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Chitinase 3-like 1 (CH3L1) and liver fatty acid binding protein (L-FABP) are promising biomarkers for the early diagnosis of acute kidney injury (AKI). Here, a highly sensitive method for the quantitative detection of CH3L1 and L-FABP by surface-enhanced Raman spectroscopy (SERS) based on graphene oxide/gold and silver core-shell nanoparticles (GO/Au@Ag NPs) was proposed. The results showed that such GO/Au@Ag substrate can achieve rapid sensing of CH3L1 and L-FABP with a wide response range (2 × 10 -1 to 2 × 10 -8 mg/mL and 1.2 × 10 -1 to 1.2 × 10 -8 mg/mL, respectively) and high sensitivity. The detection limits of CH3L1 and L-FABP were 1.21 × 10 -8 mg/mL and 0.62 × 10 -8 mg/mL, respectively. In addition, the simultaneous detection of the two biomarkers in serum was demonstrated, showing the feasibility of this method in the complex biological environment. The detection of CH3L1 and L-FABP will greatly improve the early diagnosis and intervention of AKI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Delayed diagnosis of abdominal injuries and hemorrhagic shock leads to secondary complications and high late mortality in severely traumatized patients. The liver fatty acid-binding protein (L-FABP) is expressed in intestine, liver and kidney; the neutrophil gelatinase-associated lipocalin (NGAL) in colon and kidney. We hypothesized that l-FABP is an early biomarker for abdominal injury and hemorrhagic shock and that l-FABP and NGAL are specific markers for detection of liver and/or kidney injuries., Patients and Methods: Traumatized patients with an age ≥18 years and an abdominal injury (AIS abd ≥2), independently from Injury Severity Score (ISS), were prospectively included from 04/2018 to 05/2021. 68 patients had an abdominal injury ("Abd") and 10 patients had an abdominal injury with hemorrhagic shock ("HS Abd"). 41 patients without abdominal injury and hemorrhagic shock but with an ISS ≥ 25 ("noAbd") were included as control group. Four abdominal subgroups with isolated organ injuries were defined. Plasma l-FABP and NGAL levels were measured at admission (ER) and up to two days post-trauma., Results: All patient groups had a median ISS≥25. In ER, median l-FABP levels were significantly higher in "HS Abd" group (1209.2 ng/ml [IQR=575.2-1780.3]) compared to "noAbd" group (36.4 ng/ml [IQR=14.8-88.5]), and to "Abd" group (41.4 ng/ml [IQR=18.0-235.5]), p<0.001. In matched-pair-analysis l-FABP levels in the group "Abd" were significantly higher (108.3 ng/ml [IQR=31.4-540.9]) compared to "noAbd" (26.4 ng/ml [IQR=15.5-88.8]), p = 0.0016. l-FABP correlated significantly with clinical parameters of hemorrhagic shock; the optimal cut-off level of l-FABP for detection was 334.3 ng/ml (sensitivity: 90%, specificity: 78%). Median l-FABP-levels were significantly higher in patients with isolated liver or kidney injuries and correlated significantly with AST, ALT and creatinine value. Median NGAL levels in the ER were significantly higher in "HS Abd" group (115.9 ng/ml [IQR=90.6-163.8]) compared to "noAbd" group (58.5 ng/ml [IQR=41.0-89.6],p<0.001) and "Abd" group (70.5 ng/ml [IQR=53.3-115.5], p<0.05). The group "Abd" showed significant higher median NGAL levels compared to "noAbd", p = 0.019. NGAL levels correlated significantly with clinical parameters of hemorrhagic shock., Conclusion: L-FABP and NGAL are novel biomarkers for detection of abdominal trauma and hemorrhagic shock. l-FABP may be a useful and promising parameter in diagnosis of liver and kidney injuries, NGAL failed to achieve the same., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Ltd.)

