Correlation Between Urine SerpinA3 And Diabetic Nephropathy

Objective:Serine-peptidase inhibitor clade A member 3(SerpinA3)is a secreted protein associated with inflammation,which high expression is thought to be related with the progression of acute kidney injury and lupus nephritis.However,the urine SerpinA3 level in diabetic nephropathy(DN)is still unclear,and its predictive value for DN is also unknown.The purpose of this study was to investigate the correlation between urine SerpinA3 level and DN,and to explore the potential application value of urine SerpinA3 in the diagnosis of DN.Methods:In this study,105 patients with type 2 diabetes mellitus(T2DM)who were admitted for treatment in Qilu Hospital of Shandong University from August 2021 to October 2022 were selected,and 20 health check-ups from the physical examination center of our hospital during the same period were used as the control group.According to the urine albumin creatinine ratio(UACR),the patients of T2DM were divided into three groups:taking UACR<30mg/g as the node,17 patients were selected as the simple diabetic group;taking 30mg/g≤UACR<300mg/g as the node,20 patients were admitted as the microalbuminuria group;taking UACR≥300mg/g as the node,68 patients were selected as the macroalbuminuria group,the combination of microalbuminuria group and macroalbuminuria group were defined as DN group.Fasting venous blood and clean catch midstream were collected after the informed consent of the patients.The urine and serum SerpinA3 levels were detected by ELISA.The general clinical data and laboratory examination indicators of all subjects who meet the standers were collected,including age,gender,duration of DM,the history rate of hyperlipidemia,hypertension,smoking,systolic blood pressure,diastolic pressure,body mass index(BMI),albumin(Alb),fasting blood glucose(FBG),glycosylated hemoglobin(HbA1c),serum creatinine(Scr),blood urea nitrogen(Bun),estimated glomerular filtration rate(eGFR),uric acid(UA),cystatin C(Cys C),UACR,blood lipid and neutrophil-to-lymphocyte ratio(NLR).SPSS25.0 was used for statistics,and the significance level was all P<0.05.Results:1.Comparison of the general clinical indicators:There were significant differences in age,BMI,the history rate of hypertension,systolic blood pressure and diastolic blood pressure among each group(P<0.05),while there was no significant difference in sex,the history rate of hyperlipidemia and smoking among each group(P>0.05).2.Comparison of laboratory indicators:There were significant differences in NLR,TG,HDL-C,TC,FBG,HbAlc,Alb,Hb,Bun,Scr,UA,Cys C,UACR and eGFR among each group(P<0.05),while there was no significant difference in LDL-C among each group(P>0.05).3.Comparison of urine and serum SerpinA3 levels among each group:The urine SerpinA3 levels in microalbuminuria group[4.75(3.94,5.69)vs 1.46(1.27,2.07)μg/ml,(P=0.008)]and macroalbuminuria group[11.33(8.41,15.88)vs 1.46(1.27,2.07)μg/ml,(P<0.001)]were significant higher than those in control group,while the urine SerpinA3 level in simple diabetic group had no significant difference compared with control group(P>0.05).Further comparison among subgroups of T2DM patients showed the urine SeprinA3 level in macroalbuminuria group was also significantly higher than that in simple diabetic group[11.33(8.41,15.88)vs 3.73(2.74,4.61)μg/ml,(P<0.001)]and microalbuminuria group[11.33(8.41,15.88)vs 4.75(3.94,5.69)μg/ml,(P<0.001)],while the urine SerpinA3 in microalbuminuria group had no significant difference compared with the simple diabetic group(P>0.05).There was also no significant difference of serum SerpinA3 levels among four groups(P=0.736).4.Comparison of urine SerpinA3 levels among different DN progression risk groups:According to different risk of progression,DN patients were divided into low-risk,intermediate-risk,high-risk and extremely high-risk groups.Urine SerpinA3 level showed an increasing trend with the increasing risk of DN progression,which in extremely high-risk group increased more significantly than low-risk group[11.44(9.53,15.90)vs 4.8(3.82,5.48)μg/ml,(P<0.001)].Urine SerpinA3 levels in intermediate-risk and high-risk groups were higher than those in low-risk group,while there was no significant difference of urine SerpinA3 levels among low-risk,intermediate-risk and high-risk groups(P>0.05).5.Correlation analysis of urine SerpinA3 and the following indicators:The urine SerpinA3 was positively correlated with systolic blood pressure(r=0.462),diastolic blood pressure(r=0.233),NLR(r=0.518),UACR(r=0.835),Scr(r=0.593),Bun(r=0.659),UA(r=0.390),Cys C(r=0.620),and BMI(r=0.326),and had significant negative correlation with Alb(r=-0.660),Hb(r=-0.547)and eGFR(r=-0.562),all of which had statistical significance(P<0.05).There was no significant correlation with age,gender,TG,HDL-C,LDL-C,TC,FBG and HbAlc(P>0.05).6.Analysis of influencing factors of urine SeprinA3 level:The urine SerpinA3 level was associated with the risk factors of DN,which of T2DM patients with hypertension was significantly higher than that in T2DM patients without hypertension(P=0.031),while the duration of diabetes,hyperlipidemia and smoking history had no significant effect on urine SeprinA3 level of T2DM patients(P>0.05).The multiple linear regression analysis showed that following multiple adjustments for age,gender,BMI and other indicators,the systolic blood pressure(β=0.227,P=0.045)and UACR(β=0.549,P<0.001)were independent risk factors of urine SeprinA3 level.7.Analysis of influencing factors of DN:The binary logistic regression showed that BMI[OR=1.800,95%CI(1.059,3.059),P=0.030],systolic blood pressure[OR=1.158,95%CI(1.027,1.306),P=0.017]and urine SerpinA3 level[OR=1.439,95%CI(1.014,2.042),P=0,042]were independent risk factors of DN.8.ROC curve analysis of urine SerpinA3 in the diagnosis of DN:Urine SerpinA3 could be used to predict the occurrence of DN.The area under the curve(AUC)of urine SerpinA3 in the diagnosis of DN was 0.9310(PI<0.05).The optimal cut-off value of urine SerpinA3 was 4.524μg/ml,and the sensitivity and specificity were 91.8%and 89.2%,respectively.Conclusion:1.Urine SerpinA3 level was significantly increased in DN patients.2.Urine SerpinA3 was positively correlated with UACR and negatively correlated with eGFR,which could reflect the severity of renal impairment to a certain extent.3.Urine SerpinA3 was an independent risk factor of DN,which had a good predictive value for the occurrence of DN.