NU01 - Evaluation of Three Urinary Biomarkers for the Detection of Meloxicam-induced Kidney Injury in Cats

Abstract:

Background: Urinary tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor binding protein-7 (IGFBP-7), and kidney injury molecule–1 (KIM-1) are tubular injury biomarkers used in human medicine. These urinary proteins are found in renal tubular cells and leak into the urine during acute kidney injury (AKI); in addition, KIM-1 is up-regulated during tubular injury. The utility of these urinary biomarkers in the prediction and diagnosis of feline AKI remains largely unknown.

Objectives: To establish the time course profile of urinary TIMP-2, IGFBP-7, and KIM-1 during repeated administrations of a nephrotoxic dose of meloxicam, and determine whether these profiles differ from saline-treated cats. Animals: Twelve healthy adult purpose-bred female cats.

Methods: Controlled experimental design. Cats were randomly allocated to control and treatment groups. Cats in the treatment group received meloxicam 0.3 mg/kg subcutaneously every 24 hours for 31 days. Cats in the control group received saline. Urinary TIMP-2, IGFBP-7, KIM-1, and creatinine were measured every 4 days. The concentration of urinary biomarkers between groups was compared by calculating the area under the curve (AUC) for each biomarker normalized for urinary creatinine.

Results: The AUCs for urinary IGFBP-7/UC and KIM-1/UC were higher in the treatment groups compared to the control groups. An increase in urinary TIMP-2/UC was detected in only 50% of the treatment group. Conclusions and Clinical Importance: Urinary IGFBP-7, KIM-1, and TIMP-2 may be reliable markers of renal tubular injury and diagnosing and monitoring feline AKI.