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. 2021 Sep 27;83(9):1465-1471.
doi: 10.1292/jvms.20-0698. Epub 2021 Sep 14.

Clinical evaluation of urinary liver-type fatty acid-binding protein for the diagnosis of renal diseases in dogs

Satoshi Takashima  1 , Yumiko Nagamori  1 , Keiichi Ohata  2   3 , Tsuyoshi Oikawa  2 , Takeshi Sugaya  3 , Yui Kobatake  1 , Naohito Nishii  1
Affiliations

Clinical evaluation of urinary liver-type fatty acid-binding protein for the diagnosis of renal diseases in dogs

Satoshi Takashima et al. J Vet Med Sci. .

Abstract

Liver-type fatty acid-binding protein (L-FABP) is a biomarker for the early detection of renal diseases in humans. L-FABP is a cytotoxic oxidation product secreted from the proximal tubules under ischemic and oxidative stress conditions. First, L-FABP gene expression in the kidney and liver was evaluated. Next, the urinary L-FABP concentrations in dogs with or without renal diseases were measured using a novel enzyme-linked immunosorbent assay kit. Urinary L-FABP was normalized relative to urinary creatinine (uCre) concentrations (µg/g uCre). Finally, the relationships between urinary L-FABP and renal biomarkers used in canine medicine or serum alanine transaminase (ALT) as an indicator of liver damage were examined. Serum and urine samples from 94 client-owned dogs including 23 dogs with renal diseases and 71 dogs without renal diseases were used for analysis. Relative L-FABP gene expression was confirmed both in the liver and kidney. Dogs with renal diseases had a significantly higher urinary L-FABP than those without, and its predictive cutoff value was 26 µg/g uCre. Urinary L-FABP was significantly correlated with serum creatinine (r=0.4674, P<0.01), urea nitrogen (r=0.4907, P<0.01), urine specific gravity (r=-0.5100, P<0.01), and urine protein/creatinine ratio (r=0.7216, P<0.01), but not with serum ALT. Hence, dogs with a high urinary L-FABP value were more likely to have renal diseases.

Keywords: dog; renal disease; urinary liver-type fatty acid-binding protein.

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Conflict of interest statement

Keiichi Ohata and Tsuyoshi Oikawa are the senior scientists of CMIC Holdongs Co., Ltd. (Tokyo, Japan), a company that produces ELISA kits with high sensitivity for L-FABP analysis. They were responsible for validation analyzes and measurement of an ELISA. No other potential conflicts of interest relevant to this article are reported.

Figures

Fig. 1.
Fig. 1.
Liver-type fatty acid-binding protein (L-FABP) mRNA transcription levels in the liver and kidney of normal dogs. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA was used as internal control. Data are normalized to GAPDH levels. The mean L-FABP mRNA was calculated from a standard curve. Error bars represent the S.D.
Fig. 2.
Fig. 2.
Urinary liver-type fatty acid-binding protein (L-FABP) in dogs with or without renal diseases. The triangle represents 24 dogs with renal diseases including chronic kidney disease (CKD, closed symbols, n=20) and acute kidney injury (AKI, open symbols, n=4). The circle represents 70 dogs without renal diseases including clinical healthy dogs (n=23), those with extrarenal urological disease (n=20), and those with non-urological diseases (n=27). The solid lines indicate median values (renal diseases: 238.3 µg/g uCre, clinically healthy: 1.9 µg/g uCre, extrarenal urological diseases: 4.0 µg/g uCre, and non- urological diseases: 3.2 µg/g uCre), and the dashed lines indicate the cutoff value for detecting renal diseases (26 µg/g uCre). *P<0.05 and **P<0.01.
Fig. 3.
Fig. 3.
Correlation between urinary liver-type fatty acid-binding protein (L-FABP) levels and serum creatinine (A), urea nitrogen (B), urine specific gravity (USG) (C), and urine protein/creatinine (UPC) ratio (D). The associations with urinary L-FABP were examined among serum creatinine, serum urea nitrogen and USG in 94 dogs. The relationship between urinary L-FABP and UPC ratio in 77 dogs without urinary sediment was examined.
Fig. 4.
Fig. 4.
Correlation between urinary liver-type fatty acid-binding protein (L-FABP) levels and serum alanine transaminase (ALT) levels in 94 dogs. There was no significant correlation between serum ALT and urinary L-FABP levels.
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