Characterization of Kidney Injury Molecule‐1 in Cats

BACKGROUND Kidney disease (KD) is common in older cats and presumed to arise from subclinical kidney injuries throughout life. Sensitive markers for detecting kidney injury are lacking. Kidney injury molecule 1 (KIM-1) is a useful biomarker of kidney injury in humans and rodents. HYPOTHESIS/OBJECTIVES Feline KIM-1 is conserved across species, expressed in kidney, and shed into urine of cats with acute kidney injury (AKI). The objectives were to characterize the feline KIM-1 gene and protein, assess available immunoassays for detecting KIM-1 in urine of cats, and identify KIM-1 expression in kidney sections. ANIMALS Samples from 36 hospitalized and 7 clinically healthy cats were evaluated. Hospitalized cats were divided into 2 groups based on absence (n = 20) or presence (n = 16) of historical KD. METHODS Feline KIM-1 genomic and complementary DNA sequences were amplified, sequenced and analyzed to determine the presence of isoforms, exon-intron organization and similarity with orthologous sequences. Presence in urine was evaluated by immunoassay and expression in kidney by immunohistochemistry. RESULTS Three expressed feline KIM-1 transcript variants comprising 894, 810, and 705 bp were identified in renal tissue. KIM-1 immunoassays yielded positive results in urine of cats with conditions associated with AKI, but not chronic KD. Immunohistochemistry of kidney sections identified KIM-1 in proximal tubular cells of cats with positive urine immunoassay results. CONCLUSIONS AND CLINICAL IMPORTANCE Kidney injury molecule 1 was expressed in specific segments of the nephron and detected in urine of cats at risk of AKI. Urine KIM-1 immunoassay may be a useful indicator of tubular injury.