Table 2.

Biomarkers for S-AKI

Biomarker	Sample Source	Primary tubular release location	Physiologic Function	Use in S-AKI
NGAL	Plasma/Urine	Thick ascending limb and collecting duct	Anti-inflammatory and antiapoptotic protein that is involved in the synthesis and transport of iron into the renal tubular epithelium. 21,125,126 NGAL confers a bacteriostatic effect limiting bacterial iron uptake. 126	Urine NGAL is more specific than plasma NGAL.87,127 However, plasma NGAL has been shown to predict S-AKI recovery.128
KIM-1	Plasma/Urine	Proximal tubules	Type 1 transmembrane glycoprotein that has an anti-inflammatory effect on the kidney. Participates in renal recovery and tubular regeneration 21	In one prospective study, KIM-1 in the first 24h after admission had an AUC of 0.91 for the diagnosis of S-AKI. Non survivors had higher level of urinary KIM-1 at 24 and 48 hours than survivors.91
L-FABP	Urine	Proximal tubules	From the lipocalin family, involved in binding and transportation of longchain fatty acids to the peroxisome and mitochondria to be metabolized. Plays a role as antioxidant reducing cellular oxidative stress due to the binding of fatty acid oxidation products.92	In a cohort of 145 patients with S-AKI, urinary levels of L-FABP at admission were higher in non survivors with S-AKI and had a higher AUC score than APACHE II and SOFA score.93 It has also shown to be a predictor of mortality in septic children.129
TIMP 2-IGFBP7	Urine	Proximal tubules	Both proteins regulate cell growth and apoptosis. In the presence of cell injury, TIMP 2 and IGFBP7 are upregulated and may lead to G1 cell cycle arrest through the induction of p27 and p21, respectively.21,94,95	FDA approved biomarker for risk assessment tool of AKI in sepsis. Urine TIMP2/IGFBP7 has the highest specificity for renal injury, as there is minimal elevation in the presence of other organ injury.97 High TIMP2 and IGFBP7 levels in the early phase of septic shock are independent risk factors for progression to severe AKI in the next 24h.98