Research progress on molecular markers related to the donor kidney injury from organ donation after citizen's death / 器官移植

Shortage of donor kidney is a major problem in renal transplantation. Accurate evaluation of donor kidney function may reduce the organ rejection rate and save more patients with uremia. Compared with pathological examination, detection of circulating molecular markers is more convenient in clinical application. In this article, the research progress on the markers of kidney injury, such as serum creatinine, serum cystatin C (Cys-C), neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), mitochondrial DNA (mtDNA), kidney injury molecule-1(KIM-1) and interleukin -18 (IL-18), were briefly reviewed.

Expression and significance of L-FABP in hilar cholangiocarcinoma / 中华消化外科杂志

Objective To explore the expression of liver fatty acid binding protein (L-FABP) in tissues of hilar cholangiocarcinoma and the relationship between expression of L-FABP and clinicopathological factors and prognosis of the patients.Methods The retrospective case-control study was conducted.The clinicopathological data of 132 patients with hilar cholangiocarcinoma who were admitted to the Navy General Hospital between January 2003 and January 2013 were collected.The expression of L-FABP in tumor tissues and adjacent tissues of hilar cholangiocarcinoma and normal bile duct tissues were respectively detected by immunohistochemistry.Observation indicators:(1) expression of L-FABP by immunohistochemistry;(2) relationship between clinicopathological factors of patients and expression of L-FABP in tumor tissues;(3) follow-up and survival situations;(4) prognostic analysis of patients after radical resection of hilar cholangiocarcinoma.Follow-up using outpatient examination and telephone interview was performed to detect postoperative overall survival time up to June 2017.Count data were described as percentage and compared using the chi-square test.The survival time was calculated by the Kaplan-Meier method.Measurement data with skewed distribution were described as M (range).The univariate analysis and multivariate analysis were respectively done using the nonparametric test and COX regression model.Results (1) Expression of L-FABP by immunohistochemistry:the positive expressions of L-FABP were located in the cytoplasm.The low,moderate and high expression rates of L-FABP in tumor tissues were respectively 11.36％ (15/132),71.97％ (95/132) and 16.67％ (22/132),and positive-staining cells showed platy and / or diffuse distribution;the low,moderate and high expression rates of L-FABP in adjacent tissues of hilar cholangiocarcinoma were respectively 77.27％ (102/132),7.58％ (10/132) and 15.15％ (20/132),and positive-staining cells showed scattered or platy distribution,with a weaker staining intensity compared with tumor tissues;there was no positive expression in normal bile duct tissues.There was a statistically significant difference in expressions of L-FABP among tumor tissues and adjacent tissues of hilar cholangiocarcinoma and normal bile duct tissues (x2=5.423,P ＜ 0.05).(2) Relationship between clinicopathological factors of patients and expression of L-FABP in tumor tissues:cases with low,moderate and high expressions of L-FABP in tumor tissues were respectively 10,30,5 in 45 patients with tumor diameter ＜ 3 cm and 4,29,9 in 42 patients with 3 cm ≤ tumor diameter ≤ 5 cm and 1,36,8 in 45 patients with tumor diameter ＞ 5 cm,with a statistically significant difference (x2 =10.171,P＜ 0.05).(3) Follow-up and survival situations:132 patients were followed up for 5-90 months,with a median time of 33 months.During the followup,postoperative overall median survival time of 132 patients was 31 months.(4) Prognostic analysis of patients after radical resection of hilar cholangiocarcinoma:results of univariate analysis showed that tumor differentiation,lymph node metastasis and expressions of L-FABP in tumor tissues were related factors affecting prognosis of patients after radical resection of hilar cholangiocarcinoma (Z =1.845,3.156,1.243,P＜0.05).Results of multivariate analysis showed that tumor differentiation,lymph node metastasis and expressions of L-FABP in tumor tissues were independent factors affecting prognosis of patients after radical resection of hilar cholangiocarcinoma (odds ratio =0.431,1.806,3.692,95％ confidence interval:0.292-0.693,0.974-2.973,1.875-11.364,P＜0.05).Conclusions The high expression of L-FABP in tumor tissues is significantly correlated with the tumor diameter.Tumor differentiation,lymph node metastasis and expressions of L-FABP in tumor tissues are independent factors affecting prognosis of patients after radical resection of hilar cholangiocarcinoma.