Patients undergoing cardiac catheterization are at high risk of post-procedure acute kidney injury (AKI) and may experience persistent renal damage after an initial insult, a state known as acute kidney disease (AKD). However, the association between AKD and urinary renal biomarkers has not yet been evaluated in this population. We enrolled 94 patients who underwent elective cardiac catheterization to investigate patterns of urinary renal biomarkers and their associations with post-procedure AKD. Serial urinary renal biomarker levels were measured during pre-procedure, early post-procedure (12-24 h), and late post-procedure (7-10 days) periods. In our investigation, 42.55% of the enrolled patients developed AKD during the late post-procedure period. While the liver-type free-fatty-acid-binding protein level increased sharply during the early post-procedure period, it returned to baseline during the late post-procedure period. In contrast, interleukin-18 (IL-18) levels increased steadily during the post-procedure period. Early post-procedure ratios of IL-18 and gelsolin (GSN) were independently associated with subsequent AKD (odds ratio (95% confidence interval), 4.742 (1.523-14.759) for IL-18 ratio, p = 0.007; 1.812 (1.027-3.198) for GSN ratio, p = 0.040). In conclusion, post-procedure AKD is common and associated with early changes in urinary IL-18 and GSN in patients undergoing cardiac catheterization.

Background: Since heatstroke-induced acute kidney injury (AKI) can progress to chronic kidney disease, it would be useful to detect heatstroke-induced AKI and severe heat-related illness in the early phase. We studied the epidemiology of heat-related illness among patients in the Japanese Ground Self-Defense Force and evaluated the relationship between heat-related illness severity and early urinary biomarkers for AKI., Methods: We enrolled patients who were diagnosed with heat-related illness at the Self-Defense Force Fuji Hospital from 1 May to 30 September 2020. We compared the urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), liver fatty acid-binding protein (L-FABP), N-acetyl-β-D-glucosaminidase (NAG) and β2-microglobulin levels according to the severity of heat-related illness as defined by positive scores for the Japanese Association of Acute Medicine Heatstroke Working Group (JAAM-HS-WG) criteria (0, mild; 1, moderate; ≥2, severe)., Results: Of the 44 patients, kidney injury, defined as serum creatinine (sCr) ≥1.2 mg/dL, was seen in 9 (20.5%) patients. Urinary NAG, NGAL and L-FABP levels were significantly higher in the ≥2 JAAM-HS-WG criteria group than in the 0 group. Furthermore, urinary L-FABP levels were positively correlated with sCr levels. In contrast, the urinary KIM-1 levels showed the best correlation with serum cystatin C (sCysC) among these biomarkers., Conclusions: We conclude even mild to moderate heatstroke could lead to AKI. Urinary L-FABP is useful for detecting heatstroke-induced AKI and patients with severe heat-related illness requiring immediate treatment. Urinary KIM-1 may detect heatstroke-induced AKI in terms of sCysC, although it was not related to the severity of heat-related illness., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Liver-type fatty acid-binding protein (L-FABP) is a promising biomarker for the early prediction of acute kidney injury (AKI). However, the clinical utility of L-FABP in different populations or settings remains unclear. We present a meta-analysis of studies evaluating the performance of L-FABP in AKI prediction., Methods: We performed a literature search in MEDLINE, EMBASE, and Cochrane library, using search terms "acute kidney injury" and "L-FABP." Studies investigating the performance characteristics of L-FABP for the early diagnosis of AKI were included. Data about patient characteristics, diagnostic criteria of AKI, quantitative data required for construction of a 2 × 2 table (number of participants, sensitivity, specificity, and case number), study settings, and outcomes were extracted. The bivariable model was applied to calculate the estimated sensitivity and specificity of L-FABP. A summary ROC curve was created by plotting the true-positive rate against the false-positive rate at various cutoff values from different studies., Results: We found 27 studies reporting measurement of urine (n = 25 studies) or plasma (n = 2 studies) L-FABP. Overall, the estimated sensitivity was 0.74 (95% CI: 0.69-0.80) and specificity was 0.78 (95% CI: 0.71-0.83). L-FABP demonstrated a stable area under the ROC of 0.82 (95% CI: 0.79-0.85) in variable clinical settings including intensive care unit, surgery, and contrast-induced AKI. In subgroup analysis excluding pediatric and post radiocontrast exposure cohorts, L-FABP had comparative diagnostic performance with neutrophil gelatinase associated lipocalin (NGAL)., Conclusions: Despite broad prevalence, L-FABP is a clinically useful marker with moderate accuracy in variable clinical settings as demonstrated in our subgroup analysis. Except for pediatric patients and those post-radiocontrast exposure, L-FABP has comparable discriminative capability as NGAL., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Acute kidney injury (AKI) was a common clinical complication among critically ill patients in Intensive Care Unit with high morbidity and mortality. Human liver fatty acid-binding protein (L-FABP) as a renal tubular injury biomarker was considered a predictor of AKI; however, high-throughput and sensitive detection methods were still urgently needed. We constructed a sensitive and rapid detection method for detecting L-FABP and for exploring the clinical application of L-FABP as a predictor for AKI., Methods: We developed an automated detection method of chemiluminescent immunoassay to measure L-FABP and evaluated the analytical performance of the new methodology including analytical selectivity, analytical sensitivity, linear range, the minimum limit of detection (LOD), repeatability, and accuracy. One hundred patients were enrolled in this study to explore the predictive and diagnostic ability for AKI., Results: The chemiluminescent immune-based L-FABP assay had outstanding analytical sensitivity including the detection limit of 0.88 ng/ml, and a wide linear range of 2 ng/ml to 160 ng/ml. It also exhibited excellent repeatability with intra-analysis CVs of 8.73%, 4.72%, and 3.79%, respectively, and the inter-analysis CVs of 13.47%, 7.28%, and 5.94%, respectively. The recovery rate assay exhibited a good accuracy with three L-FABP concentration of 99.76%, 102.27%, and 96.92%, respectively. The reference interval of L-FABP was between 0.88 ng/ml and 5.98 ng/ml. The evaluation of predictive and diagnostic performance showed that higher concentration of L-FABP indicated higher risk of AKI occurrence and disease progression., Conclusions: The clinical application of rapid and sensitive detection method of L-FABP based on the newly developed chemiluminescent immunoassay could offer benefits for patients. L-FABP was a potentially predictive and diagnostic biomarker for AKI., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Severe acute respiratory syndrome Coronavirus 2 has rapidly spread worldwide, with acute kidney injury (AKI) as one of the manifestations with unknown causal mechanisms. We aimed to investigate tubular injury by assessing tubular markers and their association with the severity of Coronavirus disease 2019 (COVID-19)., Methods: We examined the associations between laboratory markers and urinary levels of N-acetyl-β-D-glucosaminidase (uNAG), β2-microglobulin (u β2MG), α1-microglobulin (u α1MG), and liver-type fatty acid binding protein (L-FABP). We studied 18 COVID-19 patients without previous chronic kidney disease and analyzed the relationship between the urinary biomarkers and inflammatory markers in patients with severe (n = 7) or non-severe (n = 11) COVID-19, defined by requirements of supplemental oxygen., Results: Fourteen patients (78%) showed abnormal urinalysis findings and two (11%) developed AKI. Patients with severe COVID-19 had significantly higher levels of proteinuria, uNAG, uβ2MG, uα 1MG, and L-FABP than those with non-severe disease. Serum levels of interleukin-6 (IL-6) were significantly higher on admission in all severe COVID-19 cases and correlated with the levels of L-FABP, uβ2MG, uα1MG, uNAG, and proteinuria. Moreover, the changes in serum IL-6 (ΔIL-6) levels from baseline to 7 days after admission significantly correlated with ΔL-FABP and Δuβ2MG., Conclusions: Levels of tubular injury markers, especially L-FABP and uβ2MG, were significantly associated with IL-6 levels even in patients with no evident AKI. This suggests that L-FABP and uβ2MG could be useful as early detective biomarkers for COVID-19 associated renal injury., (© 2021. Japanese Society of Nephrology.)

