock, Elkins-Sinn, Inc., Cherry Hill, NJ, USA) for 72 hours. Ceftiofur (Naxcel, Pharmacia & Upjohn Company, Kalamazoo, MI, USA; 6 g IV and IM TID) and intravenous fluids were initiated. The calculated fluid therapy volume for maintenance alone was 120 L (40 ml/kg/day). Less than half of this requirement was provided on day 1 of fluid therapy (54 L of crystalloids IV in two sessions), yet the elephant’s attitude improved towards the end of the day.
Four days after initial presentation, the elephant dramatically declined in the afternoon with profound lethargy becoming somnolence. Chemistry panel was unchanged from prior azotemia, but the hemogram showed a leukocytosis (12.2×103/µl). Cytologic evaluation of urinalysis revealed gram-positive cocci and gram-negative rods within tubular casts. To supplement intravenous fluid therapy of 40 L TID rectal hydration was added as 50 L of water divided into eight enemas throughout the day. The elephant had improved attitude and appetite, and, by the fifth day after presentation, began to resist fluid administration. Therefore, intravenous fluids (in two 40-L sessions) plus 40 L rectally were provided. Urine sediment cytology was suggestive of improvement of the kidney based upon minimal cylindruria, fewer RBC, and increased number of macrophages.
The following day, the elephant’s appetite and water consumption were markedly improved. A final intravenous fluid supplement (40 L) was provided before the catheters were removed. Hydration therapy was maintained using rectal fluids (20 L). Because the elephant now objected to intramuscular antibiotic therapy, intravenous ceftiofur through the aural veins was continued. However, the next day, bilateral nictitating membrane inflammation and oral cavity mucous membrane hyperemia developed from a possible drug reaction to ceftiofur. Despite discontinuation of antibiotic, the elephant passed unformed stools that were attributed to gastrointestinal microfloral imbalance from the antibiotic.
Although the attitude and food consumption in this animal were rated as normal after an additional five days, the hemogram revealed leukocytosis (WBC 32.2×103/µl) and urine had low numbers of RBC and WBC, plus occasional cylindruria, bacteria, epithelium, and tubular cells were confirmed on urinalysis. The elephant was continued on oral antibiotics (Cephalexin, Novopharm USA, Inc., Schaumburg, IL, USA; 5 g PO BID for 6 weeks. During this treatment interval, urinalyses continued to reveal variable numbers of RBC, a declining number of WBC, trace bacteria, and casts. Given the possibility of a low-grade persistent pyelonephritis or cystitis, antibiotic therapy was switched to enrofloxacin (Baytril, Bayer Corp., Shawnee Mission, KS, USA: 10 g PO BID for 4 weeks). During the subsequent three months, urinalyses continued to reveal variable numbers of RBC, but serum chemistry and hemograms returned to within the normal range.
To date, 1 year after treatment, the elephant remains clinically normal. Urinalyses are performed twice per week and minimal numbers of RBC and occasional WBC are present. The original cause of the pyelonephritis of this elephant was not elucidated. However, an ascending bacterial infection from the urinary or reproductive systems cannot be ruled out.
Acknowledgments
The authors want to acknowledge: the staff at the Elephant House as the positive outcome on this case would not have been possible without their skills and effort, consulting veterinarians, Dr. D. Schmitt, Dr. P. Anakis, Dr. Th. Hildebrandt, Dr. F. Göritz, and Dr. R. Hermes for their assistance, and the Clinical Pathology Laboratory staff at the NZP for their invaluable work that helped to diagnose and treat this case.
Literature Cited
1. International Species Information System. 1999. Physiological Reference Values for Elephas maximus, Females, >30 years. International Species Information System, Apple Valley, Minnesota.
2. Clinical Laboratory, Department of Pathology, Smithsonian National Zoological Park. 2002. Normal Hematological Values for this elephant (1989–2002).