Urinary N-acetyl-ß-d-glucosaminidase-creatine ratio is a valuable predictor for advanced diabetic kidney disease.

BACKGROUND: Many biomarkers show high diagnostic values for diabetic kidney disease (DKD), but fewer studies focus on the predictive assessment of DKD progression by blood and urinary biomarkers. AIM: This study aims to find powerful risk predictors and identifying biomarkers in blood and urine for DKD progression. METHODS: A total of 117 patients with type 2 DKD including early and advanced stages and their laboratory parameters were statistically assessed. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the significance of discriminating between early and advanced DKD, and the predictive power for advanced DKD was analyzed by regression analysis and trisector grouping. RESULTS: N-acetyl-ß-d-glucosaminidase-creatine (NAG/CR) level in advanced DKD was statistically higher than that in early DKD (p < 0.05), and there was a higher incidence of advanced DKD (72% vs. 56%) and high odds ratio (OR: 3.917, 95% CI: 1.579-10.011) of NAG/CR with ≥2.79 U/mmol compared with <2.79 U/mmol (p < 0.05). NAG/CR ratio also showed a higher area under the ROC curve of 0.727 (95% CI: 0.616-0.828, p = 0.010) with a high sensitivity (0.75) and a moderate specificity (0.66) when 1.93 U/mmol was set as the optimal cutoff value. The adjusted-multivariable analysis revealed that NAG/CR had an OR of 1.021 (95% CI: 1.024-1.038) and 2.223 (95% CI: 1.231-4.463) based on a continuous and categorical variable, respectively, for risk of advanced DKD. Moreover, the prevalence of advanced DKD exhibited an increasing tendency by an increment of the trisector of NAG/CR. CONCLUSIONS: This study suggests that NAG/CR ratio is an independent predictor for advanced DKD, and it also can be used as a powerful identifying marker between early and advanced DKD.

Role of Th22 Cells in Human Viral Diseases.

Naive CD4+ T cells can differentiate into different cell subsets after receiving antigen stimulation, which secrete corresponding characteristic cytokines and thereby exert biological effects in various diseases. Th22 cells, a novel subset of CD4+ T cells, are different from Th1, Th2, Th17, and Treg cell subsets, which have been discovered in recent years. They can express CCR4, CCR6, and CCR10 molecules and secrete IL-22, IL-13, and TNF-α. They are not able to secrete IL-17, IL-4, and interferon-γ (IFN-γ). IL-22 is considered as a major effector molecule of Th22 cells whose functions and mechanisms of regulating cell differentiation have been constantly improved. In this review, we provide an overview of the origin, differentiation of Th22 cells. Moreover, we also describe the interrelationships between Th22 cells and Th17, Th1, and Th2 cells. Additionally, the role of Th22 cells were discussed in human diseases with virus infection, which will provide novel insight for the prevention and treatment of viral infection in human.

Krüppel­like factor 4 ameliorates diabetic kidney disease by activating autophagy via the mTOR pathway.

Diabetic kidney disease (DKD) is diagnosed increasingly frequently and represents a serious threat to human health. Krüppel­like factor 4 (KLF4) has aroused attention due to its potential effect on podocytes and in ameliorating proteinuria associated with glomerulopathy. The purpose of the present study was to investigate the potential role of KLF4 in DKD. It was hypothesized that KLF4 impacts diabetic nephropathy by mediating the podocyte autophagic process. A KLF4 plasmid vector was constructed, and podocytes were transfected and incubated with DKD mice serum for in vitro experiments. A db/db spontaneous DKD mouse model was also established for in vivo study. After treatment, the level of serum creatinine (Scr), blood urea nitrogen (BUN), and 24­h urinary protein was determined. Immunofluorescence and periodic acid­Schiff staining, western blotting, flow cytometry and a TUNEL assay were performed to observe changes in glomerular morphology and the level of apoptosis, cytoskeleton proteins, epithelial­mesenchymal transition (EMT) biomarkers, autophagic proteins and mTOR pathway proteins in each group. KLF4 overexpression significantly reduced the level of urinary albumin, Scr, BUN and attenuated mesangial matrix expansion, as well as mesangial cell proliferation in DKD mice. KLF4 overexpression also inhibited podocyte apoptosis and downregulated vimentin and α­smooth muscle actin, and upregulated E­cadherin and nephrin, both in vivo and in vitro. Moreover, the microtubule associated protein 1 light chain 3α (LC3)­II/LC3­I ratio and LC3­II fluorescence was significantly increased in the vector­KLF4 group compared to the negative control vector group both in vivo and in vitro. Finally, a decrease in the level of phosphorylated (p)­mTOR and p­S6K protein expression was observed following KLF4 overexpression in vitro. The present findings suggested that KLF4 plays a renoprotective role in DKD, which is associated with the activation of podocyte autophagy, and may be involved in the mTOR signaling pathway.

