Assessment of cell cycle arrest biomarkers and neutrophil gelatinase-associated lipocalin to distinguish acute kidney injury from other diseases in dogs.

Abstract

BACKGROUND: Cell cycle arrest biomarkers (tissue inhibitor of metalloproteinase-2 [uTIMP-2] and insulin-like growth factor binding protein 7 [uIGFBP7]), and neutrophil gelatinase-associated lipocalin (NGAL) variables are valuable biomarkers for early diagnosis of acute kidney injury (AKI) in people. OBJECTIVES: To evaluate uTIMP-2, uIGFBP7, fractional excretion of NGAL (FeNGAL), and urinary to serum NGAL ratio (u/sNGAL) in healthy dogs, dogs with AKI, dogs with chronic kidney disease (CKD), and critically ill (CI) dogs. ANIMALS: Forty-two client-owned dogs (healthy, n&#x2009;=&#x2009;10; AKI, n&#x2009;=&#x2009;11; CKD, n&#x2009;=&#x2009;11; CI, n&#x2009;=&#x2009;10). METHODS: Prospective, observational study. After assessment of routine renal biomarkers, stress (uTIMP-2, uIGFBP7) and damage (NGAL) biomarkers were measured, using ELISA kits, and normalized to urinary creatinine (uCr). RESULTS: Normalized uTIMP-2 and [uTIMP-2]&#x2009;&#xd7;&#x2009;[uIGFBP7]/uCr were significantly higher in the AKI group (median 151.9 [range, 2.2-534.2] and 62.9 [1.1-266.8] pg/mL respectively), compared to healthy dogs (0.3 [0.2-74.7]; P&#x2009;<&#x2009;.001 and 0.16 [0.1-58.1] pg/mL; P&#x2009;<&#x2009;.001), dogs with CKD (0.7 [0.3-742.5]; P&#x2009;=&#x2009;.04 and 0.37 [0.2-180.1] pg/mL; P&#x2009;=&#x2009;.03) and CI dogs (1.9 [0.2-37.0]; P&#x2009;=&#x2009;.03 and 0.8 [0.1-16.1] pg/mL; P&#x2009;=&#x2009;.02). Fractional excretion of NGAL was significantly higher in dogs with AKI (54.17 [7.93-155.32] %), than in healthy (0.03 [0.01-0.21] %; P&#x2009;<&#x2009;.001) and CI dogs (3.05 [0.05-28.86] %; P&#x2009;=&#x2009;.02). CONCLUSIONS AND CLINICAL IMPORTANCE: Normalized uTIMP-2, [uTIMP-2]&#x2009;&#xd7;&#x2009;[uIGFBP7]/uCr, and FeNGAL can be valuable renal biomarkers for early diagnosis of AKI in dogs.