Prevalence Of Chronic Kidney Disease And Related Phenotypes And Genotypes In Adults Of Pudong New Area Of Shanghai

Objective:To investigate the prevalence of chronic kidney disease (CKD) and its associations with metabolic factors and metabolic syndrome (MS), and to evaluate the association of CKD specific phenotypes with the genetic polylmorphisms of Angiotensin Ⅱ type Ⅰ receptor (AT1R), Angiotensinogen (AGT), Paraoxonase-1(PON1) in adults of Pudong New Area of Shanghai, China.Method:In this cross-sectional study conducted during the period of April-July2008,5927adults aged20-80years were randomly selected from Pudong New Area of Shanghai through multistage sampling. After obtaining written consent, a structured in-person interview was conducted by trained personnel to collect information on demographic factors, prior history of chronic diseases, diet, cigarette and alcohol use, physical activity and use of medications. At the interview, each participatant was measured standing height, body weight, waist and hip circumferences and blood pressure according to a standardized protocol. A10mL fasting blood sample and a morning ovid urine sample were collected from each participant and were used to measure fasting plasma glucose (FPG), serum levels of triglycerides (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), and creatinine(SCr), as well as urinary concentrations of creatinine and albumin. Urine albumin to creatinine ratio (ACR) and glomerular filtration rate (GFR) were calculated using both the Modification of Diet in Renal Disease (MDRD) equation (modified for Chinese adults) and the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. CKD was defined as either decreased kidney function (eGFR<60mL-min-1·(1.73m2)-1) or kidney damage (ACR>30mg/g). After excluding subjects having ever taken antihypertensive, anti-glycemic, or antilipemic medications,2,026participants were randomly selected to genotype the single nucleotide polymorphisms (SNPs) at AT1RA1166C, AGT rs699and PON1rs662by using polymerase chain reaction-ligase detection reaction (PCR-LDR) method. All data analyses were conducted using PASW Statistics18.0. Demographic and clinical characteristics between or among subgroups were compared using χ2test for categorical variables, and t-test, ANOVA test, Kolmogorov-Smirnov(KS) test or Kruskal-Wallis (KW) test for continuous variables. P for trend was obtained using generalized linear model (GLM). Logistic regression model was used to estimate the odds ratio (OR) and95%confidence interval (95%Cl) for the demographic and risk factors with the indicators of kidney damage. P value<0.05was considered statistically significant. Age-adjusted prevalence was calculated with the direct method according to world population for standardization.Results:Of5584adults participating in the study with the completement of the questionnaire, the average age was50.4±14.1years old and44.4%were male. The overall prevalence of albuminuria, microalbuminuria and macroalbuminuria were10.9%,11.9%and0.9%, and decreased to9.3%,9.9%and0.6%, respectively, after adjusting for age. By using the MDRD Study equation, the crude prevalence of decreased kidney function was1.5%(the age standardized prevalence was1.1%), with1.9%for men and1.1%for women (the age standardized prevalence was1.3%and0.9%). The crude prevalence of CKD was12.6%(the age standardized prevalence was11.0%), with10.6%for men and14.2%for women (the age standardized prevalence was8.8%and12.7%). Both hypertension and dysglycemia were strong independent predictors of CKD. The prevalence of CKD increased significantly across the healthy subjects (5.1%for men,9.7%for women), subjects only with dysglycemia (11.8%for men,15.5%for women), subjects only having hypertension (12.5%for men,16.8%for women), and subjects with both hypertension and dysglycemia (19.4%for men,23.5%for women). Among the normotensive, prehypertensive, undiagnosed hypertensive and diagnosed hypertensive subjects, the prevalence of CKD was6.7%,10.6%,18.1%and21.3%, respectively. Both prehypertension and hypertension were associated with prevalence of albuminuria and CKD, with respective OR of1.52(95%CI:1.16-1.99) and2.31(95%CI:1.74-3.05) for albuminuria, and1.34(95%CI:1.03-1.74) and2.05(95%CI:1.57-2.68) for CKD.The level of ACR was observed to increase with increasing levels of blood pressures, while the blood pressure was also observed to increase with increasing levels of albuminuria. The association appeared independent of eGFR level. The prevalence of CKD was9.2%,14.1%,28.5%and30.9%, respectively, among those with normoglycemia, prediabetes, undiagnosed diabetes and diagnosed diabetes. The prevalence of CKD and the average levels of age, BMI, SBP, DBR MAP and ACR. were observed to increase with increasing quartiles of TG, TC and LDL-C, but decreased with increasing quartiles of HDLC. The levels of eGFR, conversely, decreased along with the quartiles of TG, TC and LDL-C. The prevalence of albuminuria, decreased kidney function and CKD was independently associated with overweight or obesity, and increased with increasing quartiles of BMI, WC, WHR and WHtR. As a result, the prevalence of microalbuminuria, macroalbuminuria, decreased kidney function and CKD were higher in subjects with MS than those without. MS remained an independent risk factor for CKD. Among the components of MS, dysglycemia was the strongest one related with albuminuria and CKD, with adjusted OR being2.40(95%CI:1.99-2.89) and2.24(95%CI:1.86-2.68), respectively. Hypertension was the only one associated with decreased kidney function. The risk of CKD increased with increasing number of MS components. Compared with subjects with1component, adjusted OR for CKD in subjects with all four components was5.62(95%CI:3.96-7.97). Among the subjects having never taken antihypertensive, anti-glycemic, or antilipemic medications, the average levels of urinary albumin, ACR and the prevalence of decreased kidney function differed by genotypes at PON1rs662. A allele at PON1-rs662is related with lower level of ACR in males and lower levers of urinary albumin, ACR, and BMI in females, and was significantly associated with decreasd risk of albuminuria and renal insufficiency, with OR being0.78(95%CI:0.61-0.99) and0.45(95%CI:0.23-0.89), respectively. T allele at AGT-rs699is related with lower level of SBP, DBP and MAP in males. No significant association was observed for genotypes at AT1R Al166C with any CKD-related phenotypes. The prevalence of CKD calculated using the CKD-EPI equation was slightly higher than that calculated using the MDRD Study equation. However, the association patterens of CKD with MS, components of MS and genotype of PON1rs662, AT1R A1166C and AGT rs699did not change substantially.Conclusions:The prevalence of CKD, albuminuria and decreased kidney function in Pudong New Area of Shanghai are even higher than those in other countries and in other areas of China. CKD is strongly associated with MS and its components. PON1rs662A allele is linked to average levels of urinary albumin, ACR, BMI, and the prevalence of decreased kidney function. Our results suggest that CKD is becoming a public health problem in the area. Screening programme and a community-integrated control strategy should be conducted in the population. Further multidisciplinary studies including molecular epidemiology are warranted to provide more evidences on environmental and genetic risk factors of CKD.