Determination of Glomerular Filtration Rates in Clinically Healthy California Sea Lions (Zalophus californianus) Using Iohexol Clearance Rates
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.
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.
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