From the Guidelines
The most recommended biomarker for acute tubular injury (ATI) is neutrophil gelatinase-associated lipocalin (NGAL), which can be measured in urine and has been shown to perform better than serum NGAL when measured 2 days following a fluid challenge 1.
Key Biomarkers for ATI
Other biomarkers that have been used to evaluate ATI include:
- a1-microglobulin
- b2-microglobulin
- retinol binding protein These biomarkers can help identify renal tubular cell damage and distinguish ATI from other causes of acute kidney injury.
Clinical Implementation
NGAL is a valuable biomarker for early detection of ATI, and its level can predict 90-day mortality, with a cutoff value of 220–244 mg/g of creatinine reported as best for differentiating ATN from prerenal azotemia or HRS 1.
Comparison with Other Biomarkers
While other biomarkers such as kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), liver-type fatty acid binding protein (L-FABP), and tissue inhibitor of metalloproteinases-2 (TIMP-2) multiplied by insulin-like growth factor binding protein 7 (IGFBP7) have been studied, NGAL is the most studied biomarker for ATI, and its urinary measurement is preferred for its specificity to kidney damage 1.
Limitations and Future Directions
It is essential to note that NGAL measurements are not widely available in the United States for clinical use, highlighting the need for further research and development of biomarkers for ATI.
Clinical Decision-Making
In clinical practice, the use of biomarkers such as NGAL can help improve the diagnostic accuracy of AKI, recognize different pathophysiological processes, and assess AKI severity, ultimately leading to better patient outcomes 1.
From the Research
Acute Tubular Injury Biomarkers
- Neutrophil gelatinase-associated lipocalin (NGAL) is a recommended biomarker for acute tubular injury (ATI) 2, 3, 4, 5, 6
- NGAL is a member of the lipocalin family of proteins, produced and secreted by kidney tubule cells at low levels, but increases dramatically after ischemic, septic, or nephrotoxic injury of the kidneys 2
- Urinary NGAL can be used as a reliable predictor of early AKI in multi-trauma patients 3
- A cut-off point >25 ng/mL for NGAL has a sensitivity of 0.91 and specificity of 0.95 in predicting AKI 3
- NGAL can also be used for differential diagnosis between acute tubular necrosis (ATN) and other types of AKI in cirrhosis 5
- Other biomarkers such as cystatin C, kidney injury molecule-1 (KIM-1), klotho, and fibroblast growth factor-23 (FGF-23) can also predict AKI earlier and allow immediate interventions 6
Biomarker Levels and Prediction
- Urinary NGAL levels at admission were significantly higher among patients who subsequently developed AKI 3
- Serum cystatin C, KIM-1, NGAL, and FGF-23 levels were significantly elevated at admission in septic AKI patients 6
- The areas under the receiver operating curves demonstrated that serum cystatin C had modest discriminative powers for predicting AKI after sepsis 6
- NGAL was an independent predictive factor of AKI progression and 28-day mortality in cirrhosis patients 5
Clinical Applications
- NGAL can be used in clinical practice within the context of a diagnostic algorithm for differential diagnosis of AKI and outcome prediction in cirrhosis 5
- Cystatin C solely and combined with serum creatinine may accurately and sensitively predict septic AKI of patients on admission 6
- A multidisciplinary group of experts should come together to make recommendations and propose a consensus of clinical procedures to advance the most efficacious NGAL monitoring protocol for early detection and treatment of patients with AKI 2