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

Abstract

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 = 10; AKI, n = 11; CKD, n = 11; CI, n = 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] × [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 < .001 and 0.16 [0.1‐58.1] pg/mL; P < .001), dogs with CKD (0.7 [0.3‐742.5]; P = .04 and 0.37 [0.2‐180.1] pg/mL; P = .03) and CI dogs (1.9 [0.2‐37.0]; P = .03 and 0.8 [0.1‐16.1] pg/mL; P = .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 < .001) and CI dogs (3.05 [0.05‐28.86] %; P = .02). Conclusions and Clinical Importance Normalized uTIMP‐2, [uTIMP‐2] × [uIGFBP7]/uCr, and FeNGAL can be valuable renal biomarkers for early diagnosis of AKI in dogs.

Keywords

• canine
• early diagnosis
• insulin‐like growth factor binding protein 7 (IGFBP7)
• renal disease
• symmetric dimethylarginine (SDMA)
• tissue inhibitor of metalloproteinase‐2 (TIMP‐2)