Table 1.

Overview of origin, physiological function in the kidney, animal models, disadvantages and key clinical studies in different settings of biomarkers of acute kidney injury (AKI)

	NGAL	KIM-1	L-FABP	IL-18	IGFBP7 and TIMP-2	Calprotectin
Origin	Thick ascending loop of Henle and the intercalated cells of the collecting duct (Schmidt-Ott et al. 2007, Paragas et al. 2014)	Proximal tubule cells (Han et al. 2002, Ichimura et al. 2008)	Proximal tubule cells (Yamamoto et al. 2007)	Collecting duct (Gauer et al. 2007)  Tubular epithelial cells (Franke et al. 2012)	Unknown	Collecting duct and in filtrating immune cells (Fujiu et al. 2011, Seibert et al. 2016)
Physiological function in the kidney	Bacteriostatic function in the innate immune system, iron delivery to mammalian cells (Goetz et al. 2002, Flo et al. 2004, Bao et al. 2010)	Tubular regeneration by mediating phagocytosis of apoptotic bodies (Ichimura et al. 2008)	Regulation of fatty acids uptake and the intracellular transport (Chmurzyńska 2006)	Proinflammatory effect (Cheung et al. 2005)	Unknown	Polarization of M2 macrophages, promotion of repair after injury (Dessing et al. 2015)
Animal models	Holo-NGAL protects kidney from damage in response to ischaemia reperfusion injury (Mori et al. 2005)	KIM-1 knockout protects against damage in response to ischaemia reperfusion injury (Ismail et al. 2015b)	Human-L-FABP transgenic mice have less damage after ischaemia and reperfusion (Yamamoto et al. 2007)	IL-18-deficient mice are protected from ischaemia reperfusion-induced AKI (Wu et al. 2008)	Unknown	A lack of active calprotectin leads to more fibrosis after inn response to ischaemia reperfusion injury (Dessing et al. 2015)
Disadvantages	AKI-independent association with sepsis, CKD, UTI (Devarajan 2007, Schmidt-Ott 2011)	Is induced in various chronic proteinuric, inflammatory diseases (Smith et al. 2006)	Association of L-FABP with anaemia (Imai et al. 2015)	No reliable prediction of AKI	Unclear cellular sources and pathophysiology	Elevated in UTI (Heller et al. 2011)  Elevated in urothelial carcinoma (Ebbing et al. 2014)
Key clinical studies
Diagnosis of intrinsic AKI	AUC 0.87 (Singer et al. 2011)  AUC 0.81 (Nickolas et al. 2012)  AUC 0.95 (Nickolas et al. 2008)	AUC 0.71 (Nickolas et al. 2012)	AUC 0.70 (Nickolas et al. 2012)	AUC 0.64 (Nickolas et al. 2012)		AUC 0.97 (Heller et al. 2011)  AUC 0.99 (Seibert et al. 2013)  AUC 0.94 (Seibert et al. 2016)  AUC 0.94 (Chang et al. 2015)
Early prediction of AKI	AUC 0.67 (Parikh et al. 2011)  AUC 0.72 (Koyner et al. 2010)	AUC 0.69 (Koyner et al. 2010)  AUC 0.71 (Parikh et al. 2013)	AUC 0.66 (Parikh et al. 2013)  AUC 0.69 (Prowle et al. 2015)	AUC 0.75 (Parikh et al. 2013)  AUC 0.55 (Haase et al. 2008)	AUC 0.85 (Bihorac et al. 2014)  AUC 0.80 (Kashani et al. 2013)
Prediction of in-hospital death	Hall et al. (2011), Singer et al. (2011), Nickolas et al. (2012)	Hall et al. (2011), Gonzalez & Vincent (2012), Nickolas et al. (2012)	Doi et al. (2011), Nickolas et al. (2012)	Doi et al. (2011), Hall et al. (2011)
Prediction of long-term ESRD/mortality	Bolignano et al. (2009), Ralib et al. (2012), Coca et al. (2014)				Koyner et al. (2015b)