We aimed to analyze the changes in plasma leptin, serum inflammatory factors and urinary protein in children with nephrotic syndrome before and after treatment and their clinical significance. A total of 28 children treated and diagnosed with nephrotic syndrome between November 2015 and October 2016 were selected as treatment group, while 25 healthy children were selected as control group. There were no statistically significant differences in age, sex, body mass index (BMI), serum albumin and other general data between treatment group and control group (P>0.05). There was a positive correlation between serum high-sensitivity C-reactive protein (hs-CRP) level and 24 h urinary protein level in children with nephrotic syndrome before treatment (r=0.408, P=0.005). Twenty-four hours urinary protein, urea nitrogen (BUN) and serum creatinine (SCr) levels in children with nephrotic syndrome before treatment were significantly higher than those in normal children, and these indexes were significantly decreased after treatment. The levels of plasma leptin and serum inflammatory factors (hs-CRP and IL-18) in children with nephrotic syndrome before treatment were obviously higher than those in normal children, and these indexes were obviously decreased after treatment. In conclusion, the detection of changes in plasma leptin, serum inflammatory factors (hs-CRP and IL-18) and urinary protein in children with nephrotic syndrome before and after treatment has important reference value for reflecting the severity of disease and evaluating the prognosis of children with nephrotic syndrome.

No abstract

Activation of the purinergic P2X7 receptor (P2X7R) has been associated with the development of experimental nephritis. Therefore, the current study aimed to explore the mechanism of P2X7R in renal injured mice with adriamycin (ADR) nephropathy. The protective effect of a P2X7R antagonist on the kidneys of mice with ADR nephropathy was also evaluated. Nephropathy was induced by a single intravenous injection of ADR (10.5 mg/kg). A total of 6 h before the model was established, the P2X7R antagonist A438079 (100, 200 and 300 µmol/kg) was injected into the mice, which was subsequently administered daily for 1 week by intraperitoneal injection. Subsequently, all mice were sacrificed, after which blood, 24 h-urine and the kidneys were collected. The levels of albumin (ALB) and total cholesterol (TC) in the serum, along with urine protein content at 24 h were determined using an automatic biochemical analyzer. The levels of IL-1β and IL-18 were additionally detected in the renal tissues by ELISA. Moreover, the expression of P2X7R, oxidized (ox)-low density lipoprotein (LDL), C-X-C motif chemokine ligand 16 (CXCL16), Bax, caspase-3 and NLRP3 in renal tissues was detected by immunohistochemistry. Apoptosis in the renal tissues was observed using the TUNEL assay. The results demonstrated that compared with the control group, decreased weight, increased proteinuria, decreased serum ALB and increased serum TC was observed in the ADR group. The expression of IL-1β, IL-18, P2X7R, ox-LDL, CXCL16, Bax, caspase-3 and NLRP3, as well as cellular apoptosis in the renal tissues of the ADR group, was significantly increased in the ADR group compared with the control. However, compared with the ADR group, the changes in all indices in the ADR + A438079 groups were attenuated. Overall, P2X7R, ox-LDL and CXCL16 may be associated with ADR nephropathy, while inhibition of P2X7R may reduce the expression of ox-LDL by downregulating the CXCL16 pathway to alleviate kidney injury in mice with ADR nephropathy. Furthermore, activated P2X7R may promote the release of inflammatory cytokines IL-1β and IL-18 through the downstream P2X7R/NLRP3 pathway and upregulate the expression of Bax and caspase-3 to promote apoptosis, which participates in the process of ADR nephropathy. Inhibiting P2X7R may also reduce the release of IL-1β and IL-18 by downregulating the P2X7R/NLRP3 pathway, downregulating the expression of Bax and caspase-3, and reducing apoptosis, thereby alleviating kidney injury in mice with ADR nephropathy.

This study aims to evaluate the effect of purinergic ligand-gated ion channel 7 receptor (P2X7R) antagonist A438079 in kidneys of children with primary nephrotic syndrome (PNS). In vitro, human podocytes were respectively stimulated with oxLDL (80 µg/ml), A438079 (10 µmol/L), or the compound oxLDL and A438079 together.CXC chemokine ligand 16 (CXCL16) and P2X7R expression levels were detected by Western blot and immunofluorescence assay, respectively. Immunofluorescence assay was used to detect Dil-oxLDL, and a Colorimetric Cholesterol Detection Kit was used for quantitative determination. Our results demonstrated that CXCL16 and P2X7R expression levels were remarkably increased in the renal tissue from children with PNS, particularly in the same location. Furthermore, in contrast to children with minimal change disease, the expressions of P2X7R and CXCL16 in renal tissue of children with focal segmental glomerulosclerosis were more obvious. In vitro, CXCL16 and P2X7R expression levels in human podocytes stimulated with oxLDL were markedly elevated accompanying higher intracellular lipid accumulation compared with the normal control group. In addition, pretreatment of human podocytes with A438079 before the start of oxLDL stimulation causes a significant reduction in CXCL16 expression and a decrease in lipid accumulation. Overall, CXCL16 and P2X7R may participate in the progression of PNS. The lipid accumulation reduction caused by A438079 may be through deregulating the CXCL16 pathway, suggesting that there is a potential role for P2X7R antagonists to remedy PNS.