5.3.2. α-Glutathione S-Transferase (GST)

GST, a 28 kDa protein, is a cytosolic enzyme. The isoforms α and π (α-GST, π-GST) are typical of the human kidney [106]. α-GST is expressed in proximal tubular epithelial cells, and π-GST is expressed in distal tubular epithelial cells [45]. Both isoforms of GST are released from injured cells into the urine and were recently suggested to be promising biomarkers of kidney injury [107] in the context of cyclosporine-induced nephrotoxicity, cadmium exposure, administration of nephrotoxic antibiotics, acute transplant rejection [106], and critical illness in the ICU [106,108]. Recently, the utility of the α-GST and π-GST level in terms of predicting UUTO was explored. Children with UPJO exhibited significantly higher urinary α-GST excretion than controls. Urinary AUC-ROC values for UUTO detection were 0.90 for α-GST and 0.3 for π-GST. The predictive performance of α-GST was superior to that of urinary NGAL or KIM-1 [45].

5.3.3. Tissue inhibitor of metalloproteinases-2 (TIMP-2)/ insulin-like growth factor-binding protein 7 (IGFBP7)

TIMP-2 and IGFBP7 are new AKI biomarkers. In 2014, Food and Drug Administration approved TIMP-2/ IGFBP7 to be used in ICU patients to predict the risk of developing moderate to severe AKI [109]. TIMP-2 has a molecular weight of approximately 24 kDa and IGFBP7 has a molecular mass of 29 kDa [110]. Both of them are expressed and secreted by renal tubular cells, and involved in G1 cell cycle arrest during the early phases of cellular stress or injury caused by various insults (e.g., sepsis, ischemia, oxidative stress, and toxins) [111]. TIMP-2/ IGFBP7 shows the best accuracy among AKI biomarkers in patients with various types of AKI condition including AKI after kidney transplantation and AKI in critical care settings, sepsis and platinum-based chemotherapy, and chronic kidney damage induced by diabetes mellitus and congestive heart failure [112,113]. However, no study has yet evaluated the TIMP-2/ IGFBP7 as a biomarker of UUTO in an animal study or a clinical setting, and therefore it is urgently necessary.
