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ObjectiveThis study aims to investigate the role of suPAR in the pathogenesis of podocyte injury in FSGS. Methods① The sera of primary FSGS patients （17 cases） were collected. Healthy volunteers （10 cases） and patients with other types of primary nephrotic syndrome （10 cases） were set as normal and disease controls. SuPAR levels were detected by ELISA； ② Podocytes were stimulated by suPAR in vitro， and cells were collected to analyze apoptosis by flow cytometry and for RNAseq analysis； ③ Differentially expressed genes （DEGs） were screened from RNAseq data. Both up-regulated and down-regulated genes were analyzed by KEGG and GO enrichment analysis. Heat map was used to show expression of genes related to podocyte focal adhesion， slit diaphragm and actin dynamics and endocytosis. Differentially expressed genes were verified by qPCR. Results① The level of suPAR in FSGS patients was significantly increased， and that in other nephrotic syndrome（NS） patients was also significantly increased； ② suPAR stimulation significantly altered the transcriptome pattern of human podocytes. A total of 272 up-regulated genes and 288 down-regulated genes were screened； ③ KEGG and GO enrichment analysis of up-regulated and down-regulated genes showed that Focal adhesion and DNA replication and DNA repair related pathways were significantly down-regulated； ④ suPAR did not increase podocyte apoptosis. ConclusionThe level of suPAR is significantly increased in patients with primary FSGS. SuPAR may promote podocyte injury by interfering with genomic homeostasis and disrupting focal adhesion， slit diaphragm， actin dynamics and endocytosis-related functional molecules of podocytes.
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Objective To investigate the characteristics of infecting pathogens,their changes and antimicrobial susceptibilities on CAPD related peritonitis in our peritoneal dialysis(PD) center in the past 15 years.Methods Two hundred and six CAPD related peritonitis episodes in 145 patients from 2000 to 2005 were analyzed and compared with 109 episodes from 1991 to 2000.The causative pathogens,their antimicrobial susceptibilities and outcomes on CAPD related peritonitis from the two periods were retrospectively reviewed and compared.Results Culture negative rate decreased from 60.6% in 1990 s to 47.6% in the last five years (P=0.031 ).Among culture positive peritonitis episodes,the incidence of gram positive bacteria (GPB) peritonitis increased from 25.6% to 39.8% (P=0.059).This was mainly due to a significant increase in coagulase-neagative staphylococcus peritonitis,which significantly increased from 4.7% to 26.9% (P=0.01).Gram negative bacteria (GNB) peritonitis decreased slightly (44.2% vs 34.3%,P=0.322).The incidence of Klebsiella pneumoniae peritonitis significantly decreased (14.0% vs 3.7%,P=0.023),while Pseudomonas aeruginosa and Escherichis coli peritonitis rates slightly increased (4.7% vs 9.3%,P = 0.338;7% vs 18.7%,P=0.072).The decrease of fungal peritonitis rate was not significant (30.2% vs 17.6%,P= 0.123).The comparison of clinical outcomes showed an improvement of total recovery rate from 68.8% in 1990 s to 73.9% for 2000-2005 (P=0.09).The catheter removal rate decreased from 19.2% to 14.3% (P=0.238),and the mortality from 10.1% to 5.4% (P=0.118).In both periods,fungal peritonitis had the poorest results,which all the patients either withdrew from PD or died.Conclusions Compared with that in 1990 s,the culture positive rate for CAPD related peritonitis in 2000-2005 has been greatly improved.Coagulase-negative staphylococcus is the most common causative pathogen.The mortality and catheter removal rate have been markedly reduced in the last five years.Fungal peritonitis is the most important reason for patients' dropout.