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Acute kidney injury (AKI) is a common complication in hospitalized patients and is associated with adverse short- and long-term outcomes. AKI is diagnosed by serum creatinine (SCr)-based consensus definitions that capture an abrupt decrease in glomerular filtration rate associated with AKI. However, SCr-based AKI definitions lack sensitivity and specificity for diagnosing structural kidney injury. Moreover, AKI is a heterogeneous condition consisting of distinct phenotypes based on its etiology, prognosis, and molecular pathways, and that may potentially require different therapies. SCr-based AKI definitions provide no information on these AKI phenotypes. This review highlights traditional and novel tools that overcome the limitations of SCr-based AKI definitions to improve AKI phenotyping., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The diagnosis of acute kidney injury (AKI), which is currently defined as an increase in serum creatinine (Scr) concentration, provides little information on the condition's actual cause. To improve phenotyping of AKI, many urinary biomarkers of tubular injury are being investigated. Because AKI cases are not frequently biopsied, the diagnostic accuracy of concentrations of Scr and urinary biomarkers for histologic acute tubular injury is unknown., Study Design: Cross-sectional analysis from multicenter prospective cohort., Settings & Participants: Hospitalized deceased kidney donors on whom kidney biopsies were performed at the time of organ procurement for histologic evaluation., Predictors: (1) AKI diagnosed by change in Scr concentration during donor hospitalization and (2) concentrations of urinary biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], liver-type fatty acid-binding protein [L-FABP], interleukin 18 [IL-18], and kidney injury molecule 1 [KIM-1]) measured at organ procurement., Outcome: Histologic acute tubular injury., Results: Of 581 donors, 98 (17%) had mild acute tubular injury and 57 (10%) had severe acute tubular injury. Overall, Scr-based AKI had poor diagnostic performance for identifying histologic acute tubular injury and 49% of donors with severe acute tubular injury did not have AKI. The area under the receiver operating characteristic curve (AUROC) of change in Scr concentration for diagnosing severe acute tubular injury was 0.58 (95% CI, 0.49-0.67) and for any acute tubular injury was 0.52 (95% CI, 0.45-0.58). Compared with Scr concentration, NGAL concentration demonstrated higher AUROC for diagnosing both severe acute tubular injury (0.67; 95% CI, 0.60-0.74; P=0.03) and any acute tubular injury (0.60; 95% CI, 0.55-0.66; P=0.005). In donors who did not have Scr-based AKI, NGAL concentrations were higher with increasing severities of acute tubular injury (subclinical AKI). However, compared with Scr concentration, AUROCs for acute tubular injury diagnosis were not significantly higher for urinary L-FABP, IL-18, or KIM-1., Limitations: The spectrum of AKI cause in deceased donors may be different from that of a general hospitalized population., Conclusions: Concentrations of Scr and kidney injury biomarkers (L-FABP, IL-18, and KIM-1) lack accuracy for diagnosing acute tubular injury in hospitalized deceased donors. Although urinary NGAL concentration had slightly higher discrimination for acute tubular injury than did Scr concentration, its overall AUROC was still modest., (Published by Elsevier Inc.)

There is a pressing need to find reliable biomarkers for the early diagnosis of silica-induced nephropathy. Abundant genes are upregulated in damaged kidneys with subsequent protein products appearing in the urine. Liver-type fatty acid-binding protein (L-FABP) and kidney injury molecule-1 (KIM-1) are among the most promising. Our objective was to study the importance of L-FABP and KIM-1 genes and their urinary proteins in the early detection of silica-induced renal injury, as compared with other conventional biomarkers. A cross-sectional study was conducted among 90 pottery workers occupationally exposed to silica, as compared to 90 controls. A full history taking and complete clinical examination were performed. Levels of serum creatinine, liver enzymes, urinary silicon, KIM-1, and L-FABP gene expression and protein products were measured. Estimated glomerular filtration rate (eGFR) was calculated, and abdominal ultrasound was performed. The results showed that the silica-exposed group had a statistically significant increase in serum creatinine and urinary silica, as well as a significant decrease in eGFR. Additionally, a significant increase in KIM-1 and L-FABP gene expression, associated with a significant increase in their urinary protein, was found among the exposed group. A positive correlation between urinary silica level and L-FABP gene expression was also found. A receiver operating characteristic curve analysis for L-FABP and KIM-1 gene as predictors for silica-induced nephropathy showed that L-FABP gene and protein specificity were greater than the KIM-1 gene and protein. Taken together, these findings suggest that the L-FABP gene and its protein product may be used as early indicators for renal injury among silica exposed workers. [ABSTRACT FROM AUTHOR]

