The Correlation Between Serum Bisphenola Leveland The Progression Of Type 2 Diabetic Nephropathyand Hypertensive Nephropathy

PART I THE CORRELATION BETWEEN SERUM BISPHENOL A LEVEL AND THE DEVELOPMENT OF TYPE 2 DIABETES AND DIABETIC NEPHROPATHYObjective: To evaluate whether serum bisphenol A(BPA) could predict the progression of type 2 diabetes mellitus(T2DM) and the diabetic nephropathy in cohort study.Methods: Our research divided to two groups. Group one used prospective cohort to explore the relationship between serum BPA and the progression of T2 DM. Group two used prospective observational cohort to study the relationship between serum bisphenol A and the progression of type 2 diabetic nephropathy. In group one, we recruited 3349 volunteer which are free of diabetes from 2008. Medical history, age, sex, body mass index(BMI), blood pressure(BP) and other clinical characteristics were collected. Biochemical markers, such as serum lipid, blood glucose, hepaticfunction, renal function were measured. ELISA was used to measure serum BPA concentration. Followed up for 6 years, a total of 145 man and 85 women developed T2 DM. Controls which didn’t develop T2 DM were randomly selected in a 1:1 ratio from the same cohort to match age and gender. Regression models were used to analyze the associations of serum BPA with the risk of T2 DM development.In group two, we recruited 166 volunteer with diabetes in 2008.Detail medical history and complication of T2 DM enquiry were processed.Serum creatinine and cystatin C were determined to calculate the estimated glomerular filtration rate(e GFR), excluding 45 sample which e GFR <60ml/min/1.73m2. ELISA was used to measure the rest of 121 sample serum BPA concentration. Other data was collected as same as group one.The chronic kidney disease(CKD) was divided into 5 stage. Development of CKD was diagnosed with e GFR < 60 m L/min/1.73m2 at the last follow-up. Correlation analysis and regression models were used to analyze the associations of serum BPA with the risk of type 2 diabetic nephropathy development.Results: In group one the body mass index(BMI),systolic blood pressure(SBP), diastolic blood pressure(DBP), fasting plasma glucose(FPG), 2 hours plasma glucose(2h PG), total cholesterol(TC),triglycerides(TG), low density lipoprotein cholesterol(LDL-c) of T2 D were significantly higher than controls at baseline, P<0.05.There was nosignificant difference of serum BPA between T2 DM subjects and controls[1.3(0.3, 3.7) vs 1.6(0.4, 3.9)(ng/m L), P=0.199] at baseline. After being matched for various factors, serum BPA concentration cannot predict T2 DM development independently [(OR) 0.93(95 % CI 0.41, 2.13),P=0.869].In group two, baseline serum BPA concentration was0.40(0.17,1.40)ng/m L. Duration 6 years of T2 DM, baseline waist circumference(WC), SBP, DBP, FPG, and serum BPA level were significantly negatively associated with the annual change and percentage change in e GFR. After adjusting for age, sex and BMI, baseline serum BPA level had a significant negative association with the annual change in e GFR(β=-0.371, P<0.001) and percentage change in e GFR(β=-0.391, P<0.001). All subjects were divided into three subgroups according to serum BPA concentrations at baseline. Multivariate logistic regression analysis showed that patients with high levels of serum BPA exhibited about a sevenfold increased risk of developing CKD compared to patients with low levels of serum BPA [odds ratio(OR) 6.65(95 % CI 1.47, 30.04),P=0.014].Conclusion: Serum BPA can not predict T2 DM independently but may be a predictor of CKD in patients with T2 DM.PART II THE CORRELATION BETWEEN SERUM BISPHENOL LEVELAND THE PROGRESSION OF HYPERTENSIVE NEPHROPATHYObjective: Hypertensive nephropathy is one of the major causes of chronic kidney disease(CKD). Bisphenol A(BPA) is associated with elevated blood pressure and urinary albuminuria. The aim of this study is to evaluate the association between serum BPA and the progression of CKD in patients with primary hypertension.Methods: In this 6 years prospective study, we recruited 302 volunteer suffering from hypertension with e GFR ≥ 60ml/min/1.73m2.Medical history, age, sex, BMI, blood pressure and other clinical characteristics were collected. Biochemical markers, such as serum lipid,blood glucose, hepatic function and renal function were measured. ELISA was used to measured serum BPA concentration. Serum creatinine and cystatin C were determined to calculate the estimated glomerular filtration rate(e GFR). The development of CKD3(e GFR<60ml/min/1.73m2) was defined as hypertensive nephropathy. Correlation analysis and regression models were used to analyze the associations of serum BPA with the risk ofhypertensive nephropathy development.Result: Totally 46 patients developed CKD stage 3 or greater after a six-year follow-up. Baseline serum BPA concentration was0.61(0.26,2.44)ng/ml which was significantly negatively correlated with the annual change in e GFR(R=-0.197, P<0.001). After adjusting for age,BMI, serum creatinine and cystatin C,baseline serum BPA level had a significant negative association with the annual change in e GFR(β=-0.132,P=0.007). Univariate logistic regression analysis showed that the baseline age, SBP, e GFR and serum BPA levels were predictors of CKD stage 3 or greater. All subjects were divided into three subgroups according to serum BPA concentration at baseline. In multivariate logistic regression analysis,patients with high serum BPA levels exhibited significant increased risk of developing CKD stage 3 or greater compared with patients with low serum BPA levels [OR 4.79(95% CI 1.81, 14.25), P=0.004].Conclusion: Serum BPA may be a predictor of hypertensive nephropathy progression in patients with primary hypertension.