Diagnostic Performance of Fas Ligand mRNA Expression for Acute Rejection after Kidney Transplantation: A Systematic Review and Meta-Analysis.

BACKGROUND: The value of Fas ligand (FASL) as a diagnostic immune marker for acute renal rejection is controversial; this meta-analysis aimed to clarify the role of FASL in acute renal rejection. METHODS: The relevant literature was included by systematic searching the MEDLINE, EMBASE, and Cochrane Library databases. Accuracy data for acute rejection (AR) and potential confounding variables (the year of publication, area, sample source, quantitative techniques, housekeeping genes, fluorescence staining, sample collection time post-renal transplantation, and clinical classification of AR) were extracted after carefully reviewing the studies. Data were analyzed by Meta-DiSc 1.4, RevMan 5.0, and the Midas module in Stata 11.0 software. RESULTS: Twelve relevant studies involving 496 subjects were included. The overall pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, and diagnostic odds ratio, together with the 95% CI were 0.64 (0.57-0.70), 0.90 (0.85-0.93), 5.66 (3.51-9.11), 0.30 (0.16-0.54), and 30.63 (14.67-63.92), respectively. The area under the summary receiver operating characteristic curve (AUC) was 0.9389. Fagan's nomogram showed that the probability of AR episodes in the kidney transplant recipient increased from 15% to 69% when FASL was positive, and was reduced to 4% when FASL was negative. No threshold effect, sensitivity analyses, meta-regression, and subgroup analyses based on the potential variables had a significant statistical change for heterogeneity. CONCLUSIONS: Current evidence suggests the diagnostic potential for FASL mRNA detection as a reliable immune marker for AR in renal allograft recipients. Further large, multicenter, prospective studies are needed to validate the power of this test marker in the non-invasive diagnosis of AR after renal transplantation.

Chronic reactive oxygen species exposure inhibits glucose uptake and causes insulin resistance in C2C12 myotubes.

Reactive oxygen species (ROS) is an important regulator in cellular signaling transduction, and many previous studies have indicated that acute ROS stimulation improves insulin sensitivity in skeletal muscle. In the study, we found that chronic ROS treatment caused serious insulin resistance in C2C12 myotubes. Glucose uptake and consumption assay indicated that pretreatment with 80 µM H2O2 for 2 h inhibited insulin-stimulated glucose uptake in C2C12 myotubes, and the reason for it, is that chronic H2O2 treatment decreased insulin-induced glucose transporter 4 (GLUT4) translocation from cell plasma to cell membrane. Moreover, Akt2 phosphorylation depended on insulin was reduced in C2C12 myotubes of chronic H2O2 treatment. Together, this study provides further demonstration that chronic ROS stress is associated with insulin resistance of skeletal muscle in the progression of type 2 diabetes.

The relationship between transforming growth factor beta1 expression and cold ischemia injury of rat donor kidney.

OBJECTIVE: Cold ischemia injury represents an independent risk factor which favors chronic allograft nephropathy (CAN). In order to investigate the role of transforming growth factor-beta 1( (TGF-beta1) in the progression of CAN, we studied the relationship between the expression of TGF-beta1 and cold ischemia injury in the renal tubular epithelia of rat donor kidney. METHODS: A total of 24 Wistar rats were used in this study. In terms of the time of cryopreservation of donor kidney, the 24 Wistar rats were randomly divided into 3 groups: 0 h group(control group), 24 h group, 48 h group. A block removal of donor kidney with in situ perfusion of cooling HC-A preservation solution was adopted. The rat kidney was preserved 0 h, 24h and 48 h at 0-4 degrees C respectively. The morphologic changes of proximal tubular epithelial cells in different cryopreservation time were observed under light microscope and transmission electron microscope. The expression of TGF-beta1 mRNA and protein in proximal tubular epithelial cells of different cryopreservation time group were detected by in situ hybridization and immunohistochemistry analysis. RESULTS: 1. In 24 h group, part of the proximal tubular epithelial cells showed slight degeneration. In 48 h group, the proximal tubular epithelial cells demonstrated severe hydropic degeneration and part of the cells developed necrosis and effluxion. 2. Only a small amount of TGF-beta1 protein and mRNA were expressed in the renal tubular epithelial cells of 0 h group. The positive unit (PU) value of TGF-beta1 protein and mRNA were 6.37+/-2.77 and 5.29+/-2.15, respectively. As the cold ischemia time prolonged, the PU value of TGF-beta1 protein increased at 24 h group (10.20+/-3.27) and 48 h group (17.17+/-3.96) . The PU value of TGF-beta1 mRNA also increased at 24 h group (11.31+/-3.34) and 48 h group (19.01+/-3.53). There was the significant difference of TGF-beta1 protein PU value or mRNA PU value among these groups(P<0.05). CONCLUSION: There was the significant correlation between the expression of TGF-beta1 and the degree of cold ischemia injury. The results suggest that TGF-beta1 might play the key role in regeneration and reparation of renal tubular epithelial cell injury. The overexpression of TGF-beta1 might be one of the mechanisms that initiate chronic allograft nephropathy.

[Effects of cryopreservation on expression of connective tissue growth factor in rat kidney].

OBJECTIVE: To investigate the effect of cryopreservation (CP) on the expression of connective tissue growth factor (CTGF) in the renal tubular epithelial cells. METHODS: A total of 40 male Wistar rats (weighing 230-250 g) were used in this study. En bloc removal with in situ cooling both kidneys and hypertonic citrate adenine preservation solution were adopted. The rat kidney was be preserved 0, 12, 24, 36 and 48 hours at 0-4 degrees C (n=8), respectively. The expression of CTGF of renal tubular epithelial cells was detected by using immunohistochemistry and in situ hybridization analysis. RESULTS: The expression of CTGF was less in CP 0 hour group and CP 12 hours group, the positive unit (PU) values of CTGF protein were 5.91 +/- 2.30 and 5.57 +/- 2.40 (P > 0.05), respectively, and the PU values of CTGF mRNA were 6.24 +/- 2.79 and 6.51 +/- 2.43 (P > 0.05), respectively. The PU values of CTGF protein increased at CP 24 hours group (10.25 +/- 2.92), CP 36 hours group (14.31 +/- 2.83) and CP 48 hours group (18.11 +/- 3.94, P < 0.05), respectively, and the PU values of CTGF mRNA increased at CP 24 hours group (15.24 +/- 3.95), CP 36 hours group (19.20 +/- 4.73) and CP 48 hours group (23.09 +/- 4.40, P < 0.05), respectively; showing significant differences when compared with CP 0 hour group and CP 12 hours group (P < 0.05). CONCLUSION: CTGF expression may increase with severe cold ischemia injury, and might play an important role in regeneration and repair of renal tubular epithelial cell injury.