Expression And Clinical Significance Of SIRT1 And POSTN In Serum Of Patients With Diabetic Kidney Disease

Background and objective:Diabetes mellitus（DM）is one of the important public health problems worldwide,and China has now become the country with the largest number of DM patients in the world with increasing incidence of DM year by year.Diabetic kidney disease（DKD）,an important microvascular complication of diabetes mellitus,shows an increasing prevalence.Although active and comprehensive management measures have been taken,the incidence of end stage renal disease（ESRD）caused by DKD has not been reduced.Therefore,it is crucial to investigate the factors associated with progressive diabetic nephropathy and explore effective prevention and treatment measures.Sirtuin-1（SIRT1）and periostin（POSTN）play key roles in the occurrence and progression of DKD.In this study,the serum expression levels of SIRT1 and POSTN in patients with diabetic kidney disease were detected to analyze the relationship between these two proteins and disease progression,explore their clinical value,and evaluate whether SIRT1 and POSTN can be used as new biological markers in the progression of DKD,so as to provide new ideas and experimental basis for the diagnosis and treatment of DKD.Methods:According to the inclusion and exclusion criteria,123 patients with T2 DM or DKD who were admitted to the Department of Nephrology and Endocrinology and Metabolism of Lanzhou University Second Hospital from January 2021 to December2021 were selected,and 35 healthy subjects were randomly selected as the normal control group.According to eGFR and urinary protein levels,they were divided into different risk groups for DKD progression,including the low risk group（L group,n=36）,medium risk group（M group,n=28）,high risk group（H group,n=26）,and extremely high risk group（EH group,n=33）.Demographic data（such as age,gender,BMI,and blood pressure）and clinical data（such as the duration of T2 DM,FBG,HbA1c%,BUN,Scr,eGFR,SUA,TC,TG,HDL-C,LDL-C,ALB,24 h UTP,UAER,and UACR）were collected from all the study subjects.Fasting venous blood（4m L）was collected from the subjects and used to determine SIRT1 and POSTN expression levels in serum by ELISA.The general data,clinical data,and the expressions levels of SIRT1 and POSTN in serum of each group were compared.The correlation between SIRT1 and POSTN expression levels and clinical indicators was analyzed using the Spearman correlation analysis.Multivariate ordered Logistic regression analysis was used to explore the independent influencing risk factors for disease progression in patients with diabetic kidney disease,and ROC curves were drawn to evaluate the diagnostic values of SIRT1 and POSTN in DKD progression.Results:1.Demographic information and clinical data between the normal control group and each DKD risk group were compared,and the results showed that there were no significant differences between different groups in age,HbA1 c,TC,and LDL-C（P>0.05）,while significant differences were found in BMI,blood pressure,duration of T2 DM,FBG,BUN,Scr,eGFR,SUA,TG,HDL-C,ALB,24 h UTP,UAER,and UACR（P<0.05）.Following with an increased risk of disease progression in the patient group,the ALB showed a decreasing trend while Scr,SUA,24 h UTP,UAER,and UACR showed an increasing trend.2.Serum SIRT1 levels were significantly lower and POSTN expression levels were significantly higher in the risk groups compared with the normal control group,and SIRT1 expression levels gradually decreased and POSTN expression levels gradually increased in the M,H,and EH groups as the risk of disease progression increased.3.Spearman correlation analysis showed that SIRT1 was significantly negatively correlated with BMI,SBP,DBP,duration of T2 DM,FBG,BUN,Scr,SUA,TG,24 h UTP,and UACR（P<0.01）,and was significantly positively correlated with gender,eGFR,and ALB（P<0.01）.POSTN expression level was significantly negatively correlated with eGFR,ALB（P<0.01）,and positively correlated with SBP,DBP,duration of T2 DM,FBG,BUN,Scr,SUA,TG,24 h UTP,and UACR（P<0.01）.4.Multivariate ordered Logistic regression analysis showed that Scr（OR=1.036,95%CI: 1.019-1.052,P<0.001）and POSTN（OR=1.019,95%CI: 1.003-1.035,P<0.05）were associated with increased risk of DKD progression,while albumin（OR=0.937,95%CI: 0.884 to 0.994,P<0.05）was a protective factor for disease progression.5.ROC curve analysis of the risk of disease progression by SIRT1 and POSTN showed that SIRT1 predicted the risk of disease progression with an AUC of 0.7213（0.6327-0.8098）,a sensitivity of 67.8%,a specificity of 67.2%,and an optimal truncation value of ≤5.322.POSTN predicted the risk of disease with an AUC of0.8027（0.7252-0.8802）,a sensitivity of 69.5%,a specificity of 79.7%,and an optimal truncation value of >93.289.It indicated that SIRT1 and POSTN were potential predictors for the risk of DKD disease progression.Conclusions:The serum expression level of SIRT1 DKD patients gradually decreased with increased risk of DKD progression,and the expression level of POSTN gradually increased with increased risk of DKD progression.SIRT1 and POSTN can be used as predictors of the risk of DKD disease progression.POSTN is an independent risk factor for increased risk of disease progression.Compared with SIRT1,POSTN has higher sensitivity and specificity in identifying DKD progression.