Clinical application of biomarkers in DCD donor kidney perfusate for predicting delayed graft function after renal transplantation / 器官移植

Objective To explore the feasibility of biomarkers in static cold storage (SCS) perfusate of donor kidney from donation after cardiac death (DCD) for predicting delayed graft function (DGF) after renal transplantation. Methods Clinical data of 64 recipients and 47 donors undergoing DCD renal transplantation were retrospectively analyzed. All recipients were divided into the DGF group (n=7) and immediate graft function (IGF) group (n=57) according to the incidence of postoperative DGF in the recipients. The levels of neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), interleukin -18(IL-18) and kidney injury molecule-1 (KIM-1) in the SCS perfusate were statistically compared between two groups, and the correlation with DGF was analyzed. The predictive value of each biomarker in the occurrence of DGF in recipients after renal transplantation was analyzed. Results The incidence of DGF in the recipients undergoing DCD renal transplantation was 11% (7/64). The NGAL level in the donor kidney perfusate of the DGF group was significantly higher than that in the IGF group (P=0.009). The NGAL level in the donor kidney perfusate was positively correlated with the incidence of DGF in recipients after renal transplantation (r=0.430, P < 0.001). The receiver operating characteristic (ROC) curve analysis showed that the increased levels of NGAL and KIM-1 in the perfusate yielded certain predictive value for DGF in recipients after renal transplantation (both P < 0.05). The area under the curve (AUC) of combined detection of NGAL and KIM-1 for predicting DGF in recipients after renal transplantation was 0.932 [95% confidence interval (CI) 0.850-1.000]. The sensitivity was calculated as 1.000 and 0.754 for the specificity (P < 0.05). Conclusions The NGAL level in the SCS perfusate of DCD donor kidney is associated with the occurrence of DGF in recipients after renal transplantation. Combined detection of NGAL and KIM-1 levels in the perfusate may accurately predict the occurrence of DGF in recipients after renal transplantation.

The value of combined detection of serum CysC, urinary β2-MG, and L-FABP in early diagnosis of acute renal injury after cardiac surgery / 中国医师杂志

Objective@#To explore the value of combined detection of serum cystatin C (CysC), urinary β2-microglobulin (β2-MG), and liver type fatty acid binding protein (L-FABP) in early diagnosis of acute renal injury after cardiac surgery.@*Methods@#126 patients undergoing cardiac surgery in our hospital from April 2015 to August 2016 were selected as the subjects, according to the occurrence of acute renal injury after operation, 48 cases were divided into acute renal injury (AKI) group and 78 cases into non-acute renal injury (non AKI) group, the levels of serum CysC, urine β2-MG, and L-FABP were detected in the two groups. Receiver operating characteristic (ROC) curve was used to analyze the effects of serum CysC, urine β2-MG, L-FABP in the early diagnosis of acute renal injury after cardiac surgery.@*Results@#The incidence of AKI after cardiac surgery was 38.10% (48/126); the serum CysC level in group AKI was significantly higher than that in non AKI group (P<0.05); the levels of urine β2-MG and L-FABP were significantly higher than those in non AKI group (P<0.05); the area under curve (AUC) of serum CysC for AKI diagnosis after cardiac surgery was 0.874 (P<0.05), with diagnostic sensitivity 85.7%, and specificity 76.5%; the AUC area of urinary β2-MG for AKI diagnosis after cardiac surgery was 0.754 (P<0.05), with diagnostic sensitivity 92.9%, and specificity 73.5%, respectively; the AUC area of urinary L-FABP for AKI diagnosis after cardiac surgery was 0.834 (P<0.05), with diagnostic sensitivity 92.9%, and specificity 74.1%. The AUC area of combined diagnosis of the three was 0.914 (P<0.05), with the diagnostic sensitivity 92.1%, and specificity 82.4%.@*Conclusions@#Serum Cys C, urine β 2-MG and L-FABP levels were significantly increased in patients with AKI. The diagnosis of the three alone has a certain reference value, which is lower than the combined diagnosis. The combined diagnosis of the three can provide an important reference for screening acute renal injury after heart surgery.

