Table 2.
Review of biomarkers for acute kidney injury.
| Biomarker | Mechanism of release | Key trials |
|---|---|---|
| NGAL | Proximal and distal tubular epithelial cells in response to injury. Also systemically from other organs under stress (i.e., sepsis) | Haase et al. meta-analysis of 2358 patients: NGAL an AUC of 0.815 across all settings to detect AKI [14] |
| Cystatin C | Synthesized and released into plasma by all nucleated cells at a constant rate | Ahlström et al.’s ICU study with 202 patients found an AUC of 0.901 for early detection of AKI [60] |
| IL-18 | Cleaved to mature form in proximal tubular cells after ischemia–reperfusion injury but also general inflammatory states | Parikh et al. showed elevated levels in 52 patients with AKI versus 86 normal individuals [34] |
| KIM-1 | Upregulated in proximal tubular epithelial cells in response to injuries such as ischemia–reperfusion and nephrotoxins | Han et al. shows favorable AUC of 0.90 for the diagnosis of established AKI in 44 patients versus 30 controls [24] |
| BNP | Ventricular myocytes in response to hemodynamic stress | Breathing Not Properly trial of 1586 patients found that the diagnostic accuracy of BNP at 100 pg/ml was 83.4%, with a negative-predictive value of 96% at a cutoff of 50 pg/ml [62] |
| SDF-1 | Constitutively expressed by most organs but upregulated after injury or DNA damage | Togel et al. showed in mice that SDF-1 is a mediator for the migration of CXCR4 (its receptor)-expressing cells to the kidney with possible renoprotective effects as well as renal repair [41] |
| Urinary exosomes | All segments of the nephron as a part of normal signaling; upregulated in response to stress | Zhou et al. found exosomes containing ATF3 in four patients with AKI compared with eight controls [44] |
| Osteopontin | Loop of Henle and distal nephrons in normal kidneys; upregulated in all tubular and glomerular segments following kidney damage | Lorenzen et al. showed it osteopontin be a predictor of mortality with a AUC of 0.82, sensitivity of 100% and specificity of 61% for a cutoff value of 577 ng/ml in 109 critically ill patients [39] |
| NAG | Lysosomal enzyme leaked into renal tubules from damaged proximal tubular cells | Han et al. showed NAG had an AUC of 0.97 in distinguishing established AKI in 44 patients versus 30 controls [25] |
AKI: Acute kidney injury; ATF3: Activating transcription factor 3; AUC: Area under the curve; BNP: B-type natriuretic peptide; ICU: Intensive care unit; KIM-1: Kidney injury molecule-1; NAG: N-acetyl-β-D-glucosaminidase; NGAL: Neutrophil gelatinase-associated lipocalin; SDF-1: Stromal cell-derived factor-1.