Background: Liver-type fatty acid-binding protein (L-FABP) and neutrophil gelatinase-associated lipocalin (NGAL) are candidate biomarkers for the detection of early chronic kidney disease (CKD) in cats., Objective: To evaluate urinary and serum L-FABP and NGAL concentrations in CKD cats and in hyperthyroid cats before and after radioiodine ( 131 I) treatment., Animals: Nine CKD cats, 45 healthy cats and hyperthyroid cats at 3 time points including before (T0, n = 49), 1 month (T1, n = 49), and 11 to 29 months after (T2, n = 26) 131 I treatment., Methods: Cross-sectional and longitudinal study. Serum L-FABP (sL-FABP), serum NGAL (sNGAL), urinary L-FABP (uL-FABP), and urinary NGAL (uNGAL) were compared between the 3 groups and between hyperthyroid cats before and after treatment. Data are reported as median (min-max)., Results: CKD cats had significantly higher sL-FABP (13.50 [3.40-75.60] ng/ml) and uL-FABP/Cr (4.90 [0.97-2139.44] µg/g) than healthy cats (4.25 [1.34-23.25] ng/ml; P = .01 and 0.46 [0.18-9.13] µg/g; P < .001, respectively). Hyperthyroid cats at T0 had significantly higher uL-FABP/Cr (0.94 [0.15-896.00] µg/g) than healthy cats (P < .001), thereafter uL-FABP/Cr significantly decreased at T2 (0.54 [0.10-76.41] µg/g, P = .002). For the detection of CKD, uL-FABP/Cr had 100% (95% confidence interval [CI], 66.4-100.0) sensitivity and 93.2% (95% CI, 81.3-98.6) specificity. There were no significant differences in sNGAL and uNGAL/Cr between the 3 groups., Conclusions and Clinical Importance: L-FABP, but not NGAL, is a potential biomarker for the detection of early CKD in cats. Utility of uL-FABP to predict azotemia after treatment in hyperthyroid cats remains unknown., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Acute kidney injury (AKI) is one of the most common and morbid complications of decompensated cirrhosis. Management of AKI is dictated by cause: prerenal AKI is treated with volume resuscitation; hepatorenal syndrome (HRS), with intravenous albumin and vasoconstrictors; and acute tubular necrosis, with supportive care. However, differentiating between causes is difficult using creatinine-based definitions of AKI alone. The use of novel kidney biomarkers in AKI and cirrhosis provides an opportunity to improve both the diagnosis and prognosis of this vulnerable population. This review examines the challenges of AKI in cirrhosis and the research experience around novel kidney biomarkers in cirrhosis. Specific focus is paid to the tubular injury marker neutrophil gelatinase-associated lipocalin (NGAL), which has been the most studied in liver disease and has demonstrated the strongest performance in differentiating the cause of AKI (acute tubular necrosis vs functional injury such as prerenal AKI or HRS), as well as improving the prognostic performance of mortality prediction models such as the model for end stage liver disease (MELD) score. We advocate for the discussion of incorporating markers such as NGAL in the next iteration of HRS guidelines and identify areas for future research in this clinical condition., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to assess the levels of selected markers in patients who underwent planned or emergency coronary angiography and to examine if they correlated with the occurrence of AKI., Methods: The study included 52 patients who underwent planned or emergency coronary angiography and received contrast agent. Serum levels of markers (NGAL, L-FABP, KIM-1, IL-18) were analyzed in all patients using ELISA tests, at baseline, after 24 and 72 h from angiography., Results: 9.62% of patients developed CI-AKI. No significant differences were observed between markers levels in patients who developed CI-AKI and those who did not. After 24 h, serum levels of IL-18 were higher in patients with CI-AKI, however, this difference was on the verge of significance. Increase in serum NGAL, KIM-1 and IL-18 was observed after 24 h. Serum levels of biomarkers were insignificantly higher in group with CI-AKI. Significant changes in levels in time (baseline vs. 24 h vs. 72 h) were observed only for NGAL [157.9 (92.4-221.0) vs. 201.8 (156.5-299.9) vs. 118.5 (73.4-198.7); p < 0.0001]. No significant correlations were observed between the decrease in eGFR or the increase in creatinine and biomarkers level., Conclusion: Obtained results do not allow for the indication of efficient AKI biomarkers. Their further validation in large studies of CI-AKI patients is required.

