Epidemiology Study On The Renal Function In Hypertensive Population Of Rural Communities In North Jiangsu

Prevalence of chronic kidney disease (CKD) is increasing dramaticallyworldwide, which is one of the dominant public health problems to all of humanity inthe21stcentury. CKD will progress into end stage renal disease (ESRD) requiringrenal replacement therapy. This will not only influence life quality of CKD patientsseriously, but also bring heavy economic burden to patients and the society. How toprevent and treat CKD in order to prolong the decline of renal function is becoming aresearch hot point at present。Primary hypertension is the commonest cardiac vascular disease (CVD), andalso one of the most important risk factor for CKD. Hypertension is highly prevalentin China. It is estimated that there are at least200million hypertensives now, two outof every10people. For this reason, figuring out patitents with impared renal functionin hypertensive patients and intervening with the relevant risk factors are meaningfullfor the early prevention of CKD.CVD is the most serious comorbidity and the primary cause of deaths for CKDpatients. In recent years, more and more attention has been paid to homocysteine(Hcy), a new risk factor for atherosclerosis. Increasing evidences demonstrated thatHcy was associated with risks for stroke, coronary heart disease and a number ofother disease statuses such as neural tube defect and also ESRD.Hyperhomocysteinemia in CKD and ESRD patients is generally acknowledged andhas been taken as an important reason for the high CVD morbidity in CKD patients.Significant loss of renal function will inevitably lead to hyperhomocysteinemia,as frequently observed in patients with ESRD. However, plasma level of Hcy is alsonegatively correlated with renal function in general polulation. It is not clear whether hyperhomocysteinemia plays a pathogenic role in decreased renal function in humans,but some researchers found in animal models that hyperhomocysteinemia couldinduce glomerular injury.Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of5,10-methylenetetrahydrofolate to5-methyltetrahydrofolate, a co-substrate forhomocysteine remethylation to methionine. C677T, a single nucleotide polymorphism(C>T) at nucleotide position677, leads to Ala>Val codon substitution at amino acidposition222. MTHFR C677T is a major genetic determinant forhyperhomocysteinemia. However, few have investigated the association betweenC677T and kidney function.From2008, we carried out a clinical research,“China Stroke Primary PreventStudy”, in rural residents, aged45~75years, who lived in the villages in Ganyu andDonghai Counties of Lianyungang District. we examined the renal function, plasmaHcy levels and MTHFR C677T polymorphism, in order to investigate the distributionof renal function in a large population of primary hypertensives in North Jiangsu andfigure out the risk factors for early renal function decline, focusing on the relationshipamong Hcy, MTHFR C677T polymorphism and renal function. We are expecting thatthe data in a large hypertensive population can provide clues for the questions aboveand also providing scientific basis for early prevention of CKD according to thecontrol of associated risk factors.Part1The Distribution and Impact Factors of Renal Function inHypertensive Population of Rural Communities in NorthJiangsuBackground:The incidence of chronic kidney disease (CKD) is increasing worldwide. Hypertension is one of the most important risk factor of CKD. So it is meaningful toinvestigate and figure out the impact factors for early renal function decline inhypertensive patients. Pretreating these risk factors will be very important for theprevention of CKD in hypertensive patients.Objective:To investigate the distribution of renal function in a large hypertensive patients innorth Jiangsu of China and figure the impact factors for early renal function decline ina cross-sectional study.Methods:We analyzed the baseline data of participants of an ongoing China Stroke PrimaryPrevention Trial (CSPPT): a Post-marketing, Double-blind, Randomized ControlledTrial in Lianyungang, Jiangsu province. A total of18,814primary hypertensivepatients (6914males,11900females) were included in the study.Results:The percentage of subjects with CKD (eGFR<60ml/min/1.73m2) was3.3%, whichwere3.1%and3.4%respectively in males and females. According to multiple linearregression analysis, the glomerular filtration rate estimated from serum creatininelevels (eGFR) were positively correlated with age, homocysteine (Hcy), diastolicblood pressure (DBP), fasting blood glucose (FBG) and total cholesterol (TC), andinversely correlated with systolic blood pressure (SBP). When dividing subjects intoCKD and non-CKD, in males, older age and higher Hcy level were associated with ahigher risk for CKD, with (OR=1.10,95%CI:1.07-1.13, P<0.00and OR=1.02,95%CI:1.01-1.03, P=0.00); similarly in females, the ORs were1.07(95%CI:1.05-1.09, P<0.00) and1.06(95%CI:1.04-1.08, P<0.00).Conclusion:The percentage of subjects with CKD (eGFR<60ml/min/1.73m2) in primaryhypertensive patients is3.3%, which is higher than general people in China. Age andHcy level are the most important factors associated with renal function. Part2Molecular Epidemiology Study on the association ofMethylenetetrahydrofolate reductase C677T polymorphismwith Renal Function in Hypertensive Population of RuralCommunities in North JiangsuBackground:Plasma level of total homocysteine (Hcy) is negatively correlated with kidneyfunction in general population. However, the causal mechanism of this correlation ispoorly understood.Objective:The purpose of this study is to investigate the association ofmethylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, which isa major genetic determinant of the plasma tHcy level, with estimated glomerularfiltration rate (eGFR) in Chinese of north Jiangsu.Methods:We analyzed the baseline data of participants of an ongoing China Stroke PrimaryPrevention Trial (CSPPT): a Post-marketing, Double-blind, Randomized ControlledTrial in Lianyungang, Jiangsu province. A total of18814primary hypertensivepatients (6914males,11900females) were included in the study.Results:Association between the eGFR and MTHFR C677T genotype was examined bysex-specific regression analyses. In males, TT genotype was associated with1.37ml/min/1.73m2decrease in eGFR (p=0.004) and with an increased risk (OR=1.32,p=0.008) for the lowest quintile of eGFR after adjusting for age, BMI, and bloodpressures. However, such association was not observed in females (p>0.05). Thisassociation suggests MTHFR C677T polymorphism may play a role in the regulation of eGFR in males.Conclusion:MTHFR C677T is a risk factor for decreasing kidney function in Chinese males ofnorth Jiangsu, implicating this gene in the pathogenesis of chronic kidney disease(CKD).