A Study On Primary Nephrotic Syndrome By Metabolomics

Objective:Nephrotic syndrome (NS) is a common kidney disease,which can be divided intoprimary and secondary NS. The primary NS include five pathologic type, and thepathological diagnosis for the primary NS is very important to its effective treatmentand prognosis judgment, and it often completed through renal biopsy.However,renalbiopsy can cause some complications, including bleeding, arteriovenous fistula,andsomeother complications,and there may be life-threatening bleeding occurs. Thus,finding specific blood biomarkers in different pathological type of primary NS hasvery important significance. The purpose of this study is to find the differences insubstance from various types of primary NS patients and reveal the correlationbetween these substances and pathological type, by using liquid chromatography/mass spectro-metry technology in metabolomics. In the conditions that the patientscan not be preformed renal biopsy,the biomarkers can help us to make diagnosis anddifferential diagnosis of primary NS pathological type,and reduce trauma,contribute toits therapeutic,and may be expected to explore the basis for the pathogenesis ofprimary NS. This research provide novel studies on searching the biomarkers ofpathological type of primary NS.Methods:1.Subject investigated and brigade laboratory:In this study,32nephroticsyndrome patients were selected which were received treatment in our hospital.Theserum were collected from the patients.As the research object,the patients weredivided into four groups according to their renal biopsy pathology.For group1,group2,group3,group4,there are eight cases in each group and thirty-two cases in group5.Group1is IgA nephropathy.Group2is Mesangial proliferative glomerulonephritis.Group3is Membranous nephropathy.Group4is Minimal change glomerulopathy.Group5is normal control which is the healthy subjects.2. Plasma liquid chromatography-tandem mass spectrometry(LC/MS): Afterpretreatment, the samples were subjected to HPLC separation, then the data wereanalysed by the EMS or Q1Mass full scan analysis, all of the compounds can be detected by mass spectrometry data.3.Screening and identification of candidate biomarkers:After mass spectrometrydata conversion,take principal component analysis (PCA) and partial least squaresdiscriminant analysis (PLS-DA) for example,we usually use statistical analysis ofthe information contained in ion,in order to look for content or types of ion duringprimary nephrotic syndrome patients with the blood of healthy people.Finally wesearch for the information of candidate biomarkers through retrieve metabolomicsdatabase,to be fixed the preliminary determination of the candidate biomarkers.Results:1.In this study,we analysed human plasma metabolic profiling by LC/MS.Wealso demonstrated the differences between the metabolites in the nephrotic syndromepatients and nomal through multidimensional statistical methods.2. In this study,after preliminary screening,we detected4896ions and12potential bio-markers.They are CoQ-10, N-Methylputrescine, L-alpha-glutamyl-L-hydroxyproline, Gangli-oside GM2(d18:0/16:0), SM(d18:1/18:1(11Z)), N-Octanoyl-Glycine, Aspartyl-Tyrosine, Alpha-CEHC, Creatinine, Ethanolamine, Methionyl-Cysteine, LysoPC (20:5(5Z,8Z,11Z,14Z,17Z)).Conclusion:Metabolomics studies provide new potential biomarkers for the diagnosis ofpathological types of nephrotic syndrome individualized treatment.