Objective: The aim of this study was to investigate the clinical course, selected biochemical parameters and concentrations of renal injury biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and liver-fatty acid binding protein (L-FABP) in patients with immunoglobulin A vasculitis (IgAV) to identify the markers associated with nephritis in the course of the disease (IgAVN)., Methods: The study involved 29 children with IgAV and 34 healthy controls. Eleven (38%) patients had renal involvement (IgAV-N) and 18 (62%) did not exhibit nephritis (IgAV-noN). Initial laboratory tests, determining the concentrations of NGAL, KIM-1 and L-FABP in serum and urine, were conducted on children from the study group in an acute phase of IgAV as well as after an average of 6 months, during a follow-up visit. The interconnection between renal involvement, anthropometric measurements, epidemiological data, laboratory parameters and levels of examined biomarkers have been thoroughly evaluated., Results: The serum and urine levels of NGAL, KIM-1 and L-FABP were significantly higher in children with an acute phase of IgAV as compared to the control group (P < .001) and markedly lower during follow-up retesting in comparison with the values obtained at inclusion (P < .001). However, the concentration of none of the evaluated biomarkers correlated with nephrological indices. Among all examined parameters, only male subjects were associated with nephritis (P = .017)., Conclusions: We have established no evident association between the concentrations of NGAL, KIM-1 and L-FABP and nephritis in the course of IgAV in children. Additionally, we confirmed a significant male predominance in patients with nephritis., (© 2020 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Acute kidney injury (AKI) is a serious complication of pediatric cardiac surgery, with high morbidity and mortality. We aimed to evaluate the perioperative risk factors for AKI, and the validity of novel diagnostic urinary biomarkers after pediatric cardiac surgery. We analyzed 103 consecutive pediatric patients (≤ 18 years old), who underwent cardiac surgery. AKI was defined by ≥ 50% increase in serum creatinine levels from baseline. Urinary liver-type fatty acid binding protein (L-FABP) and neutrophil gelatinase-associated lipocalin (NGAL) were measured postoperatively at the intensive care unit (ICU) admission, subsequently at 4, 12, and 24 h. Areas under the receiver-operating characteristic curves (AUC) were calculated at each assessment time. AKI had developed in 47 patients (45.6%) by the second postoperative day. Univentricular status, aortic cross-clamping time, and intraoperative fluid balance were independently associated with AKI (p = 0.02, 0.01 and 0.01, respectively). Urinary L-FABP and NGAL were significantly higher in the AKI group at each point (p < 0.05). The predictive abilities of both biomarkers (AUC = 0.78-0.90) at ICU admission and 4 h after were especially high. The patients with L-FABP greater than the cutoff value at ICU admission and 4 h after ICU admission had significantly longer intubation and hospitalization periods (p < 0.05). Those with elevated NGAL levels at admission, and 4 h and 24 h after ICU admission, had significantly longer intubation, ICU stay, and hospitalization (p < 0.05). L-FABP and NGAL can be useful biomarkers for detecting early AKI after pediatric cardiac surgery and predicting adverse clinical outcomes.

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.)

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., (© 2017, Wiley Periodicals, Inc.)

Acute kidney injury (AKI) is one of the most common complications in critically ill patients, resulting in high morbidity and mortality. AKI usually occurs after major surgery, severe infection or drug-induced nephrotoxicity and is associated with prolonged hospital stays, increased costs and adverse clinical outcomes. The diagnosis of AKI is currently based on decreased glomerular filtration rate (GFR) and urine output, and increased serum creatinine. Novel biomarkers are required for early identification of patients with AKI to allow timely therapy and improve patient outcomes. With the advent of proteomics and genomics techniques, a vast array of biomarkers are now available in clinical practice., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objective: Hypoxia occurs following convulsions, and hypoxia is one of the most common causes of acute renal damage. The aim of this study was to investigate urinary levels of kidney injury molecules, including neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG), and liver-type fatty acid-binding protein (L-FABP) in children with febrile seizures (FS) for the first time., Methods: The study included 28 children with FS and 34 age and gender matched healthy children. Serum biochemistry and blood gases were measured in the serum samples. Estimated glomerular filtration rate (eGFR) was calculated. NGAL, NAG, L-FABP, and creatinine (Cr) were measured in the urine samples. The ratios of kidney injury markers to urinary Cr were used for comparisons., Results: There were no significant differences in eGFR and serum chemistry values between the FS and the control group (p > 0.05). Hypoxia was detected in 67.9% of the FS patients. The FS group had significantly higher urinary kidney injury molecules to Cr ratios compared to the controls, including NGAL/Cr (17.9 ± 9.8; 6.7 ± 4.0, respectively; p < 0.001), NAG/Cr (0.55 ± 0.29; 0.21 ± 0.16, p < 0.001), and L-FABP/Cr (4.85 ± 2.93; 1.74 ± 1.16, p < 0.001)., Conclusion: Increased urinary NGAL/Cr, NAG/Cr, and L-FABP/Cr values, in patients with FS compared to healthy controls, suggest a possible subclinical renal damage in these patients.

