Renal expression and urinary excretion of liver‐type fatty acid‐binding protein in cats with renal disease

Abstract

Background Liver‐type fatty acid‐binding protein (L‐FABP) is a biomarker for early detection of renal disease in humans. Liver‐type fatty acid‐binding protein is cytotoxic oxidation products secreted from proximal tubules under ischemia and oxidative stress. Objective To examine renal expression and quantify urinary excretion of L‐FABP in catswith renal disease. Animals One hundred and thirty‐four client‐owned cats including 34 cats with serum creatinine (sCre) values >1.6 mg/dL and 10 other cats that died in clinics. Methods Tissue expressions of L‐FABP were examined by reverse transcription polymerase chain reaction and Western blotting. Urinary L‐FABP (uL‐FABP) and serum L‐FABP (sL‐FABP) levels were determined by enzyme‐linked immunosorbent assay. Anti‐liver‐type fatty acid‐binding protein antibody immunostained renal sections. Results Feline kidneys express L‐FABP. Strong L‐FABP signals were observed in the lumens of proximal tubular cells in 5 cats with high uL‐FABP excretion, but not in 5 cats with low uL‐FABP excretion. In 9 normal cats, uL‐FABP index was <1.2 μg/g urinary creatinine (uCre). High uL‐FABP indexes (>10.0 μg/g uCre) were detected in 7 of 100 cats with low sCre (<1.6 mg/dL) and 18 of 44 cats with high sCre (>1.6 mg/dL). There was a weak correlation between L‐FABP index and sCre, serum symmetric dimethylarginine (SDMA), or blood urea nitrogen (BUN), and these correlation coefficients were increased by analyzing only data of cats with sCre >1.6 mg/dL. There was a weak correlation between u L‐FABP index and sL‐FABP in all tested cats, but not in cats with high sCre. Conclusions and Clinical Importance This study demonstrates correlations between L‐FABP and current renal biomarkers for chronic kidney disease in cats, such as sCre and SDMA. Liver‐type fatty acid‐binding protein may be a potential biomarker to predict early pathophysiological events in feline kidneys.

Liver‐type fatty acid‐binding protein and neutrophil gelatinase‐associated lipocalin in cats with chronic kidney disease and hyperthyroidism

“…Hence, variations in uL‐FABP/Cr may be because of different severities of tubular damage and may indicate a variable CKD progression rate in cats. The significant correlation between uL‐FABP/Cr and sCr in this observation along with data in humans and CKD cats supports the hypothesis that uL‐FABP concentrations increase as kidney function declines 21,26 . Still, given the limited number of CKD cats in the present study, it is difficult to determine a relationship between the severity of azotemia and uL‐FABP/Cr values.…”

“…Similar to a recent study in cats with various kidney conditions, sL-FABP concentration and uL-FABP/Cr were significantly correlated in the group of CKD cats and healthy cats, suggesting the variables are co-dependent in cats. 26 This contrasts to the finding in patients with CKD where sL-FABP and uL-FABP concentrations are not correlated. 55 Since sL-FABP is produced mainly by the liver, these findings suggest that liver disease that may increase sL-FABP concentration should be ruled out when interpreting uL-FABP/Cr as a renal biomarker in cats.…”

“…The significant correlation between uL-FABP/Cr and sCr in this observation along with data in humans and CKD cats supports the hypothesis that uL-FABP concentrations increase as kidney function declines. 21,26 Still, given the limited number of CKD cats in the present study, it is difficult to determine a relationship between the severity of azotemia and uL-FABP/Cr values. A longitudinal study of uL-FABP in CKD cats including renal biopsy would allow the evaluation of its ability to monitor CKD progression.…”

“…21,24,55,57 Six (67%) of 9 CKD cats had measurable uL-FABP concentrations, corroborating a recent study reporting high uL-FABP/Cr values in 18/34 (53%) cats with azotemic CKD. 26 As tubulointerstitial inflammation is a predominant feature of CKD in cats, upregulated uL-FABP was expected. 58 Moreover, uL-FABP/Cr levels correlate with the degree of tubulointerstitial damage and predicted CKD progression in humans.…”

“…Urinary L‐FABP appears to be useful for detecting early‐stage renal disease and has prognostic value and utility in monitoring CKD progression in humans 20‐24 . Katayama et al suggest that urinary L‐FABP‐to‐creatinine ratio (uL‐FABP/Cr) may be a potential biomarker to predict early renal injury 25,26 . To corroborate these findings and to evaluate whether L‐FABP has potential as an early CKD biomarker in hyperthyroid cats, longitudinal study of L‐FABP in hyperthyroid cats along with comparison between hyperthyroid cats, healthy cats, and CKD cats are warranted.…”