Abstract

Clinical diagnosis of kidney disease in California sea lions (Zalophus californianus) is based on detection of elevated serum creatinine and blood urea nitrogen (BUN), urinalysis, renal ultrasound, and clinical signs.^1-7 Symmetric dimethylarginine (SDMA) is a renal-specific biomarker that correlates with serum creatinine and glomerular filtration rate in several species and appears to be an earlier and more accurate biomarker for kidney disease.^8-18 The objectives of this study were to validate the commercially available SDMA immunoassay and to assess the correlation of SDMA with creatinine in California sea lions. Forty banked serum samples from forty healthy sea lions and 73 banked serum samples from twelve sea lions with renal disease were submitted. General categories of histopathologic renal lesions included: inflammatory (9/12; 75%), dilation (3/12; 25%), necrosis/degeneration (4/12; 33%), mineralization (5/12; 41%), fibrosis (3/12; 25%), infection (2/12; 16%), and neoplasia (2/12; 16%). All analytical validation testing methods used were based on the best practices of IDEXX Laboratories Inc. as well as on the Clinical and Laboratory Standards Institute (CLSI) guidelines. Precision, analytical sensitivity, dynamic range, accuracy, analytical specificity, and sample stability were determined. Accuracy was assessed using 131 individual serum samples, containing both endogenous and spiked SDMA spanning the assay range were assayed using both the immunoassay and the gold standard liquid chromatography mass spectrometry methods, and compared using Passing-Bablok regression analysis. The correlation slope and intercept were 1.06 and 0.71, respectively. Precision of the assay was excellent. Both intra- and inter-assay precision were found to be less than 1.35 standard deviations from LOQ to 100 µg/dL. Dilutional linearity was demonstrated from 1 to 100 µg/dL. Interference from high levels of lipemia (≥482 mg/dL), bilirubin (≥58.7 mg/dL), or hemoglobin (≥574 mg/dL) was observed. SDMA concentrations were found to be stable after 2 and 7 days of storage at -20°C, 4°C, and 25°C. SDMA and serum creatinine measured from freeze-thawed stored samples show high correlation in individual sea lions (Kendall’s Tau=0.54; p<0.001). These data support that SDMA is a favorable renal biomarker in sea lions. Additional research is needed to establish a reference interval, and if this assay can be extended to other marine mammals.

Acknowledgements

The authors thank the veterinary and medical records office team, and training staff at the National Marine Mammal Foundation and U.S. Navy Marine Mammal Program for their excellent care of the U.S. Navy’s marine mammals.

*Presenting author

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