The associations of Urinary Neutrophil Gelatinaseassociated Lipocalin (NGAL) and Liver-type Fatty Acidbinding Protein (L-FABP) Levels with Hematuria in Children and Adolescents

PURPOSE: We sought to determine associations of urinary neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP), known markers of renal injury, with hematuria in children and adolescents.METHODS: A total of 112 urine samples from 72 patients aged 2 to 18 years with hematuria were enrolled in this study. Urinary concentrations of NGAL and L-FABP were measured by ELISA and compared between subjects with and without proteinuria and between subjects with and without glomerulonephritis diagnosed by renal biopsy.RESULTS: Urinary concentrations of NGAL and L-FABP/creatinine (Cr) in subjects with proteinuria were not significantly different from those in subjects without proteinuria. They were not significant different between subjects with and without glomerulonephritis either. However, both concentrations of urinary NGAL and L-FABP/Cr were positively associated with urinary protein to creatinine ratio. Their levels had a tendency to be increased when proteinuria developed at later visits in subjects with hematuria only at initial visits.CONCLUSION: Monitoring urinary NGAL and L-FABP levels in addition to conventional risk factors such as proteinuria and serum creatinine might improve the prediction of renal injury in pediatric patients with hematuria.

The value of combined detection of serum CysC, urinary β2-MG, and L-FABP in early diagnosis of acute renal injury after cardiac surgery / 中国医师杂志

Objective To explore the value of combined detection of serum cystatin C (CysC),urinary β2-microglobulin (β2-MG),and liver type fatty acid binding protein (L-FABP) in early diagnosis of acute renal injury after cardiac surgery.Methods 126 patients undergoing cardiac surgery in our hospital from April 2015 to August 2016 were selected as the subjects,according to the occurrence of acute renal injury after operation,48 cases were divided into acute renal injury (AKI) group and 78 cases into non-acute renal injury (non AKI) group,the levels of serum CysC,urine β2-MG,and L-FABP were detected in the two groups.Receiver operating characteristic (ROC) curve was used to analyze the effects of serum CysC,urine β2-MG,L-FABP in the early diagnosis of acute renal injury after cardiac surgery.Results The incidence of AKI after cardiac surgery was 38.10％ (48/126);the serum CysC level in group AKI was significantly higher than that in non AKI group (P ＜ 0.05);the levels of urine β2-MG and L-FABP were significantly higher than those in non AKI group (P ＜ 0.05);the area under curve (AUC) of serum CysC for AKI diagnosis after cardiac surgery was 0.874 (P ＜ 0.05),with diagnostic sensitivity 85.7％,and specificity 76.5％;the AUC area of urinary β2-MG for AKI diagnosis after cardiac surgery was 0.754 (P ＜0.05),with diagnostic sensitivity 92.9％,and specificity 73.5％,respectively;the AUC area of urinary L-FABP for AKI diagnosis after cardiac surgery was 0.834 (P ＜ 0.05),with diagnostic sensitivity 92.9％,and specificity 74.1％.The AUC area of combined diagnosis of the three was 0.914 (P ＜0.05),with the diagnostic sensitivity 92.1％,and specificity 82.4％.Conclusions Serum Cys C,urine β 2-MG and LFABP levels were significantly increased in patients with AKI.The diagnosis of the three alone has a certain reference value,which is lower than the combined diagnosis.The combined diagnosis of the three can provide an important reference for screening acute renal injury after heart surgery.

Early diagnosis of acute kidney injury in aged patients undergoing percutaneous coronary intervention / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

In aged patients, acute kidney injury (AKI) is a common clinical complication after percutaneous coronary intervention (PCI), highlighting the need for timely and certain diagnosis of this disease. A single centre, nested case-control study was conducted, which assessed the usefulness of urinary liver-type fatty acid-binding protein (uL-FABP), neutrophil gelatinase-associated lipocalin (uNGAL), and kidney injury molecule-1 (uKIM-1) for early detection of AKI. One hundred and thirty-two patients at or over 60 years old undergoing PCI were included. Serum creatinine (SCr) was measured before PCI, 24 and 48 h after PCI; uL-FABP, uNGAL, and uKIM-1 were measured before PCI, 6, 24, and 48 h after PCI. We identified 16 AKI patients and selected 32 control patients matched by admission time (<1 week), age (±5 years), and gender. In the receiver operating characteristic (ROC) curve analysis, the areas under the curve (AUCs) for the relative measurements of uL-FABP, uNGAL, and uKIM-1 were 0.809, 0.867, and 0.512 at 6 h after PCI, and 0.888, 0.840, and 0.676 at 24 h after PCI, respectively. AUC for the combination of uL-FABP and uNGAL was 0.899 at 6 h after PCI, and 0.917 at 24 h after PCI. Thus, measurement of uL-FABP and uNGAL levels at 6 and 24 h after PCI may be useful in detecting AKI in aged patients. Measurement of uKIM-1 levels provides inferior predictive power for early diagnosis of AKI.

