The evaluation of various biomarkers of acute kidney injury in cats using a toxin-induced model

Matthew Wun

Several feline-specific models, such as ischemia-reperfusion injury (IRI), remnant kidney (RK), and toxin-induced injury (TI), have been developed to study feline kidney disease. Each model has distinct advantages and limitations, making the careful selection of appropriate models critical for progressing research in feline nephrology. Using a toxin-induced model employing meloxicam, we aimed to compare serum concentrations of symmetric dimethylarginine (SDMA) and creatinine and evaluate the concentration vs time course profiles of urinary tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor binding protein-7 (IGFBP-7), and kidney injury molecule–1 (KIM-1) in cats before, during, and after induction of renal injury. Twelve healthy adult cats were obtained from a commercial breeder. Cats were randomly allocated to control and treatment groups. Cats in the treatment group received meloxicam 0.3 mg/kg subcutaneously (SC) every 24 hours for 31 days. Cats in the control group received saline (0.1 mL SC). Renal injury was defined as the presence of tubular damage, basement membrane damage, and/or interstitial inflammation in histological sections of kidney tissue. Serum creatinine and SDMA and urinary TIMP-2, IGFBP-7, KIM-1, and creatinine concentrations were measured every 4-6 days. In the control group, no cats developed renal azotemia. In the treatment group, four out of six cats developed elevated serum creatinine and histopathological evidence of renal injury. Three of these cats developed an elevation in serum SDMA. The time to the development of renal azotemia using serum creatinine or SDMA was not significantly different (p>0.05). The urinary biomarker concentrations between control cats and the four treatment group cats that developed elevated serum creatinine and histopathological evidence of renal injury were compared by calculating the area under the curve (AUC) for each biomarker normalized for urine creatinine (UC) concentration vs time course profile, and reported as mean ±SE. The AUC for urinary IGFBP-7/UC was higher (p = 0.0152) in the treatment group (0.042 ±0.0062) compared to the control group (0.02676 ±0.0018). The AUC for urinary KIM-1/UC was higher (p = 0.0083) in the treatment group (0.034 ±0.0055) compared to the control group (0.019 ±0.0022). An increase in urinary TIMP-2 was detected in only 50% of the treatment group. In this small pilot study, there was no evidence that serum SDMA was superior to serum creatinine at detecting impaired renal function, and urinary IGFBP-7 and KIM-1 increased in cats that developed AKI after repeated meloxicam administration.

The evaluation of various biomarkers of acute kidney injury in cats using a toxin-induced model

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