Abstract

Evaluation of glomerular filtration rate (GFR) is an important clinical tool for determining the prognosis of chronic renal failure as it reflects renal function.² Among current methods generally available for evaluating GFR, urinary clearance of inulin is considered the gold standard approach however this technique is time consuming and labor intensive.^2,3 As an alternative, iohexol clearance rates have been found to correlate closely with GFR in feline and canine patients with normal to moderately decreased renal function when properly corrected.^1,3,4,5 Given that renal dysfunction in association with Leptospira sp. infection and neoplasia are common in stranded California sea lions (Zalophus californianus) the development of a useful prognostic indicator for these animals would have direct application to their treatment and rehabilitation.^6,7

To develop this method in California sea lions, eight clinically healthy animals and one with evidence of renal compromise (moderately elevated serum blood urea nitrogen and creatinine values) were anesthetized using isoflurane alone or in combination with midazolam (0.15mg/kg) and butorphanol (0.15mg/kg), and administered iohexol (Omnipaque®, Amersham Health Inc., Princeton, New Jersey 08540) at a dose of 300 mgI/kg i.v. Blood samples were collected from the subclavian vein at 2, 3 and 4 hours post iohexol injection, intervals recommended for feline and canine patients, and serum levels of iodine were determined and normalized to body weight to determine GFR.^1,2,3,4,5

The mean (+/- SD) GFR for healthy sea lions anesthetized with isoflurane (n=4) was 5.24 (+/-1.46) ml/min/kg. The mean canine and feline GFRs have been determined by iohexol clearance as 5.48 ml/kg/min and 1.94 ml/kg/min respectively.^1,2,5 Of note, glomerular filtration rates could not be determined in sea lions administered midazolam-butorphanol-isoflurane, which included the sea lion with renal compromise, due to non-linearity in the β- or elimination-phase. The preliminary data may indicate that changes in GFR in California sea lions are not directly comparable to those of canine and feline populations because of morphologic and physiologic adaptations in marine mammals that influence renal vascular function, especially under anesthesia.

Additional data are currently being evaluated from a further two healthy yearling sea lions anesthetized with isoflurane alone then administered iohexol at the dose described above. These animals were sampled more frequently to determine the iohexol distribution and elimination curve in sea lions, and thus the most appropriate compartment model for rate calculation and the timings for sample collection in this species. The determination of normal GFR ranges for sea lions will not only enhance clinical prognosis following insults such as leptospirosis, but may influence development of species-specific therapeutic drug dosages and advance understanding of toxic effects of compounds undergoing renal excretion.

Acknowledgements

The veterinary staff and volunteers at The Marine Mammal Center, Sausalito, CA; Dr. Wilson Rumbeiha and staff at the Toxicology Section, Diagnostic Center for Population and Animal Health, Michigan State University, Lansing, MI. Funding for this study was provided by the Arthur and Elena Court Nature Conservancy, and Mrs. S. Sichel.

References

1.  Brown SA, Finco DR, Boudinot FD, Wright J, Tarver SL, T Cooper. 1996. Evaluation of a single injection method using iohexol for estimating glomerular filtration rates in cats and dogs. AJVR 57:105-110.

2.  Finco DR, Braselton WE, TA Cooper. 2001. Relationship between plasma iohexol clearance and urinary exogenous creatinine clearance in dogs. J. Vet. Intern. Med. 15(4):368-73.

3.  Finco DR. 2005. Measurement of glomerular filtration rate via urinary clearance of inulin and plasma clearance of technetium Tc 99m pentate and exogenous creatinine in dogs. Am. J. Vet. Res. 66(6):1046-1055.

4.  Gaspari F, Perico N, Ruggenenti P, Mosconi., Amuchastegi CS, Guerini E, Dainia E, G Remuzzi. 1995. Plasma clearance of non-radioactive iohexol as a measurement of glomerular filtration rate. J. Am. Soc. Nephrol. 6:257-263.

5.  Goy-Thollot I, Chafotte C, Besse S, Garnier F, PY Bartez. 2006. Iohexol clearance in healthy dogs and cats. Vet. Radiol. Ultrasound 47:168-173.

6.  Gulland FM, Koski M, Lowenstine LJ, Colagross A, Morgan L, T Spraker. 1996. Leptospirosis in California sea lions (Zalophus californianus) stranded along the central California coast, 1981-1994. J. Wildl. Dis. 32:572-80.

7.  Gulland FM, Trupkiewicz JG, Spraker TR, LJ Lowenstine. 1996. Metastatic carcinoma of probable transitional cell origin in 66 free-living California sea lions. J. Wildl. Dis. 32(2):250-258.