Relevance Study Of Serum ATF3 And Proteinuria In Diabetic Kidney Disease Patients

Objective:This study aimed to identify the potential biomarkers for early diabetic kidney disease(DKD)by analyzing the change of serum activating transcription factor 3(ATF3)concentration and its correlation with albuminuria in DKD patients.Methods:Firstly,we screened gene data sets from Gene Expression Omnibus(GEO)database based on inclusion and exclusion criteria.Then we performed the differential gene analysis and weighted gene co-expression network analysis(WGCNA).Finally,the related genes of DKD were obtained by intersecting the above two results.The top 5 key genes were screened according to Degree algorithm in Cytoscape software.Then,we selected patients who were clearly diagnosed as DKD in nephrology department of our hospital from December 2020 to November 2021.According to inclusion and exclusion criteria,we selected DKD patients who met the criteria for analysis.Firstly,they were splited into normal albuminuria group(UACR<30mg/g),trace albuminuria group(UACR30-300mg/g),and massive albuminuria group(UACR>300mg/g)according to urinary albumin/creatinine(UACR).We collected their general information and biochemical parameters.Then we measured the serum ATF3 concentration by enzyme linked immunosorbent assay(ELISA).Finally we performed ANOVA or non-parametric tests to compare the differences in general data and clinical indicators among the three groups.The correlation of serum ATF3 and clinical indicators was analyzed by Pearson or Spearman.Finally,we defined the influencing factors of serum ATF3 by multiple linear stepwise regression.Results:1.The GSE142153 data set was selected,and 48 genes associated with DKD were obtained after intersecting differential genes and WGCNA.The first 5 key genes were obtained after further screening,which were IL10,IL1 A,ATF3,CCL2 and CXCR3.2.A total of 88 DKD patients were included,including 26 cases in the normoal albuminuria group,30 in the trace albuminuria group and 32 in the massive albuminuria group.There were no significant differences in age,sex ratio and BMI among the three groups.Compared with normoal albuminuria group,Hb and ALB were significantly decreased in massive albuminuria group and massive albuminuria group(P <0.05);Scr,BUN,UACR and 24-hour urine protein were significantly higher,and the differences were statistically significant(P <0.05).3.Compared with normal albuminuria group,serum ATF3 was significantly increased in the other two groups,with the highest in the massive albuminuria group.The difference was statistically significant(P <0.05).4.It was found that serum ATF3 was negatively correlated with Hb,ALB and GFR(r =-0.525,-0.751,-0.406,P <0.05).However,it was positively correlated with BUN,Scr,UACR and 24-hour urine protein(r = 0.497,0.426,0.992,0.946,P <0.05).5.Further multiple linear stepwise regression analysis of the above significant indexes with serum ATF3 revealed that Hb,UACR and 24-hour urine protein were the influencing factors of ATF3,and 24-hour urine protein had a greater effect on ATF3.Conclusion:Serum ATF3 concentration was significantly increased in DKD patients,which was positively correlated with the severity of proteinuria.It is expected to be a potential clinical indicator for early monitoring of DKD.