Biomarkers for the early detection of acute kidney injury

Center for Acute Care Nephrology, Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, Ohio 45229-3039, USA.
Current opinion in pediatrics (Impact Factor: 2.53). 04/2011; 23(2):194-200. DOI: 10.1097/MOP.0b013e328343f4dd
Source: PubMed


Acute kidney injury (AKI) is a common and serious condition, the diagnosis of which depends on serum creatinine, which is a delayed and unreliable indicator of AKI. Fortunately, understanding the early stress response of the kidney to acute injuries has revealed a number of potential biomarkers. The current status of the most promising of these novel AKI biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), and interleukin (IL)-18, is reviewed.
In particular, NGAL is emerging as an excellent biomarker in the urine and plasma, for the early prediction of AKI, for monitoring clinical trials in AKI, and for the prognosis of AKI in several common clinical scenarios. However, biomarker combinations may be required to improve our ability to predict AKI and its outcomes in a context-specific manner.
It is vital that additional large future studies demonstrate the association between biomarkers and hard clinical outcomes independent of serum creatinine concentrations and that randomization to a treatment for AKI based on high biomarker levels results in an improvement in clinical outcomes.

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    • "All patients with AKI were classified into three categories (risk, injury, failure) based upon the magnitude of change in estimated GFR or urine output (UOP) as follows: risk stage, GFR decreased by 25% and/or UOP < 0.5 mL/kg/h for 8 hours; injury stage, GFR decreased by 50% and/or UOP < 0.5 mL/kg/h after 16 hours; failure stage, GFR decreased by 75% or GFR < 35 mL/min/1.73 m 2 and/or UOP < 0.3 mL/ kg/h for 24 hours or anuria for 12 hours [14]. "
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    ABSTRACT: Acute kidney injury (AKI) is common in the pediatric intensive care unit (PICU). We aimed to describe the etiology, clinical features, and outcome of AKI in pediatric patients and to determine the predictors for initiation of renal replacement and mortality. A retrospective chart review was performed of the medical records for all patients who were admitted to the PICU at King Abdulaziz University Hospital between January 1 and December 31, 2011. The pediatric-modified RIFLE criteria were used to classify AKI. We included 102 children with AKI, aged 4 - 60 months. Oliguria (61.5%, p < 0.0001) and hypervolemic signs (38.5%, p = 0.03) were more common among patients with RIFLE class failure. They also had the highest mortality (53.9%, p = 0.01). Oliguric patients were ~ 23 times more likely than their non-oliguric counterparts to be initiated on renal replacement therapy (RRT) (RR = 23.38, 95% CI: 3.07 - 178.16). Diuretic infusion was also a strong predictor for RRT initiation (RR = 10.00, 95% CI: 2.77 - 36.12). Hypervolemic patients were twice more likely to die during hospitalization in both unadjusted and adjusted models (RR = 2.06, 95% CI: 1.09 - 3.90, and aRR = 2.45, 95% CI: 1.09 - 5.51, respectively). Mechanical ventilation and RRT initiation were associated with higher likelihood of death (ARR = 13.23, 95% CI: 1.90 - 92.04, and ARR = 2.20, 95% CI: 1.18 - 4.12, respectively). Patients with RIFLE class Failure were about thrice more likely than patients with RIFLE class Risk to die in both the unadjusted (RR = 2.76, 95% CI: 1.35 - 5.65), and adjusted models (ARR = 2.88, 95% CI: 1.38 - 6.04). Children with AKI had longer PICU stay (0.0003) and higher mortality (< 0.0001) than the non-AKI group. Severe AKI predicted high mortality in critically ill children.
    Clinical nephrology 12/2014; 82(12):379-86. DOI:10.5414/CN108348 · 1.13 Impact Factor
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    • "Neutrophil gelatinase-associated lipocalin (NG- AL), a 25-kDa small protein, is a member of the lipocalin family that is expressed at low levels in several human tissues and rapidly released from renal tubular cells after various injuring stimuli [6]. Serum and urinary NGAL are arguably the most promising emerging biomarkers for early detection of acute kidney injury [7]. "
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    ABSTRACT: Background: A revised classification of chronic kidney disease (CKD) was proposed by the Kidney Disease: Improving Global Outcomes (KDIGO) in 2012. Neutrophil gelatinase-associated lipocalin (NGAL) was considered as one of the most promising biomarkers in clinical nephrology. The aim of this study was to examine the level of NGAL in patients with different impairment of GFR based on the new classification, and to evaluate whether NGAL in serum or urine was associated with different risk categories in CKD patients. Methods: A cross-sectional study was performed in 240 patients with CKD. NGAL, serum cystatin C, β₂-macroglobulin (β₂-MG), urine α₁-macroglobulin (α₁-MG) and albuminuria were tested in patients with various degrees of renal impairment. Results: Good correlation was found between the NGAL and the cystatin C, β₂-MG and the α₁-MG (r > 0.7). The level of sNGAL in CKD stage 3b was more than that in CKD stage 3a (P = 0.025). The concentration of the NGAL increased progressively with the increasing of risk categories (proposed by the revised CKD classification). The cutoff value of NGAL was calculated from stage 2 to stage 5. ROC analysis showed good AUC (sNGAL > 0.8, uNGAL > 0.7) and high specificity (sNGAL > 87%, uNGAL > 90%) on the cutoff value of NGAL. Conclusion: The results confirm NGAL as a useful biomarker in clinical nephrology which is helpful to diagnosis and evaluate the categories for CKD proposed by the KDIGO.
    International journal of clinical and experimental pathology 11/2014; 7(10):7172-81. · 1.89 Impact Factor
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    • "New potential candidate biomarkers for AKI include: NGAL, KIM-1, IL-18, and L-FABP (1, 12). "
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    ABSTRACT: Acute kidney injury (AKI) is closely associated with the mortality of hospitalized patients and long-term development of chronic kidney disease, especially in children. The purpose of our study was to assess the evidence of contrast-induced AKI after cardiac catheterization in children with heart disease and evaluate the clinical usefulness of candidate biomarkers in AKI. A total of 26 children undergoing cardiac catheterization due to various heart diseases were selected and urine and blood samples were taken at 0 hr, 6 hr, 24 hr, and 48 hr after cardiac catheterization. Until 48 hr after cardiac catheterization, there was no significant increase in serum creatinine level in all patients. Unlike urine kidney injury molecule-1, IL-18 and neutrophil gelatinase-associated lipocalin, urine liver-type fatty acid-binding protein (L-FABP) level showed biphasic pattern and the significant difference in the levels of urine L-FABP between 24 and 48 hr. We suggest that urine L-FABP can be one of the useful biomarkers to detect subclinical AKI developed by the contrast before cardiac surgery. Graphical Abstract
    Journal of Korean Medical Science 08/2014; 29(8):1102-7. DOI:10.3346/jkms.2014.29.8.1102 · 1.27 Impact Factor
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