| Objective:Retrospectively analyzed the clinical and pathological characteristics of patients with idiopathic membranous nephropathy(IMN)in Xinjiang and explored the risk factors for the decline of glomerular filtration rate(eGFR).Compare the urine proteome of IMN patients with renal tubular interstitial fibrosis(TIF)and IMN patients without TIF,study the differential protein profiles of urine in IMN renal fibrosis in Xinjiang,and use protein database for search and analysis to compare the differential expression Urine protein,to explore the pathogenesis of renal fibrosis in IMN patients,preliminary screening of candidate biomarkers for IMN renal fibrosis in Xinjiang.Methods:(1)119 patients who were diagnosed as IMN in our hospital from January 2017to December 2018 were included,and the patients were divided into normal eGFR groups according to the estimated glomerular filtration rate[eGFR?90mlˇmin1ˇ(1.73m~2)]58patients and eGFR decreased group[eGFR<90mLˇmin1ˇ(1.73m~2)]61 cases,compared the clinical indicators and pathological data differences between the two groups of patients,using Logistic regression equation to analyze the risk factors affecting renal function decline in IMN patients.(2)In this study,the urine of patients with IMN nephropathy diagnosed by renal biopsy in Xinjiang was used as the research object.Urine samples of patients with IMN and TIF(n=12)and patients with IMN and TIF(n=12)were extracted by acetone precipitation Proteins in the urine,combined with albumin/IgG antibodies to remove high-abundance proteins,urine using isotope relative labeling and absolute quantification(iTRAQ)labeling two-dimensional liquid chromatography and tandem mass spectrometry(LC-MS/MS)technology Proteomics detection method,performing differential urine proteomics analysis on the pathological manifestations of IMN nephropathy,obtaining urine differentially expressed proteins,performing gene ontology(GO)analysis and signal pathway enrichment on the identified proteins and differential proteins,according to the possibility of IMN renal fibrosis Pathogenesis and enrichment of differential proteins,four urine differential proteins were initially screened and could be used as candidate biomarkers for urine related to renal fibrosis in IMN patients in Xinjiang.Results:(1)In terms of clinical data,the age,proportion of hypertensive patients,blood creatinine,and urea nitrogen of patients with decreased eGFR were significantly higher than those with normal eGFR(P<0.05),and serum albumin and total serum protein levels were significantly lower than with normal eGFR Group(P<0.05);in terms of renal pathology,the proportion of glomerular sclerosis,renal tubule atrophy,renal interstitial fibrosis,interstitial inflammatory cell infiltration,and thickening of small arteries in patients with eGFR decreased was significantly higher than that of normal eGFR Group(P<0.05).Logistic regression analysis showed that advanced age and renal interstitial inflammatory cell infiltration were independent risk factors for eGFR decline in IMN patients,and high serum albumin levels were protective factors for eGFR decline in IMN patients(2)Through liquid-mass spectrometry analysis,a total of 192 urine proteins were found to be significantly different between IMN patients with TIF and those without TIF.Among them,39 urine proteins were up-regulated in the IMN combined TIF group,and 153 urine proteins were down-regulated in the IMN combined TIF.GO analysis and signal pathway enrichment revealed that the peroxisome proliferator-activated receptor(PPAR)pathway,phosphatidylinositol 3'-kinase(PI3K)-Akt signaling pathway and cell matrix adhesion pathway are in the renal tubules of IMN Interstitial fibrosis plays an important role in the occurrence and development of the process.The protein interaction network analysis findings are consistent with the above pathways.Further screening of differential urine proteins found that APOA1,LRG1,LCN2,CD248 may be a diagnosis of IMN kidney Candidate noninvasive biomarkers for fibrosis can be used as candidate proteins for further functional verification and analysis.Conclusions:In a single-center,retrospective study of idiopathic membranous nephropathy,we found that TIF is one of the pathological changes of IMN.Compared with the normal IMN renal function group,the proportion of renal fibrosis in the IMN decreased renal function group was more and more severe,and renal interstitial fibrosis is related to the progression of IMN.Therefore,there is an urgent need to find non-invasive biological indicators that can replace invasive kidney biopsies to determine the degree of renal fibrosis of IMN earlier,and find targeted drugs to inhibit,reverse or even eliminate renal fibrosis,in order to protect renal function and delay the occurrence of ESRD.The differential urine protein expression profile found that PPAR signaling pathway,Pl3K-Akt signaling pathway and cell matrix adhesion pathway play an important role in the occurrence and development of renal fibrosis in IMN,APOA1,LRG1,LCN2,CD248 may be It is a candidate noninvasive biomarker for diagnosis of IMN renal fibrosis. |
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