Prevalence And Risk Factors Of Chronic Kidney Disease And Diabetic Kidney Disease In Central Henan Province

BackgroundThe prevalences of chronic kidney disease（CKD）and diabetic kidney disease（DKD）significantly increased in the past decades.Both CKD and DKD have been a global health issue because of the anonymous symptoms,insufficient awareness,and rapid progression in their late stages.In China,dozens of potential risk factors,such as unhealthy diet,hypertension,diabetes,dyslipidemia,and metabolic syndrome,are suggested to be associated with increasing prevalences of CKD and DKD.In addition,the prevalences of hypertension,diabetes and metabolic syndrome are also increasing along with the high-speed economic and social development and varied dietary pattern.Previous studies have also demonstrated that the prevalence of CKD varies substantially among geographical regions.This diversity might be associated with the variability in diet pattern,lifestyle,education,and economic condition.Comparing with developed countries,epidemiological studies of CKD and DKD are relatively lacking in China.In addition,there is not any epidemiological studies that focus on both CKD and DKD in population from Henan province.The social and economic development in Henan has continued to develop rapidly.The working pattern and lifestyle have also changed significantly.Do these changes have corresponding effects on the prevalence of CKD and DKD?What kinds of risk factors for CKD and DKD are covered in Henan residents?Whether these risk factors are different between rural and urban residents?Following the development of genome-wide association study（GWAS）in the past decades,thousands of genes,which are proved to be associated with higher risk of disease,are reported.By employing these research results,single nucleotide polymorphisms（SNPs）could be used as instrumental variables in mendelian randomization（MR）studies and to calculate the causal effects between exposure and outcome.Under current circumstances,we conducted two cross-sectional surveys to evaluate the prevalences of CKD and DKD in rural and urban population in Henan province.The MR analysis was employed to estimate the causal effects between the risk factors and renal damage indicators.This study aimed at providing the latest epidemiological data and offering scientific evidences for early intervention and prevention strategies for CKD and DKD.Chapter 1 Prevalence and risk factors of chronic kidney disease and diabetic kidney disease in rural populationMethodsThe subjects were recruited in 4 rural districts of Henan province using a multistage,stratified cluster sampling method to select participants aged over 18 years old in general population.Data were collected by face-to-face interview in examination centers at local health stations.All subjects completed a questionnaire recording their sociodemographic status,personal and family health history,awareness and control of chronic non-communicable disease,lifestyle,and dietary pattern with assistance of medical students,trained practitioners,doctors and nurses.Estimated glomerular filtration rate（e GFR）was calculated by the 2009 CKD-EPI creatinine equation.Albuminuria was defined as participants with an ACR>30mg/g.CKD was defined as participant has an e GFR less than 60 m L/min/1.73m² or albuminuria.DKD was defined as participants has diabetes and CKD.Standard population of this study was using the data from the China Population Sampling Census in 2009.Results1.A total of 23869 participants were involved in this study.Mean age was 56.43±13.12 years old and men to women ratio was 1:1.49.Totally,4347 participants were suffering from CKD,in which 962 subjects were DKD patients.The overall prevalence of CKD and DKD was 16.4%（95%CI:15.9–16.8%）and 2.9%（95%CI:2.7–3.1%）,respectively.There were 635 individuals performed e GFR less than 60 m L/min/1.73m²and 3947 individuals performed albuminuria.The adjusted prevalence was 2.7%（95%CI:2.5–2.9%）and 15.0%（95%CI:14.6–15.5%）,respectively.2.Subjects with middle level of education or family income performed lower CKD prevalence of 13.4%(95%CI:12.7–14.1%,P _trend<0.001)and 13.8%(95%CI:12.9–14.7%,P _trend<0.001),respectively.However,those with the highest education and family income had the lowest DKD prevalence of 1.5%(95%CI:1.2–1.7%,P _trend<0.001)and 2.5%(95%CI:2.1–2.8%,P _trend=0.03),respectively.3.Results of binary logistic regression demonstrated that increased age,education,upper family income,current smoker,diet rich in fruits and vegetables,unhealthy BMI,diabetes,hypertension,dyslipidemia and hyperuricemia were associated with higher risk of CKD and DKD.Having the combination of diabetes,hypertension and hyperuricemia is performing the highest OR for developing CKD.Restricted cubic splines（RCS）showed that increased concentration of serum glucose,uric acid and cholesterol were associated with higher risk of CKD.4.Results of ordinal logistic regression showed that high fat diet,diabetes,hypertension,dyslipidemia and hyperuricemia were independent risk factors for progression of severity of albuminuria.Increasing age,habitual alcohol consumption,diet rich in fruits and vegetables,heavy physical activity,diabetes,hypertension,dyslipidemia and hyperuricemia were independent risk factors for declination of renal function.Conclusion1.The prevalence of CKD and DKD is still high in Henan rural population.2.Diabetes,hypertension,dyslipidemia and hyperuricemia are major risk factors for CKD and DKD in Henan rural population.3.Diabetes,hypertension,dyslipidemia