Tripterygium glycoside protects diabetic kidney disease mouse serum-induced podocyte injury by upregulating autophagy and downregulating ß-arrestin-1.

BACKGROUND: Diabetic kidney disease (DKD), one of the most common causes of end-stage renal disease(ESRD), remains prevalent in many populations. Podocyte loss and apoptosis play a crucial role in the progression of DKD. Tripterygium glycoside (TG), a widely used Chinese herb, exerted comprehensive protective effects on preventing DKD progression. This study was performed to assess the podocyte protective effect of tripterygium glycoside on DKD by the potential role of activation of autophagy and downregulating ß-arrestin-1. METHODS: Tripterygium glycoside and small interfering RNA (siRNA) of ß-arrestin-1 were added to 10% db/db mice high-glucose serum induced podocytes in vitro. Autophagic activity was evaluated by transmission electronic microscopy, immunofluorescence staining and western blot analysis. Apoptotic activity was evaluated by Annexin V-FITC/PI flow cytometric analysis. The levels of nephrin and podocin, a marker protein of podocytes, were examined using western blot analysis. RESULTS: Significantly ameliorated podocyte apoptosis, increased nephrin and podocin levels and inhibited expression of ß-arrestin-1 were observed after pretreatment of tripterygium glycoside in DKD mouse serum treated podocytes. Significantly higher levels of autophagic activity were also observed. Silencing ß-arrestin-1 upregulated autophagic activity and ameliorated podocyte apoptosis. Silencing ß-arrestin-1 in combination with tripterygium glycoside enhanced the levels of LC3-II and LC3-II/LC3-I ratios and reduced the expression of p62. Finally, we observed a notable reduction in podocyte apoptotic rate in DKD serum + siRNA-ß-arrestin-1 + TG group compared to DKD serum + siRNA-ß-arrestin-1 group, and upregulated protein levels of nephrin and podocin compared to treatment with siRNA-ß-arrestin-1 only. CONCLUSIONS: This study demonstrated that tripterygium glycoside provided protection against podocyte injury induced by high-glucose serum, and that this effect was mediated by the concomitant activation of autophagy and downregulation of ß-arrestin-1.

Association of podocyte autophagosome numbers with idiopathic membranous nephropathy and secondary membranous nephropathy.

PURPOSE: This study was to investigate the relation between the number of autophagosomes in podocytes and the syndromes of idiopathic membranous nephropathy (IMN) and secondary membranous nephropathy (sMN). METHODS: The pathological changes in the kidney tissues of patients were detected with the hematoxylin and eosin staining, the periodic acid-Schiff reagent treatment, the Masson's trichrome staining and the immunofluorescence detection (IF). Meanwhile, the autophagosomes in podocyte were analyzed by transmission electron microscopy and the IF assay pointing to LC3-II, an autophagic marker. Clinical data, including age, sex, edema, serum creatinine, estimated glomerular filtration rate, hematuria, urine protein excretion and serum albumin, were collected from in-patient medical records. Finally, the association of podocyte autophagosome numbers with idiopathic membranous nephropathy and secondary membranous nephropathy was studied. RESULTS: Fewer autophagosomes were observed in podocytes of nephropathy group compared with the control group. Moreover, there was a significant difference in the autophagosome number between the two types of MN and each kind of nephropathy demonstrated distinct characteristics. Although the reduced autophagosome number in the IMN cases was not related to sex, this trend was exacerbated along with the progression from pathological stage I to II. In contrast, fewer autophagosomes were observed in class II and V LN patients compared with the controls, while greater numbers were detected in class III and IV LN patients. CONCLUSIONS: The results indicated that the autophagy participated in the podocyte injury in IMN and sMN and the number of autophagosomes in podocytes was related to the pathological classification.