Abstract

Renal failure is a major cause of morbidity and mortality in the captive cheetah population.^8,10 Specifically, there are high prevalences of glomerulosclerosis (82%) and renal amyloidosis (38%) with lesions seen in cheetahs as young as 1 year old.^3,10,11 Because renal disease limits the viability of the captive cheetah population, early diagnosis and therapy may be beneficial to prolong and improve the quality of life for affected captive cheetahs.

Serum concentrations of blood urea nitrogen (BUN) and creatinine are insensitive indicators of renal damage.⁵ With renal damage, increased flow of fluid and filtered protein in remaining tubules results in solute loss. The net effect is an increased clearance of electrolytes relative to creatinine. Fractional excretion and urine protein:creatinine ratios have been evaluated for diagnosis of renal damage in domestic cats.^1,4,6,7,9,12 The urine protein:creatinine ratio and fractional excretion of sodium, chloride, potassium, calcium, and phosphorus have been shown to increase in domestic cats with chronic renal disease.^1,2,4 The purpose of this study was to determine if fractional excretion tests could reliably diagnose renal damage earlier than elevated serum BUN and creatinine in cheetahs.

Paired urine and serum samples were obtained from 13 healthy cheetahs (7.6) and six cheetahs with renal disease (2.4) during annual physical exams. A minimum of two sequential samples were obtained from each animal. Cheetahs were maintained at White Oak Conservation Center and fed a commercial ground horse meat-based diet (Nebraska Brand Canine Diet; Central Nebraska Packing Co., North Platte, NE) supplemented weekly with ox tails. Water was available ad libitum. Cheetahs were anesthetized, and urine was obtained by sterile catheterization. Urine and serum were stored frozen (-70°C) until analysis. Urine and serum chemistries were measured at a commercial laboratory.

Fractional excretion (FE) of electrolytes was calculated using the following formula:

The ratio of urine protein to urine creatinine was also calculated.

Cheetahs that never developed persistently elevated BUN/creatinine over the 4 years of the study were classified as normal. Abnormal cheetahs had at least one sample point in which BUN/creatinine were normal but developed persistently elevated BUN/creatinine during the study period. A comparison of the accuracy of diagnostic tests generally requires an independent gold standard. Because there is no reasonable independent gold standard available for diagnosing renal disease in cheetahs, the result of outcome serves as the gold standard.

There was a significant difference (p<0.05) between values from normal and abnormal cheetahs for all tests. Normal ranges were calculated using mean and 2 SD and are shown in Table 1. The maximum test efficiency (accuracy) was calculated for each test at the time of diagnosis of renal disease and 1 year prior to diagnosis. All of the tests evaluated had high levels of accuracy for early diagnosis of renal disease. Sensitivity, specificity, and predictive values (data not shown) were also >80% for most tests. Relative to the other tests, the low accuracy of the urine protein:creatinine ratio was probably the result of placing all abnormal cheetahs in the same group regardless of disease etiology. All of the abnormal cheetahs with glomerulosclerosis confirmed by histopathology had increased urine protein:creatinine ratios.

Table 1. Normal range and accuracy of fractional excretion tests and urine protein:creatinine ratio for diagnosing renal damage at the time of diagnosis by increased BUN/creatinine and 1 year prior to abnormal BUN/creatinine

The use of fractional excretion tests has been limited in domestic cats, because values are affected by diet and time of day in addition to renal status. Because most cheetahs in captivity receive a similar diet and are fasted prior to annual physical exam, this dietary limitation of fractional excretion tests is minimized. In this study, fractional excretion tests were able to diagnose renal damage earlier than serum BUN and creatinine elevation. Further research is needed to evaluate the potential of fractional excretion tests to differentiate between glomerulosclerosis and renal amyloidosis.

Acknowledgments

The authors wish to thank Cyd Shields Teare, Kelly Hernandez, and Lisa Kolbach at White Oak Conservation Center for their assistance with sample collection and analysis. We would also like to thank Dr. Linda Munson for histological examination of kidneys.

Literature Cited

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