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. Author manuscript; available in PMC: 2009 Sep 11.
Published in final edited form as: Annu Rev Pharmacol Toxicol. 2008;48:463–493. doi: 10.1146/annurev.pharmtox.48.113006.094615

Table 2.

Biomarkers of acute kidney injury

Biomarker
 Comments
 Detection
 Species
Alanine aminopeptidase (AAP) 1. Proximal tubule brush border enzyme Colorimetry Rat, dog, human
 
 2. Instability may limit clinical utility
  
  
Alkaline phosphatase (AP) 1. Proximal tubule brush border enzyme. Human intestinal alkaline phosphatase is specific for proximal tubular S3 segment; human tissue nonspecific alkaline phosphatase is specific for S1 and S2 segments Colorimetry Rat, human
2. Levels may not correlate with extent of functional injury
 
 3. Instability may limit clinical utility
  
  
α-glutathione-S-transferase (α-GST) 1. Proximal tubule cytosolic enzyme ELISA Mouse, rat, human
2. Requires stabilization buffer for specimen storage and processing
 
 3. Upregulated in AKI and renal cell carcinoma
  
  
γ-glutamyl transpeptidase (γGT) 1. Proximal tubule brush border enzyme Colorimetry Rat, human
 
 2. Instability requires samples to be analyzed quickly after collection, limiting clinical utility
  
  
N-acetyl-β-glucosaminidase (NAG) 1. Proximal tubule lysosomal enzyme Colorimetry Mouse, rat, human
2. More stable than other urinary enzymes
3. Extensive preclinical and clinical data in a variety of conditions (nephrotoxicant exposure, cardiopulmonary bypass, delayed renal allograft function, etc.)
 
 4. Endogenous urea may inhibit activity
  
  
β2-microglobulin 1. Light chain of the MHC I molecule expressed on the cell surface of all nucleated cells ELISA, nephelometer Mouse, rat, human
2. Monomeric form is filtered by the glomerulus and reabsorbed by the proximal tubule cells
3. Early marker of tubular dysfunction in a variety of conditions
 
 4. Instability in acidic urine limits clinical utility
  
  
α1-microglobulin 1. Synthesized by the liver ELISA, nephelometer Mouse, rat, human
2. Filtered by the glomerulus and reabsorbed by proximal tubule cells
3. Early marker of tubular dysfunction; high levels may predict poorer outcome
 
 4. Stable across physiologic urinary pH
  
  
Retinol-binding protein (RBP) 1. Synthesized by liver, involved in vitamin A transport ELISA, nephelometer Mouse, rat, human
2. Filtered by glomerulus and reabsorbed by proximal tubule cells
3. Early marker of tubular dysfunction
 
 4. Increased stability in acidic urine when compared to β2-microglobulin
  
  
Cystatin C 1. Important extracellular inhibitor of cysteine proteases ELISA, nephelometer Mouse, rat, human
2. Filtered by the glomerulus and reabsorbed by proximal tubule cells
 
 3. Elevated urinary levels reflect tubular dysfunction; high levels may predict poorer outcome
  
  
Microalbumin 1. Established marker for monitoring progression of diabetic kidney disease ELISA Immunoturbidimetry Mouse, rat, dog, monkey, human
2. Elevated urinary levels may be indicative of proximal tubular damage
 
 3. Lack of specificity for AKI may limit its utility
  
  
Kidney injury molecule-1 (KIM-1) 1. Type-1 cell membrane glycoprotein upregulated in dedifferentiated proximal tubule epithelial cells ELISA, Luminex®-based assay Zebrafish, mouse, rat, dog, monkey, human
2. Ectodomain is shed and can be quantitated in urine following acute kidney injury in preclinical and clinical studies
3. Elevated urinary levels are highly sensitive and specific for AKI
 
 4. Upregulated following various models of preclinical and clinical AKI, fibrosis, renal cell carcinoma, and polycystic kidney disease
  
  
Clusterin 1. Expressed on dedifferentiated tubular epithelial cells ELISA Mouse, rat, dog, monkey, human
2. Elevated kidney and urinary levels are very sensitive for AKI in preclinical models
3. Upregulated in various rodent models of AKI, fibrosis, renal cell carcinoma, and polycystic kidney disease
 
 4. No clinical study demonstrating its use
  
  
Neutrophil gelatinase associated lipocalin (NGAL) 1. Initially identified bound to gelatinase in specific granules of the neutrophils but also may be induced in epithelial cells in the setting of inflammation or malignancy ELISA Luminex®-based assay Mouse, rat, human
2. Expression upregulated in kidney proximal tubule cells and urine following ischemic or cisplatin induced renal injury
3. Found to be an early indicator of AKI following cardiopulmonary bypass
 
 4. Specificity for AKI in setting of sepsis; pyuria needs to be further established
  
  
Interleukin-18 (IL-18) 1. Cytokine with broad immunomodulatory properties, particularly in setting of ischemic injury ELISA Luminex®-based assay Mouse, rat, human
2. Constitutively expressed in distal tubules; strong immunore-activity in proximal tubules with transplant rejection
 
 3. Elevated urinary levels found to be early marker of AKI and independent predictor of mortality in critically ill patients
  
  
Cysteine-rich protein (CYR-61) 1. Induced in proximal straight tubules of kidney and secreted in the urine within 3−6 h following ischemic kidney injury Western blot Mouse, rat, human
2. Urinary levels decrease rapidly in spite of progression of injury indicating stability issue
3. No clinical study demonstrating its use
 
 4. No quantitative method established
  
  
Osteopontin (OPN) 1. Upregulated in various rodent models of AKI ELISA Mouse, rat, monkey, human
2. The induction correlates with inflammation and tubulointerstitial fibrosis
 
 3. No clinical study demonstrating its use
  
  
Fatty acid binding protein (FABP) 1. Expressed in proximal tubule epithelial cells ELISA Mouse, rat, human
2. Current evidence suggests clinical utility as a biomarker in CKD and diabetic nephropathy
 
 3. Additional studies necessary to determine utility in setting of preclinical and clinical AKI
  
  
Sodium/hydrogen exchanger isoform (NHE3) 1. Most abundant sodium transporter in the renal tubule Immunoblotting Mouse, rat, human
2. Urinary levels found to discriminate between prerenal azotemia and AKI in ICU patients
 
 3. Samples require considerable processing, limiting assay throughput
  
  
Exosomal fetuin-A 1. Acute phase protein synthesized in the liver and secreted into the circulation Immunoblotting Rat, human
2. Levels in proximal tubule cell cytoplasm correspond to degree of injury
3. Urinary levels found to be much higher in ICU patients with AKI compared to ICU patients without AKI and healthy volunteers
4. Samples require considerable processing, limiting assay throughput
5. Additional studies necessary to determine utility in setting of preclinical and clinical AKI