Acute kidney injury (AKI) is a common complication after coronary angiography. Early biomarkers of this disease are needed since increase in serum creatinine levels is a late marker. To assess the usefulness of urinary kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL) and liver-type fatty acid-binding protein (uL-FABP) for early detection of AKI in these patients, comparing their performance with another group of cardiac surgery patients. Biomarkers were measured in 193 patients, 12 h after intervention. In the ROC analysis, AUC for KIM-1, NGAL and L-FABP was 0.713, 0.958 and 0.642, respectively, in the coronary angiography group, and 0.716, 0.916 and 0.743 in the cardiac surgery group. Urinary KIM-1 12 h after intervention is predictive of AKI in adult patients undergoing coronary angiography, but NGAL shows higher sensitivity and specificity. L-FABP provides inferior discrimination for AKI than KIM-1 or NGAL in contrast to its performance after cardiac surgery. This is the first study showing the predictive capacity of KIM-1 for AKI after coronary angiography. Further studies are still needed to answer relevant questions about the clinical utility of biomarkers for AKI in different clinical settings.

The prevalence of type 1 cardiorenal syndrome (CRS) is increasing and strongly associated with long-term mortality. However, lack of reliable animal models and well-defined measures of renoprotection, made early diagnosis and therapy difficult. We previously successfully established the swine acute myocardial infarction (AMI) model of ischemia-reperfusion by blocking left anterior descending branch (LAD). Reperfusion was performed after 90-minute occlusion of the LAD. AMI was confirmed by ECG and left ventricular angiography (LVG). Then those 52 survived AMI reperfusion swine, including ventricular fibrillation-cardiac arrest after restoration of blood flow, were randomly divided into four groups (four/group) according to different interventions: resuscitation in room temperature, resuscitation with 500 ml saline in room temperature, resuscitation with 4°C 500 ml saline and normal control (with no intervention of resuscitation). Each group was further observed in four groups according to different time of resuscitation after ventricular arrhythmias: 1, 3, 5, 10-minute reperfusion after ventricular arrhythmias. Plasma and random urine were collected to evaluate renal function and test renal biomarkers of acute kidney injury (AKI). Our swine AMI model of ischemia-reperfusion provoked subclinical AKI with the elevation of the tubular damage biomarker, NGAL, IL-18 and L-FABP. Renal damage rapidly observed after hemodynamic instability, rather than observation after several hours as previously reported. The increasing rate of biological markers declined after interventions, however, its impact on the long-term prognosis remains to be further studied. These data show that elevation of tubular damage biomarkers without glomerular function loss may indicate appropriate timing for effective renoprotections like hypothermia resuscitation in type 1 CRS.

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Acute kidney injury (AKI) is a significant problem in children undergoing cardiopulmonary bypass (CPB). The aims of this study were to assess the diagnostic validity of serum CysC (sCysC), serum neutrophil gelatinase lipocalin (sNGAL), urine neutrophil gelatinase lipocalin (uNGAL), urine kidney injury molecule (uKIM)-1, and urine liver fatty acid-binding protein (uL-FABP) to predict AKI presence and severity in children undergoing CPB., Design and Methods: We performed a prospective single-center evaluation of sCysC, sNGAL, uNGAL, uKIM-1 and uL-FABP at 0, 2, 6, 24 and 48 h postoperatively in children undergoing CPB during cardiac surgery. AKI was defined as ≥25% decrease in the estimated creatinine clearance (eCCl) from pre-operative baseline at 48h after surgery., Results: Of the 112 patients, 18 patients (16.1%) developed AKI; four of them needed acute dialysis treatment and three AKI patients died. In the AKI compared to the non-AKI group, sCysC at 2h, and uNGAL and uL-FABP at 2-48 h were significantly increased, as well as CPB, aortic cross clamp time and length of hospital stay. Biomarkers increased with worsening AKI severity. At 2h after CPB the best accuracy for diagnosis of AKI had uL-FABP and sCysC with area under the receiver operator curve (AUC) of 0.89 and 0.73, respectively. At 6 and 24h after CPB the best AUC was found for uL-FABP (0.75 and 0.87 respectively) and for uNGAL (0.70 and 0.93, respectively)., Conclusions: sCysC, uNGAL and uL-FABP are reliable early predictors for AKI after CPB. By allowing earlier timing of injury and earlier intervention, they could improve AKI outcome., (© 2013.)