Background: Congenital obstructive uropathy (OU) is a leading cause of pediatric kidney failure, representing a unique mechanism of injury, in part from renal tubular stretch and ischemia. Tubular injury biomarkers have potential to improve OU-specific risk stratification. Methods: Patients with OU were identified in the Chronic Kidney Disease in Children (CKiD) study. "Cases" were defined as individuals receiving any kidney replacement therapy (KRT), while "controls" were age- and time-on-study matched and KRT free at last study visit. Urine and plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), and liver-type fatty acid-binding protein (L-FABP) levels were measured at enrollment and annually and compared between cases and controls. Urine values were normalized to urine creatinine. Results: In total, 22 cases and 22 controls were identified, with median (interquartile range) ages of 10.5 (9.0–13.0) and 15.9 (13.9–16.9) years at baseline and outcome, respectively. At enrollment there were no differences noted between cases and controls for any urine (u) or plasma (p) biomarker measured. However, the mean pNGAL and uL-FABP/creatinine increased throughout the study period in cases (15.38 ng/ml per year and 0.20 ng/ml per mg/dl per year, respectively, p = 0.01 for both) but remained stable in controls. This remained constant after controlling for baseline glomerular filtration rate (GFR). Conclusions: In children with OU, pNGAL and uL-FABP levels increased over the 5 years preceding KRT; independent of baseline GFR. Future studies are necessary to identify optimal cutoff values and to determine if these markers outperform current clinical predictors. [ABSTRACT FROM AUTHOR]

Background: The study was designed to evaluate the applicability of combined assessment of urinary biomarkers and intra-renal Doppler flow indices for the prediction of contrast-induced acute kidney injury (CI-AKI) after coronary angiography/percutaneous coronary interventions (CA/PCI).Methods: This prospective observational study covered 95 consecutive patients with coronary artery disease subject to elective or urgent CA/PCI. Doppler intra-renal flow indices were assessed before and 1 h following CA/PCI. Urine samples were collected within 24 h before and 6 h after CA/PCI and assayed for urinary interleukin-18 (IL-18), liver-fatty acid-binding protein (L-FABP), and kidney injury molecule-1 (KIM-1) using ELISA method. CI-AKI was defined as ≥50% relative or ≥0.3 mg/dL absolute increase of serum creatinine concentration at 48 h post-procedurally.Results: CI-AKI was confirmed in nine patients (9.5%). CI-AKI onset was associated with significantly higher urinary KIM-1 at 6 h (P = 0.003) and ΔKIM-1 concentrations (P = 0.001), and urinary IL-18 at 6 h (P = 0.014) and ΔIL-18 concentrations (P = 0.012), however, L-FABP and ΔL-FABP levels were comparable in both groups. Receiver operating characteristic curve analysis denoted that post-procedural IL-18 levels at 6 h >89.8 pg/mg (AUC = 0.75, P = 0.007), KIM-1 at 6 h >0.425 ng/mg (AUC = 0.81, P = 0.001), renal resistive index (RRI) at 1 h >0.73 (AUC 0.88; P < 0.0001), and renal pulsatility index (RPI) at 1 h >0.86 (AUC = 0.86; P < 0.0001) predicted CI-AKI onset. Logistic regression analysis of postoperative predictors revealed that IL-18 and RRI were independent predictors of CI-AKI onset (AUC = 0.96; P < 0.0001).Conclusions: Joint assessment of early post-procedural urinary biomarkers and Doppler renovascular parameters aids early diagnosis of CI-AKI in patients undergoing coronary interventions. [ABSTRACT FROM AUTHOR]

