Abstract
A 1000 kg 29-year-old male beluga whale presented with acute anorexia, lethargy, and behavioral changes and was diagnosed with acute renal failure of unknown etiology based on azotemia (BUN= 136 mg/dl [reference range: 47–55 mg/dl]; creatinine = 4.8 mg/dl [reference range 0.8–1.2 mg/dl]) and urinalysis (color - clear yellow, sp. gr. 1.015, protein 2+, blood 3+). No other hematologic or serum biochemical abnormalities were identified and blood and urine cultures were negative for infectious agents. A urine sediment examination revealed numerous renal tubular epithelial cells supporting a diagnosis of acute tubular necrosis (ATN). Intensive fluid administration was performed, both orally and parenterally (IV and SQ) over the next several days, and the whale was given supportive medications including a steroid to address any potential renal inflammation, a diuretic, an antibiotic, and gastric supportive medications. With medical support and intensive fluid infusions, hematologic, serum chemistry, and iStat values worsened to include a stress leukogram (neutrophils = 5.7 X 103/mm3 [reference range: 3.3–4.9 X 103/mm3]; lymphocytes = 0.5 X 103/mm3 [reference range: 0.7–1.7 X 103/mm3]), hyperkalemia (K = 7.6 mmol/L [reference range: 3.3–4.3 mmol/L]), hyperphosphatemia (P = 10.5 mg/dl [reference range: 4.6 – 6.2 mg/dl], acidosis (pH = 6.99 [reference range 7.35–7.45], and worsened azotemia (BUN = 177 mg/dl; creatinine 11.8 mg/dl), and the animal began to vomit regularly. Metoclopramide was administered and dialysis was considered necessary. Due to the whale's large size and the anticipated difficulty in providing prolonged hemoaccess, hemodialysis was not a rational choice. A previous attempt at peritoneal dialysis in a pilot whale had been unsuccessful and this was not attempted; however, intestinal dialysis was considered reasonable. Based on extrapolation from human therapy, 30 liters of 20% mannitol PO via orogastric tube and replacement of fluid with 100 liters of parenteral fluids supplemented with bicarbonate would be required each day; however, the realistic and tolerated mannitol dose employed was 10 liters orally per day accompanied with 30 liters of parenteral fluids. Over a 15 day period, a clinical improvement was noted in the whale's demeanor and activity level, the vomiting stopped, and changes in chemistries were as follows:
Intestinal dialysis in a Beluga whale.
|
day 1
|
day 4
|
day 7
|
day 10
|
day 13
|
day 15
|
BUN
|
186
|
180
|
160
|
140
|
140
|
136
|
Creatinine
|
13.3
|
14.5
|
14.7
|
16.6
|
18.3
|
19.4
|
Potassium
|
6.9
|
6.1
|
4.8
|
4.4
|
4
|
4.1
|
HCO3
|
10.3
|
14
|
17.5
|
25.4
|
27.2
|
29.4
|
pH
|
6.99
|
7.04
|
7.08
|
7.22
|
7.32
|
7.38
|
Calcium
|
8
|
8.9
|
9.2
|
9
|
9.1
|
9
|
Phosphorus
|
10.4
|
11.8
|
11.1
|
10.4
|
10.3
|
9.5
|
The intestinal dialysis was successful at decreasing BUN and potassium levels and at reversing the acidosis. Consistent with previously described reports in humans undergoing intestinal dialysis, removal of creatinine did not occur; however, the resultant elevations were considered non-toxic.
Despite apparent success in the dialytic goals, the whale expired 15 days into the mannitol treatments. Gross necropsy showed 40 liters of serosanguinous fluid in the abdomen, dark brown urine, and foci of hemorrhage in the connective tissue, muscle, and multiple organs. Histopathology confirmed acute tubular necrosis but failed to conclude a definitive cause of death; however, a contributing factor may have been widespread bleeding secondary to alterations in clotting consequent to the uremia. Normal lungs support that there was no fluid overload present. Electron microscopy showed mild vacuolation of the renal tubular epithelium that could be consistent with osmotic nephrosis. The principal cause of the acute tubular necrosis was not identified; however, there was no evidence of an infectious or inflammatory injury, no aberrant values in catecholamines, and toxicologic testing of the tissues and urine revealed no toxicoses.
We conclude that, despite this whale's death, intestinal dialysis appears to be a reasonable option in providing renal replacement therapy for cetaceans, and should be considered for future cases of acute renal failure.
Acknowledgements
The authors wish to extend their gratitude to Dr. Salvatore Frasca, Jr. of the University of Connecticut Department of Pathobiology and Veterinary Science for his intensive efforts on the pathology. We also thank Dr. Kathy Deering of the University of Connecticut, Dr. Michael Kashgarian of the Yale University Department of Pathology, Dr. Judy St. Leger of SeaWorld San Diego, Dr. Harold Yamase of the University of Connecticut Health Center, and Dr. Tracy Romano from Mystic Aquarium for their extensive consultations throughout the pathologic investigation. We would further like to acknowledge the medical consultations and support we received from Drs. Todd Schmitt and Scott Gearhart of SeaWorld and Drs. Karen Wolf and Allison Case from Point Defiance Zoo & Aquarium. We thank Drs. Tracy Romano, Lisa Mazzaro, and Tracey Spoon for supporting the catecholamine and stress hormone evaluation, and Dr. Lisa St. Aubin for helping in a relief capacity during this time.