The results of published studies of modern biomarkers used in the diagnosis of acute kidney injury (AKI) were summarized. The search was carried out in the PubMed/MEDLINE, Scopus, eLibrary databases. AKI occurs in 10–15% of all inpatients and 50% of intensive care patients, and affects economic aspects of treatment and rehabilitation. The literature review allowed to draw conclusions about the significant advantage of new AKI biomarkers (cystatin C, neutrophil gelatinase-associated lipocalin, β2-microglobulin, kidney injury molecule-1, fatty acid binding protein) over the conventional glomerular filtration rate, serum creatinine and urinary volume. Serum creatinine increases only in cases when 50–60% of nephrons are damaged, urinary volume has limitations such as the overdiagnosis of AKI in dehydrated patients, the inability to assess based on a single measurement, and the need for regular and frequent follow-up. Modern biomarkers make it possible to verify renal dysfunction in advance, at the subclinical level. This allows to make a correction in the therapy of the underlying disease and initiate nephroprotection to prevent the development of AKI and the further development of multiple organ failure, which may be more effective than the treatment of already developed AKI.

Drug-induced kidney injury (DIKI) accounts for 8 to 60% of episodes of acute kidney injury (AKI) among hospital patients. Early DIKI detection and timely adjustment of therapy will help reduce the kidney injury incidence and mortality. The aim of the study was to analyse scientific literature on the biomarkers used in DIKI diagnosis. The study revealed that the use of such kidney damage markers as serum creatinine, urinary output, urea nitrogen, sodium excretion, urinary sediment microscopy is limited because they do not give a full picture of the kidney injury degree and progression and do not allow for early AKI diagnosis. It was demonstrated that some of the most promising biomarkers are KIM-1, L-FABP, NAG, NGAL, cystatin C, clusterin, β2-microglobulin, МСР-1, IGFBP7, and TIMP-2. However, recommendations for determination of these biomarkers’ urine or blood concentrations for AKI diagnosis are somewhat preliminary, because there have been insufficient clinical and preclinical studies to establish validity of such tests. No precise algorithms based on determination of the biomarkers levels in urea and/or blood serum have been developed for AKI risk assessment, diagnosis, monitoring, and treatment. Thus, further research is necessary to investigate different AKI biomarkers and improve experimental models (both in vivo and in vitro), which will support assessment of potential nephrotoxic properties of existing and new medicinal products.

Background: The most important factor in the diagnosis of AKI is to accurately and early detect the damage that occurs in the kidney before the filtration capacity of the kidney decreases. Therefore, we discussed the use of NGAL and L-FABP in the early diagnosis of acute kidney injury, evaluation of clinical severity and prognosis as well as prediction of hemodialysis decision in this prospective study. Methods: We studied 82 participants which included 41 patients aged 18 years and older with the diagnosis of acute kidney injury. We compared the renal function tests collected at 0 and 6 hours with the plasma NGAL and LFABP levels measured using ELISA. Acute kidney injury was defined as serum creatinine increase of 0.3 mg/dL in the last 48 hours, or an increase more than 1.5 times, or an increase in the basal serum creatinine value in the last seven days, or less than 0.5/mL/kg of urine volume within six hours. We tested the power of these new biomarkers in the early diagnosis, and prediction of hemodialysis and survival of the patients with AKI using ROC analysis. Results: Fifteen (36.6%) of the patients were anuric and 26 (63.4%) were oliguric. Twenty-one (51.2%) patients were KDIGO Stage 3. Seventeen (41.5%) patients underwent hemodialysis. In the patient group, the mean NGAL level was 289.7 ± 117.4 ng/mL and the mean L-FABP level was 232.7 ± 72.8. Eleven (26.9%) of 41 patients died within the first 24 hours. In the dead patients, the mean plasma NGAL level was statistically significantly high (p = 0.005). The mean NGAL level was found to be statistically increased in correlation with the severity of acute kidney injury in patients (p < 0.05). To predict acute kidney injury, the ROC analysis showed that the area under the curve (AUC) was 0.819 (95% confidence interval (CI): 0.729 - 0.909) (p < 0.001) for plasma NGAL level, and the area under the curve (AUC) was 0.891 (95% confidence interval (CI): 0.822 - 0.959) for plasma L-FABP level (p < 0.001). Conclusions: Our study provides evidence that NGAL and L-FABP are effective biomarkers for early detection of AKI as well as predicting clinical severity and hemodialysis. [ABSTRACT FROM AUTHOR]

