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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    • "These effects were counteracted by recAP treatment. Half-life was determined reliably by transcutaneous measurement, allowing renal function to be determined in freely moving, awake, animals sequentially, and is therefore superior to currently used methods like creatinine clearance (Schock-Kusch et al., 2009; Devarajan, 2011; Schock-Kusch et al., 2011). In the complex pathogenesis of sepsis-associated AKI, the interaction between LPS and TLR4, specifically present on PTEC, induces a local inflammatory response within the kidney, which leads the development of AKI (Good et al., 2009). "
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    ABSTRACT: Background and Purpose Recently, two phase-II trials demonstrated improved renal function in critically ill patients with sepsis-associated acute kidney injury treated with the enzyme alkaline phosphatase. Here, we elucidated the dual active effect on renal protection of alkaline phosphatase. Experimental Approach The effect of human recombinant alkaline phosphatase (recAP) on LPS-induced renal injury was studied in Sprague-Dawley rats. Renal function was assessed by transcutaneous measurement of FITC-sinistrin elimination in freely moving, awake rats. The mechanism of action of recAP was further investigated in vitro using conditionally immortalized human proximal tubular epithelial cells (ciPTEC). Key Results In vivo, LPS administration significantly prolonged FITC-sinistrin half-life and increased fractional urea excretion, which was prevented by recAP co-administration. Moreover, recAP prevented LPS-induced increase in proximal tubule injury marker, kidney injury molecule-1 expression and excretion. In vitro, LPS-induced production of TNF-α, IL-6 and IL-8 was significantly attenuated by recAP. This effect was linked to dephosphorylation, as enzymatically inactive recAP had no effect on LPS-induced cytokine production. RecAP-mediated protection resulted in increased adenosine levels through dephosphorylation of LPS-induced extracellular ADP and ATP. Also, recAP attenuated LPS-induced increased expression of adenosine A2A receptor. However, the A2A receptor antagonist ZM-241385 did not diminish the effects of recAP. Conclusions and Implications These results indicate that the ability of recAP to reduce renal inflammation may account for the beneficial effect observed in septic acute kidney injury patients, and that dephosphorylation of ATP and LPS are responsible for this protective effect.
    British Journal of Pharmacology 07/2015; 172(20). DOI:10.1111/bph.13261 · 4.84 Impact Factor
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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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