Table 3.

Comparative description of three novel urinary biomarkers and their utility in aminoglycoside-induced nephrotoxicity

Biomarker	Description	Utility in aminoglycoside-induced nephrotoxicity	Comments
Kidney Injury Molecule-1 (KIM-1)	Cell membrane glycoprotein upregulated by proximal tubule epithelial cells in response to toxicity [73] Confers a phagocytic phenotype [74]	Outperforms, with respect to sensitivity and specificity, traditional and novel biomarkers of AKI (serum creatinine, blood urea nitrogen, and NAG), as confirmed by histopathology in animal models [46] Early diagnostic marker for AKI and predictor of mortality risk [75] Elevated during aminoglycoside exposure in preterm neonates [47] and children with CF [49, 50]	Specific to proximal tubule Outperforms other biomarkers in pre-clinical models of aminoglycoside-induced nephrotoxicity
Neutrophil Gelatinase-associated Lipocalin (NGAL)	25-kDa protein expressed by kidney epithelial cells (and other tissues, as well as neutrophils) [76]	Upregulated in response to nephrotoxins in mouse models [77] Sensitive early predictor for AKI [75] Elevated during aminoglycoside exposure in preterm neonates [47]	Levels elevated in sepsis/inflammation [78] which may limit specificity
N-acetyl-β-D-glucosaminidase (NAG)	130- to 140-kDa lysosomal enzyme specific to proximal tubule epithelial cells [79]	Widely used in pre-clinical and clinical studies of aminoglycoside-induced nephrotoxicity [80] Elevated during aminoglycoside exposure in preterm neonates [47]	Outperformed by KIM-1 in pre-clinical models of aminoglycoside-induced nephrotoxicity

AKI, Acute kidney injury; CF, cystic fibrosis