Effects Of Dapagliflozin On Renal Function And RAAS In Elderly Patients With Early Diabetic Nephropathy

Objective:This study explored the effects of sodium-glucoseco-transporter2(SGLT2)inhibitors on renal function,renin-angiotensin-aldosterone system(RAAS)and risk factors of microalbuminuria in elderly patients with early diabetic nephropathy,and provided practical support and theoretical basis for the prevention and treatment of early diabetic kidney disease(DKD)in elderly patients.Methods:A total of 97 cases of elderly patients with type 2 diabetes whose urinary albumin-to-creatinine ratio(UACR)≤ 300 mg/g were recruited from the Affiliated Hospital of Qingdao University from September 1,2019 to August 1,2021,adopting the method of hierarchical randomization.According to UACR,there were 47 cases in the normal UACR group(UACR < 30 mg/g)and 50 cases in the early DKD group(30 mg/g≤UACR≤300 mg/g).The early DKD group still needed to meet the diagnostic criteria for early DKD.Then they were randomly divided into dapagliflozin group(49 cases)and control group(48 cases).Height,weight,Body Mass Index(BMI),blood pressure,urinary microalbumin,UACR,cystatin C,urea nitrogen,creatinine,glomerular filtration rate(e GFR,EGFR)were collected.Estimated Glomerular Filtration Rate,uric acid,fasting blood glucose,fasting Insulin,fasting C-peptide and Homeostasis model Assessment-insulin Resistance index(Homeostasis model assessment).HOMA-IR,Homeostasis model assessment-islet beta cell function index,HOMA-β),glycosylated hemoglobin,triglyceride,total cholesterol,High-density lipoprotein cholesterol(HDL-C),HDL-C,Low-density lipoprotein cholesterol(LDL-C),orthotropic renin,orthotropic aldosterone,aldosterone to renin ratio(ARR)and other indexes.The changes of each index before and after 1 year of treatment were compared.According to UACR,dapagliflozin and control group were divided into four subgroups: UACR dapagliflozin normal group,UACR normal control group,early DKD dapagliflozin group,and dapagliflozin early DKD control group.Subgroup analysis was performed.Spearman correlation analysis was used to analyze the relationship between microalbuminuria and other variables in baseline data.Multivariate binary Logistic regression analysis was used to analyze the independent risk factors of microalbuminuria.P < 0.05 was considered statistically significant.Results:1.There were no significant differences regarding gender,age,medication frequency,height,weight,blood pressure,blood lipids,renal function,blood glucose,renin,aldosterone and other related indicators between dapagliflozin and control groups(P > 0.05).During the treatment,there were 3 patients with mild urinary tract infection,and the treatment was not interrupted.2.After 1 year of dapagliflozin group,UACR,urinary microalbumin,creatinine,body weight,BMI,systolic blood pressure,triglyceride,fasting blood glucose,insulin,HOMA-IR,HOMA-β and glycosylated hemoglobin were lower than those before treatment,and e GFR and HOMA-β were higher than those before treatment,and the differences were statistically significant(P < 0.05).After 1 year of treatment,e GFR,triglyceride,fasting blood glucose and HOMA-IR in the control group were lower than those before treatment,while creatinine and HOMA-β were higher than those before treatment,and the differences were statistically significant(P < 0.05).After 1 year of treatment,there were significant differences in UACR,urinary microalbumin,creatinine,e GFR,systolic blood pressure and C-peptide between the two groups(P < 0.05).3.There were no significant changes in the ratio of orthostatic renin,aldosterone and ARR between dapagliflozin group and control group after 1 year of treatment(P > 0.05).4.The body weight,BMI,systolic blood pressure,urinary microalbumin,UACR,urea nitrogen,fasting blood glucose,insulin,HOMA-IR and glycosylated hemoglobin in early DKD dapagliflozin group after 1 year of treatment were lower than those before treatment,and HOMA-β was higher than those before treatment(P < 0.05).After 1 year of treatment,UACR,urinary microalbumin,urea nitrogen,creatinine,e GFR,fasting blood glucose,insulin,HOMA-IR and glycosylated hemoglobin in the early DKD control group were lower than those before treatment,and HOMA-β was higher than those before treatment(P < 0.05).There were significant differences in body weight,BMI,systolic blood pressure,UACR,urinary microalbumin,creatinine,e GFR and C-peptide before and after treatment(P < 0.05).There were no significant changes in renin,aldosterone and ARR before and after treatment(P > 0.05).5.The association between microalbuminuria and other indicators was investigated based on the baseline data of the patients.Microalbuminuria was positively correlated with body weight,systolic blood pressure,diastolic blood pressure,UACR,uric acid,fasting blood glucose,glycosylated hemoglobin,triglyceride,total cholesterol and orthostatic aldosterone(r=0.247,P= 0.015;r=0.327,P =0.001;r=0.287,P =0.004;r=0.894,P < 0.001;r = 0.203,P = 0.046;r=0.406,P < 0.001;r=0.284,P =0.005;r=0.415,P < 0.001;r =0.416,P < 0.001;r =0.387,P < 0.001)microalbuminuria was negatively correlated with e GFR,HOMA-β and HDL-C(r =-0.232,P =0.023;r = 0.296,P = 0.003;r =-0.325,P =0.001).6.Statistically significant indicators(body weight,systolic blood pressure,diastolic blood pressure,e GFR,uric acid,glycosylated hemoglobin,fasting blood glucose,triglyceride,total cholesterol,HDL-C,and aldosterone)were used as independent variables,and microalbuminuria was used as dependent variable for multivariate binary Logistic regression analysis.Body weight and triglyceride were independent risk factors for microalbuminuria(OR 1.086,P =0.020 < 0.05;OR 2.696,P =0.034 < 0.05).Conclusion:1.Dapagliflozin can reduce urinary protein and delay e GFR decline in elderly patients with diabetes and early DKD,thereby protecting renal function in elderly patients with early DKD and T2 DM.2.Dapagliflozin can protect renal function in elderly patients with early DKD and T2 DM by reducing blood pressure.3.Dapagliflozin had no significant effect on plasma renin and aldosterone,and had no significant effect on systemic RAAS.4.Body weight and triglyceride are independent risk factors for microalbuminuria.