Table 2 Acute kidney injury biomarkers in human studies
From: Clinical review: Biomarkers of acute kidney injury: where are we now?
AKI biomarker | Production/origin | Handling by the kidney | Sample sources | Detection time after renal injury | Confounding factors |
|---|---|---|---|---|---|
Neutrophil gelatinase associated lipocalin (NGAL; also known as oncogene 24p3) | 25 kDa glycoprotein produced by epithelial tissues throughout the body | Plasma NGAL is excreted via glomerular filtration and undergoes complete reabsorption in healthy tubular cells. It is also produced in distal tubular segments | Plasma and urine | 2-4 hours after AKI | Sepsis Malignancy Chronic kidney disease Pancreatitis COPD Endometrial hyperplasia |
Cystatin C | 13 kDa cysteine protease inhibitor produced by all nucleated human cells and released into plasma at constant rate independent of gender, race, muscle mass and hydration level | Freely filtered in glomeruli and completely reabsorbed and catabolised by proximal tubular cells; no tubular secretion (not detectable in urine in healthy subjects) | Plasma and urine (plasma cystatin C may be a marker of GFR; cystatin C only detectable in urine after tubular injury) | 12-24 hours post-renal injury | Systemic inflammation Malignancy Thyroid disorders Glucocorticoid deficiency and excess Smoking |
IL-18 | 18 kDa proinflammatory cytokine | Released from proximal tubular cells following injury | Plasma and urine | 6-24 hours after renal injury | Inflammation Sepsis Heart failure |
Kidney injury molecule-1 (KIM-1) | Transmembrane glycoprotein produced by proximal tubular cells after ischaemic or nephrotoxic injury; no systemic source | Present in urine after ischaemic or nephrotoxic damage of proximal tubular cells | Urine | 12-24 hours after renal injury | Renal cell carcinoma Chronic proteinuria Chronic kidney disease Sickle cell nephropathy |
Liver-type fatty acid-binding protein (L-FABP) | 14 kDa intracellular lipid chaperone produced in liver, intestine, pancreas, lung, nervous system, stomach and proximal tubular cells | Freely filtered in glomeruli and reabsorbed in proximal tubular cells; increased urinary excretion after tubular cell damage | Plasma and urine | 1 hour after ischaemic tubular injury | Chronic kidney disease Polycystic kidney disease Liver disease Sepsis |
N-acetyl-β-D-glucosaminidase (NAG) | >130 kDa lysosomal enzyme; produced in many cells, including proximal and distal tubular cells | Too large to undergo glomerular filtration; urinary elevations imply tubular origin | Plasma and urine | 12 hours | Diabetic nephropathy |
Retinol binding protein (RBP) | 21 kDa single-chain glycoprotein; specific carrier for retinol in the blood (delivers retinol from the liver to peripheral tissues) | Totally filtered by the glomeruli and reabsorbed but not secreted by proximal tubules; minor decrease in tubular function leads to excretion of RBP in urine | Plasma and urine | <12 hours | Type II diabetes Obesity Acute critical illness |
α-Glutathione S-transferase (αGST) | 47 to 51 kDa cytoplasmic enzyme produced in proximal tubule | Limited glomerular filtration; increased urinary levels following tubular injury | Urine | 12 hours |  |
α-Glutathione S-transferase (αGST) | 47 to 51 kDa cytoplasmic enzyme produced in distal tubules | Limited glomerular filtration; increased urinary levels following tubular injury | Urine | 12 hours |  |
Alanine aminopeptidase (AAP) | Enzymes located on the brush border villi of the proximal tubular cells | Released into urine after tubular injury | Urine | ? | Â |
Alkaline phosphatase (ALP) | Â | Â | Â | Â | Â |
γ-Glutamyl transpeptidase (γ-GT) |  |  |  |  |  |
Hepcidin | 2.78 kDa peptide hormone predominantly produced in hepatocytes; some production in kidney, heart and brain | Freely filtered with significant tubular uptake and catabolism (fractional excretion 2%) | Plasma and urine | ? | Systemic inflammation |
Hepatocyte growth factor (HGF) | Marker linked to renal tubular epithelial cell regeneration | Â | Â | Â | Â |
Netrin | Laminin-related molecule, minimally expressed in proximal tubular epithelial cells of normal kidneys | Highly expressed in injured proximal tubules | Urine | ? | Â |
Monocyte chemoattractant peptide-1 (MCP-1) | Peptide expressed in renal mesangial cells and podocytes | Detectable in urine | Urine | ? | Variety of primary renal diseases |
Calprotectin | Calcium-binding complex of two proteins of the S100 group (S100A8/S100A9); derived from neutrophils and monocytes; acts as activator of the innate immune system | Measure of local inflammatory activity; detectable in urine in intrinsic AKI | Urine | ? | Inflammatory bowel disease Urinary tract infection Probably CKD |