Loss of Liver Fatty Acid Binding Protein Expression in Hepatocellular Carcinomas is Associated with a Decreased Recurrence-Free Survival

BACKGROUND/AIMS: Loss of liver fatty acid binding protein (LFABP) expression by immunohis-tochemistry is a useful marker for the identification of hepatocyte nuclear factor 1alpha (HNF1alpha)-inactivated hepatocellular adenomas; however, the expression status of LFABP in hepatocel-lular carcinomas (HCCs) is still unclear. We aimed to investigate the expression status of LFABP in HCCs and examine the clinicopathological characteristics of LFABP-negative HCCs. METHODS: Immunohistochemical stains LFABP, K19 (mouse monoclonal, Dako, Glostrup, Den-mark) and EpCAM (mouse monoclonal, Calbiochem, Darmstadt, Germany) were performed on tissue microarray sections from 188 surgically resected HCCs, and the association between LFABP expression status and the clinicopathological features, survival and "stemness"-related marker expression status were analyzed. RESULTS: Loss of LFABP expression was noted in 30 (16%) out of 188 HCCs. LFABP-negative HCCs were associated with a decreased recurrence-free survival (LFABP-negative: 17.0 +/- 4.84 months [95% confidence interval [CI]: 7.5-26.5 months] versus LFABP-positive: 51.0 +/- 8.7 months [95% CI: 34.0-68.0 months]; P=0.004). HCCs with LFABP expression loss were more frequently larger and showed more frequent vascular invasion, although not statistically sig-nificant; and an inverse correlation was seen between LFABP expression and K19 expression status (P=0.001). CONCLUSIONS: Loss of LFABP expression is seen in HCCs, and is associated with a decreased recurrence-free survival.

Value of urinary L-FABP and NGAL in the diagnosis of acute kidney injury caused by obstructive nephropathy and the prediction of renal outcome / 中华肾脏病杂志

Objective To evaluate the values of urinary liver-fatty acid binding protein (uL-FABP) and urinary neutrophil gelatinase-associated lipocalin (uNGAL) in diagnosis of acute kidney injury (AKI) caused by obstructive nephropathy and in the prediction of renal prognosis.Methods Clinical data of 30 patients with obstructive nephropathy were collected prospectively.uL-FABP and uNGAL were measured by ELISA at various time points.Risk factors of the renal outcome were evaluated.The patients were followed up for at least one year.Results Patients with AK1 had higher levels of uL-FABP and uNGAL compared to those without AKI [700.00(154.62-1216.14) μg/g· Cr vs 26.90 (16.77-41.38) μg/g·Cr; 1266.69 (671.57-3396.07) μg/g·Cr vs 179.12 (90.98-215.16) μg/g·Cr,all P ＜ 0.01].Positive correlations of uL-FABP and uNGAL with serum creatinine were found (r =0.552,0.553,all P ＜ 0.01).The AUCs of uL-FABP and uNGAL to detect AKI were 0.925 and 0.900.Patients with non complete renal recovery had higher levels of uL-FABP before operation and 72-hour after operation compared to those with complete renal recovery (all P ＜ 0.01).Before operation,the AUC of uL-FABP to detect renal prognosis was 0.948,sensitivity was 85.7％ and specificity was 90.9％.72-hour after operation,the AUC of uL-FABP to detect renal prognosis was 0.935,sensitivity was 85.7％ and specificity was 90.9％.Kaplan-Meier analysis revealed that uL-FABP before operation over 366.57 μg/g · Cr or uL-FABP 72-hour after operation over 223.60 μg/g · Cr were closely related to the poor progression of renal function.Conclusions uL-FABP and uL-NGAL have good accuracy in detecting AKI.The level of uL-FABP before operation and 72-hour after operation is helpful to predict the renal outcome of obstructive nephropathy.