and hyperuricemia are also major risk factors for declination of renal function in Henan rural population.Chapter 2 Prevalence and risk factors of chronic kidney disease and diabetic kidney disease in urban populationMethodsThe subjects were recruited from Zhengfei communities in Zhengzhou,Henan province.A multistage,stratified cluster sampling method was employed to select participants aged over 18 years old in general population.Results1.A total of 5231 participants were involved in this study.Mean age was 42.52±16.51 years old and men to women ratio was 1:0.78.Totally,945 participants were suffering from CKD,in which 192 subjects were DKD patients.The overall prevalence of CKD and DKD was 16.8%（95%CI:15.8–17.8%）and 3.5%（95%CI:3.0–4.0%）,respectively.There were 132 individuals performed e GFR less than 60 m L/min/1.73m²and 858 individuals performed albuminuria.The adjusted prevalence was 2.8%（95%CI:2.4–3.3%）and 14.9%（95%CI:13.9–15.9%）,respectively.2.Subjects with upper level of education performed lower CKD and DKD prevalence of 17.9%(95%CI:16.7–19.0%,P _trend<0.001)and 3.7%(95%CI:3.1–4.2%,P _trend<0.001),respectively.Those with middle level of family income performed lower CKD and DKD prevalence of 20.0%(95%CI:18.2–21.8%,P _trend=0.01)and 3.1%(95%CI:2.3–3.9%,P _trend=0.01),respectively.3.Results of binary logistic regression demonstrated that increased age,current smoker,diet rich in fruits and vegetables,unhealthy BMI,diabetes,hypertension and dyslipidemia were associated with higher risk of CKD and DKD.Having the combination of diabetes,hypertension and dyslipidemia is performing the highest OR for developing CKD.RCS showed that increased concentration of serum glucose,uric acid and cholesterol were associated with higher risk of CKD.4.Results of ordinal logistic regression showed that increased age,current smoker,diet rich in fruit and vegetable,heavy physical activity,overweight,obesity,diabetes,hypertension and dyslipidemia were independent risk factors for progression of severity of albuminuria.Increasing age,smoking,diet rich in fruit and vegetable,obesity,diabetes,hypertension and dyslipidemia were independent risk factors for declination of renal function.Conclusion1.The prevalence of CKD and DKD is still high in Henan urban population.2.Increased age,unhealthy lifestyle and BMI,diabetes,hypertension,dyslipidemia are major risk factors for CKD and DKD.3.Older age,being current smoker,diet rich in fruit and vegetable,obesity,diabetes,hypertension and dyslipidemia are major risk factors for declination of renal function.Chapter 3 Validation of causal effect between risk factor and trait of renal function using Mendelian randomization analysisMethodsAdopting a two-sample Mendelian randomization（MR）approach we incorporated genome-wide association study summary statistics from UK bio-bank genetics consortium and CKD GEN consortium.Exposures included risk factors discovered by our previous studies and outcomes were traits of renal function.The inverse variance weighting（IVW）method and wald ratio model were employed to estimate the causal effect.The Q test was applied for heterogeneity test and MR-Egger regression was employed to assess whether there were horizontal pleiotropic effects.Results1.By using decreased e GFR as exposure,the results showed that increased BMI and having hypertension were positively associated increased risk of CKD.The odds ratios were 1.16（95%CI:1.05–1.29）and 3.97（95%CI:2.13–7.40）,respectively.Moderate and heavy physical activities,having diabetes and hyperlipidemia were not statistically causal associated with decreased e GFR.2.By using albuminuria as exposure,the results showed that increased BMI and having hypertension were positively associated increased UACR.The odds ratios were1.09（95%CI:1.04–1.13）and 1.58（95%CI:1.28–1.95）,respectively.Moderate and heavy physical activities,having diabetes and hyperlipidemia were not statistically causal associated with elevated UACR.ConclusionThe increased BMI and having hypertension may play a causal role in CKD etiology and these are accordance with the results from our former epidemiological studies.By adopting MR approaches,we could avoid the bias from unmeasured confounders or reverse causation and improving the stability and reliability.Conclusions of whole study1.The prevalence of CKD and DKD is very high in Henan population.2.Increased age,unhealthy lifestyle and BMI,diabetes,hypertension,dyslipidemia and hyperuricemia are major risk factors for CKD and DKD.3.MR analysis indicates that elevated BMI and having hypertension have causal effects on declination of renal function.Innovation points of current study1.Our current study reported the overall prevalences of CKD,DKD and two different renal indicators,and that in participants from different stages of education and family income by conducting a large sample cross-sectional study including both rural and urban participants from Henan province.2.We calculated risk factors for renal damage using binary and ordinal logistic regression and evaluated the non-linear association between risk factors and renal outcome by using restricted cubic spline.Our results could provide the latest data and scientific evidences to develop prevention and intervention strategy for CKD and DKD.3.Based on the results of cross-sectional study,we further employed MR analysis to calculate the causal effect between risk factors and renal indicators and it showed that the increased BMI and having hypertension may play a causal role in CKD.