Diagnostic value of combined detection of NGAL,L-FABP and KIM-1 in urine for early acute kidney injury in children / 国际检验医学杂志

Objective To investigate the diagnostic value of combined detection of NGAL,L-FABP and KIM-1 in urine for early acute kidney injury in children.Methods 128 cases sepsis patients in our hospital during ICU from September 2015 to September 2016 were enrolled in the study,according to the occurrence of acute renal injury(AIK)were divided into observation group and control group,the incidence of AKI in 26 ca-ses as the observation group,102 cases without AKI as control group;the content of urine collected from two groups of children,NGAL L-FABP,KIM-1.Results In AKI group 6 h NGAL,L-FABP,Kim-1 in urine in-creased significantly higher than that of the other time points and non AKI group level,significant difference was statistically significant;6h NGAL,L-FABP,Kim-1 in urine combined detection efficiency is highest,sen-sitivity,specificity and positive pre detection value and negative predictive value were measured 86.7%,97. 8%,78.3% a,98.7% a,was significantly higher than the diagnostic efficacy of urinary NGAL,L-FABP,Kim-1;6h,L-FABP,NGAL in the urine level of KIM-1 and 48h in patients with creatinine and GFR levels of correla-tion analysis found that in children with early urinary NGAL,L-FABP,KIM-1 and 48h in children with creati-nine and GFR levels were positive related.Conclusion The detection of NGAL,L-FABP and KIM-1 in urine is of great significance in the diagnosis of AKI in children,which is worthy of clinical application.

Cytokine-like Activity of Liver Type Fatty Acid Binding Protein (L-FABP) Inducing Inflammatory Cytokine Interleukin-6

It has been reported that fatty acid binding proteins (FABPs) do not act only as intracellular mediators of lipid responses but also have extracellular functions. This study aimed to investigate whether extracellular liver type (L)-FABP has a biological activity and to determined serum L-FABP levels in patients with end-stage renal disease (ESRD). We isolated L-FABP complementary deoxyribonucleic acid (cDNA) from the Huh7 human hepatocarcinoma cell line and expressed the recombinant L-FABP protein in Escherichia coli. A549 lung carcinoma and THP-1 monocytic cells were stimulated with the human recombinant L-FABP. Human whole blood cells were also treated with the human recombinant L-FABP or interleukin (IL)-1α. IL-6 levels were measured in cell culture supernatants using IL-6 enzyme-linked immunosorbent assay (ELISA). Human recombinant L-FABP induced IL-6 in a dose-dependent manner in A549, THP-1 cells, and whole blood cells. The blood samples of healthy volunteers and patients with ESRD were taken after an overnight fast. The serum levels of L-FABP in healthy volunteers and ESRD patients were quantified with L-FABP ELISA. The values of L-FABP in patients with ESRD were significantly lower than those in the control group. Our results demonstrated the biological activity of L-FABP in human cells suggesting L-FABP can be a mediator of inflammation.

Acute Kidney Injury after Using Contrast during Cardiac Catheterization in Children with Heart Disease

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.

The Role of Urinary Liver-Type Fatty Acid-Binding Protein in Critically Ill Patients

Although several urinary biomarkers have been validated as early diagnostic markers of acute kidney injury (AKI), their usefulness as outcome predictors is not well established. This study aimed to determine the diagnostic and prognostic abilities of urinary liver-type fatty acid-binding protein (L-FABP) in heterogeneous critically ill patients. We prospectively collected data on patients admitted to medical and surgical intensive care units (ICUs) from July 2010 to June 2011. Urine neutrophil gelatinase-associated lipocalin (NGAL) and L-FABP at the time of ICU admission were quantitated. Of the 145 patients, 54 (37.2%) had AKI defined by the Acute Kidney Injury Network (AKIN) criteria. AKI patients showed significantly higher level of urinary NGAL and L-FABP and also higher mortality than non-AKI patients. The diagnostic performances, assessed by the area under the ROC curve, were 0.773 for NGAL and 0.780 for L-FABP, demonstrating their usefulness in diagnosing AKI. In multivariate Cox analysis, urinary L-FABP was an independent predictor for 90-day mortality. Urinary L-FABP seems to be promising both for the diagnosis of AKI and for the prediction of prognosis in heterogeneous ICU patients. It needs to be further validated for clinical utility.

Early biomarkers for acute kidney injury / 中国小儿急救医学

Acute kidney injury (AKI) represents a common and devastating problem in clinical medicine. The lack of early biomarkers for AKI has led to a delay in initiating potentially effective therapies.Identification of novel biomarkers for AKI has progressed to the clinical phase of the biomarker discovery process. The most promising AKI biomarkers include neutrophil gelatinase-associated lipocalin, IL-18, kidney injury molecule-1 and liver-type fatty acid binding protein. In this article, we review the study of neutrophil gelatinase-associated lipocalin,IL-18, kidney injury molecule-1 and liver-type fatty acid binding protein in recent years,in order to provide the theory basis for the clinical application of the early biomarkers for AKI.