Table 1.

Domains of kidney disease to be assessed

Domains of Kidney Disease to be Assessed	Serum Creatinine	Role of Biomarkers/Examples and Limitations
Renal reserve	Serum creatinine may not rise until >50% decrease in kidney functioning units or kidney mass.	Cut-offs for AKI biomarkers in patients with and without baseline CKD not established.
		Use of novel CKD biomarkers such as collagen PIIINP in conjunction with AKI biomarkers not yet established in assessing AKI on CKD.
Delay in diagnosis of reduced GFR	Delayed diagnosis by 48–72 h in settings of acute injury.	Earlier diagnosis at the time of insult.
		NGAL, KIM-1, IL-18, IGFBP7/TIMP-2 within 12 h postop or presentation with critical illness.
Phenotyping	Cannot distinguish between functional vs. structural kidney injury within etiologies of kidney disease.	Can distinguish between functional (prerenal) vs. structural kidney injury.
		Current biomarkers (i.e., NGAL, KIM-1) unable to subtype structural AKI in settings such as ischemic vs. septic.
Specificity (location of kidney injury)	Cannot distinguish between glomerular injury or tubular injury along the nephron.	Biomarkers can help localize injury within the kidney.
		Glomerular: Albumin
		Proximal tubule: NGAL, KIM-1, IL-18, Albumin
		Distal tubule: NGAL, L-FABP
Recovery	Estimations of kinetic GFR possible, currently not used clinically.	Decreasing levels of injury biomarkers may predict recovery.
		“Recovery” biomarker yet to be determined.
		Overall kinetics of biomarkers in initial injury and persistent injury vs. recovery not fully established.
		Differentiation of normal repair from maladaptive healing promoting fibrosis with repair biomarkers such as NGAL and YKL-40 needs to be established.

AKI, acute kidney injury; GFR, glomerular filtration rate; CKD, chronic kidney disease; NGAL, neutrophil gelatinase-associated lipocalin; KIM-1, kidney injury molecule-1; TIMP-2, tissue inhibitor of metalloproteinases-2; L-FABP, liver-type fatty acid-binding protein.