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.
    Full-text · Article · Jul 2015 · British Journal of Pharmacology
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    • "Authors suggested that urinary IL-18 is nor useful as a CIN biomarker or that any effect is too small for it to be detected using this cohort size [38]. The influence of certain clinical situations on IL-18 concentration in urine, limiting its clinical usefulness in the diagnosis of AKI, was proved for immune disorders, nephrotoxic drugs such as cisplatin or endotoxemia [9]. The current opinion of CIN Consensus Working Panel indicates that potential AKI markers currently have limited clinical utility, but they are still an important research tool and may in future lead to redefinition of CI-AKI [20]. "
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    ABSTRACT: The aim of the study was to determine the usefulness of interleukin 18 (iL-18) and neutrophil-gelatinase associated lipocalin (ngaL) in the risk assessment of contrast nephropathy in children. the study included patients among whom radiological examinations were performed using intravascular contrast agent. the material consisted of 33 children (19 girls, 14 boys) aged 6.37 ±5.41 years. 20/33 (61%) of patients had hydronephrosis, 9/33 (27%) had other urinary tract defects referred as "no hydronephrosis" and 4/33 (12%) had urolithiasis. NGal determination was performed with the use of human Lipocalin-2/ngaL immunoassay. to determine the concentration of human iL-18 an eLisa kit (MbL international Corporation) was used. there were no statistically significant differences in the concentrations of ngaL and iL-18 in serum determined before the procedure, and after the administration of contrast agent. Concentrations of ngaL and iL-18 were determined in urine three times: before the procedure, 2-4 hours after administration of the contrast agent, and 48 hours after the performed procedure. the analysis showed that the concentration of iL-18 and ngaL in urine did not differ significantly in three consecutive preformed measurements. the study has also found no statistically significant differences between serum creatinine before and 48 hours after injection of contrast. implementation of new biomarkers such as ngaL and iL-18 expands the possibilities of renal function assessment in children undergoing radiological procedures using contrast agents. in examined children with normal or slightly impaired renal function they did not demonstrate the risk of contrast nephropathy.
    Full-text · Article · Jan 2015
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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.
    Full-text · Article · Dec 2014 · Clinical nephrology
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