Purpose: We examined the clinical utility of perioperative monitoring of urinary liver-type fatty acid binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), and albumin, for prediction of acute kidney injury (AKI) and prediction of chronic renal dysfunction in patients undergoing open surgical repair (OSR) of an abdominal aortic aneurysm. Patients and Methods: Urine and serum samples were obtained perioperatively from 64 such patients (n=64). Patients in whom OSR-related AKI (defined by the Kidney Disease Improving Global Outcomes criteria) occurred were identified. Renal function was evaluated 3 years after OSR in patients with OSR-related AKI. Results: The urinary biomarkers examined increased to maximum levels by 2 hours after aortic cross-clamping (AXC), regardless of whether AKI occurred. Notably, the serum creatinine (Cr) levels increased significantly immediately after OSR in patients with AKI (n=19) (vs that in patients without AKI). In patients with AKI, the increased serum Cr elevation rate, the urinary L-FABP levels 2 hours after AXC and immediately after OSR, and a reduction in eGFR documented 3 years after OSR were significantly greater in patients who underwent suprarenal AXC (n=11) than in those who underwent infrarenal AXC (n=8). Furthermore, urinary L-FABP levels 2 hours after AXC correlated significantly with the reductions in eGFR 3 years after OSR in patients with AKI. Conclusion: Urinary L-FABP, NGAL and albumin concentrations 2 hours after AXC may be useful for early detection of OSR-related AKI. Furthermore, the increase in urinary L-FABP 2 hours after AXC may be predictive of chronic renal dysfunction in patients with OSR-related AKI. [ABSTRACT FROM AUTHOR]

Abstract 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

Background: Acute tubular necrosis (ATN) describes a form of intrinsic acute kidney injury (AKI) that results from persistent hypoperfusion and subsequent activation of the immune system. A glycosylated transmembrane protein, CD147/basigin, is involved in the pathogenesis of renal ischemia and fibrosis. The present study investigated whether CD147 can reflect pathological features and renal dysfunction in patients with AKI. Methods: Plasma and spot urine samples were collected from 24 patients (12 controls and 12 with ATN) who underwent renal biopsy between 2008 and 2012. In another study, patients undergoing open surgery to treat abdominal aortic aneurysms (AAAs) were enrolled in 2004. We collected urine and plasma samples from seven patients with AKI and 33 patients without AKI, respectively. In these experiments, plasma and urinary CD147, and urinary l-fatty acid-binding protein ( l-FABP) levels were measured, and the former expression in kidneys was examined by immunostaining. Results: In biopsy tissues of ATN with severe histological features, CD147 induction was strikingly present in inflammatory cells such as macrophages and lymphocytes in the injured interstitium, but not in damaged tubules representing atrophy. Both plasma and urinary CD147 levels were strikingly increased in ATN patients; both values showed greater correlations with renal dysfunction compared to urinary l-FABP. In patients who had undergone open AAA surgery, urinary and plasma CD147 values in AKI patients were significantly higher than in non-AKI patients at post-operative day 1, similar to the profile of urinary l-FABP. Conclusion: CD147 was prominent in its ability to detect AKI and may allow the start of preemptive medication. [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]

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]