Study Objective: To examine the change in liver-type fatty acid-binding protein (L-FABP) levels in patients undergoing aortic arch surgery and the correlation between L-FABP and postoperative acute kidney injury. Design: Prospective observational study. Setting: Operating room of a general hospital. Patients: 36 adult patients. Interventions and Measurements: Urine samples were obtained to measure urinary L-FABP at initiation of cardiopulmonary bypass (CPB) and 5 minutes after termination of hypothermic circulatory arrest. Main Results: 22 (61.1%) patients developed acute kidney injury within a 48-hour period. L-FABP increases more than a thousand-fold were found. In patients who subsequently developed acute kidney injury, significant increases in L-FABP were noted from 2.9 (3.6) ng/mg of creatinine before CPB to 62.1 (995.6) ng/mg of creatinine 5 minutes after termination of circulatory arrest. Values in patients who did not develop acute kidney injury increased from 1.1 (5.7) ng/mg before CPB to 1133.0 (6358.8) ng/mg of creatinine showing a significant mean difference (P = 0.011). The area under the L-FABP receiver operating characteristic curve at 5 minutes after termination of circulatory arrest was 0.758. A cutoff value of 75.13 ng/mg of creatinine yielded both good sensitivity (1.000) and specificity (0.546) for detecting non-acute kidney injury. Patients who developed acute kidney injury after aortic arch surgery demonstrated lower levels of urinary L-FABP. Conclusions: Low levels of urinary L-FABP may indicate kidney injury and lack of renal protection. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a common postoperative complication following cardiopulmonary bypass (CPB) surgery. New biomarkers to identify patients with early AKI (before increases in serum creatinine) are needed to facilitate appropriate treatment. This study aimed to test the role of urinary liver fatty-acid-binding protein (L-FABP) as an early biomarker for AKI in children undergoing CPB surgery. Methods: This is a case-control study of children undergoing CPB. AKI was defined as 50 % increase in serum creatinine at 48 h after surgery. For each patient, five serum and urine samples were obtained corresponding to time 0 h (presurgery) and 2, 6, 24, and 48 h after surgery. Results: Twenty-seven patients, median age 360 days, were enrolled. AKI developed in 11 patients (41 %); three needed renal replacement therapy (peritoneal dialysis); there were two deaths. There were significant differences between patients with and without AKI in L-FABP levels at 2, 6, and 48 h after surgery, length of hospital stay, and CPB time; there were no differences in gender, patient age, and body weight. L-FABP was normalized to urinary creatinine concentration at all time points, with area under the receiver operator curve (AUC ROC) 0.867 at 2 and 6 h postoperatively. Correlation coefficient between L-FABP and length of hospital stay after surgery was statistically significant ( r = 0.722, p value = 0.000). Conclusions: Our results suggest that urinary L-FABP can be used to diagnose AKI earlier than rise in serum creatinine in children undergoing CPB. [ABSTRACT FROM AUTHOR]

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Abstract: Background: To evaluate the value of basal urinary L-FABP (uL-FABP) excretion as a prognostic indicator of the progression of kidney function impairment in patients with chronic glomerulonephritis (CGN). Methods: One hundred twenty-three patients with newly diagnosed, biopsy-proven primary CGN were included. In all patients, and in 28 healthy subjects, uL-FABP was measured using an ELISA. Risk factors of the progression of kidney function were evaluated. The patients were in follow-up for at least 5years. Results: uL-FABP in the patients with CGN (76.58±17.3μg/g.cr) was greater than in the healthy subjects. A significant positive correlation between uL-FABP and proteinuria (R=0.501, P<0.01), serum creatinine (R=0.601, P<0.01) were found. Kaplan–Meier analysis revealed that uL-FABP >76.58μg/g.cr predicts progression of renal function. The cut off values for L-FABP at 119.8μg/g.cr was found to be more sensitive, area under the curve (AUC) was 0.95. Conclusion: Urinary L-FABP may be a useful clinical biomarker for monitoring chronic glomerular disease. Urinary L-FABP can help predict the progression of chronic glomerular disease. [Copyright &y& Elsevier]

Purpose: The value of NGAL (neutrophil gelatinase-associated lipocalin) and L-FABP (liver-type fatty acid binding protein) has been highlighted as a novel biomarker of detection of acute renal failure in children after cardiac surgery. Interventional cardiologists are being asked more frequently to perform percutaneous coronary intervention (PCI) and contrast nephropathy is its potentially serious complication. We aimed to prospectively assess NGAL and L-FABP in patients with normal scram creatinine undergoing PCI due to unstable angina. Material and Methods: We measured serum NGAL, urinary NGAL and L-FABP using commercially available kits before and after 2, 4, 12, 24 and 48 hours following PCI in 25 patients. Results: We found a significant rise in serum NGAL after 2 and 4 hours. Urinary NGAL and urinary L-FABP followed the same pattern. Both markers increased significantly after 4 hours and remained elevated up to 48 hours after PCI. Serum creatinine did not change significantly during the study period. Conclusions: NGAL and L-FABP may represent a sensitive early biomarkers of renal impairment after PCL Persistently increased urinary NGAL and L-FABP may suggest renotubular damage in this population. [ABSTRACT FROM AUTHOR]

Background: This study's aim is to measure liver-type fatty acid-binding protein (L-FABP) levels in urine using a rapid semiquantitative assay kit in the emergency department and to investigate whether the onset of acute kidney injury (AKI) after hospitalization can be predicted. Methods: This was a prospective observation study. Patients transferred to the emergency and critical care center were divided into two groups: urinary L-FABP negative and positive groups. The status and severity of AKI were evaluated for the respective patients based on the Kidney Disease: Improving Global Outcome (KDIGO) classification. We compared the proportion of AKI patients in the two groups. Results: In the urine L-FABP-positive group, many patients had a significant onset of AKI (p < 0.001). After excluding patients who were diagnosed as AKI for creatinine level at admission, urinary L-FABP could predict the onset of AKI after admission (p < 0.001). Conclusion: By measuring urinary L-FABP concentration using a rapid semiquantitative assay kit, there is the possibility that the onset of AKI after admission can be predicted from immediately after a patient is transported by ambulance. [ABSTRACT FROM AUTHOR]