Association Between Metabolic Syndrome And Chronic Kidney Disease And The Kidney Pathological Anaylsis

Background/ObjectiveChronic kidney disease(CKD)is a widely recognized public health issue and associated with high morbidity,high mortality,tremendous health care expenditures and low awareness.Most clinical symptoms of CKD patients occured hiddenly.Indeed,the prevalence of CKD appeared to be rising rapidly with increased life expectancy,especially among the poor require more social attention in developing nation.It was estimated that approximately 119.5 million people have CKD and the prevalence of CKD is 10.8-13%in China in recent studies.With the improvement of living standards,lifestyle changes and aging of population in China,the incidence of metabolic diseases such as diabetes,obesity,hyperuricemia,hypertension and other chronic diseases gradually increased,resulting in the growth of incidence of secondary CKD.There is growing evidences that CKD shares many common risk factors with cardiovascular disease,such as decreased high-density lipoproteincholesterol(HDL-C)levels and smoking history,which are also associated to metabolic syndrome.Metabolic syndrome(MetS)is a common and usually underdiagnosed disease.entity,characterized by a cluster various of diseases,such as hyperglycaemia,hypertension,dyslipidaemia and visceral obesity.It has been proposed that this syndrome is a powerful determinant of diabetes and cardiovascular disease.MetS has become one of the major public-health challenges worldwide.It has been proposed that insulin resistance played a key pathogenic role in the development of MetS.Nevertheless,direct quantitative measurement of insulin sensitivity is laborious and complex and cannot be widely used as the diagnostic tool for MetS.Glycated haemoglobin(HbA1c)is a useful index of mean blood glucose and HbA1c may predict incident cardiovascular events,even in individuals without diabetes mellitus.Thus,some researchers proposed that HbA1c could be an important surrogate for MetS for several reasons.However,the cut-offs of HbA1 c and the conclusions were inconsistent.In recent years,a rise in the incidence of CKD and end-stage renal disease paralleled increasing prevalence of MetS.the association between MetS and CKD has been found in population-based cohorts and cross-sectional studies.Previous observational studies of US and Japan demonstrated that MetS was a significant risk of CKD.However,there are sparse datas on the association between MetS and CKD in a developing country such as China,where genetic and environmental backgrounds differ from those in Western countries.Besides,individual MS risk factors,such as blood pressure,body mass index and serum cholesterol concentration,have been shown to exhibit a paradoxical,inverse association with mortality in CKD populations.Insulin resistance is a central component of the metabolic dysregulation and insulin can act on virtually all renal cell types,including mesangial cells,podocytes and tubular epithelial cells.Only one study with smale sample reported the kidney pathological characteristics in individuals with MetS.Therefore,we conducted this researh,which includes four parts:First,we a conducted cross-sectional study to explore the prevalence of MetS,CKD in Chinese urban populations and examine the association of HbAlc with MetS and to determine whether HbA1c could be used as a simple method to select those at risk of MetS.Secondly,a retrospective cohort study was initiated to examine the relationship between the presence of MetS with the risk of CKD(eGFR<60ml/min/1.73 m2 or proteinuria)incidence in Chinese urban cohort.Thirdly,we systematically reviewed the prospective cohort studies around the world,as for the association between MetS and development of CKD.In the end,we compared the clinical and renal pathological features of MetS with non-MetS patients and evaluated the pathylogical parameters on the predictive value to the diagnosis of MetS related renal disease.Part I:Association between metabolic syndrome,HbAlc and chronic kidney disease in a Chinese urban population:a cross-sectional studyMethodsThe adults who visited the Health Checkup Clinic consecutively in Shandong Qianfoshan Hospital affiliated to Shandong University were enrolled in this tudy from April 2012 and ended in December 2013.Sociodemographic characteristics,and lifestyle behavior were obtained by means of questionnaire.High,weigh and blood pressure was measured,Blood was collected and serum creatinine,fasting blood glucose,haemoglobin,serum albumin and other biochemical index were measured.Protein in urine was measured.CKD was defined as decreased eGFR<60 ml/min/1.73m2 or presence of proteinuria(urine protein ≥ 1+).MetS was defined according to ATP III criteria.SPSS system 19.0 was used to perform all statistical analyses;significance levels were determined atp<0.05,two tailed.ResultsA total of 26,601 adults who visited the Health Checkup Clinic consecutively were enrolle.The mean age was 48.7±14.3 years;(range 18-92).Overall,36.4%(9,693)participants had MetS,3.0%had CKD(794).The prevalence of MetS in CKD group was higher compared with non-CKD group(58.4%vs.36.6%).The mean eGFR of MetS group was lower than the non-MetS group(98.20± 15.47 vs.104.44±15.3 ml/min/1.73m2).The porportation of proteinuria of MetS was higher than non-MetS group(3.1%vs.1.2%),the CKD prevalence was higher than non-MetS group.After adjustments were made for age,sex,smoking history and drinking habbit,MetS was significantly associated with higher prevalence of CKD(OR1.99,95%CI 1.57-2.53).As the number of components of MetS increased,the prevalence of CKD increased,mean value of eGFR decreased and prevalence of poteinuria also increased.Multivariable adjusted ORs for CKD in subjects with 3,4 or 5 MetS components were 1.82(95%CI 1.31-2.52,p<0.001),2.92(95%CI 2.09-4.09,p<0.001)and 3.07(95%CI 1.67-5.67,p<0.001),respectively.The participants were divided into four groups according to their HbA1c levels:QI(<5.7%),Q2(5.7-6.0%),Q3(6.0-6.5%)and Q4(≥6.5%).The proportion of participants with proteinuria in the four groups were 1.1%、1.7%、2.5%and 7.2%.The porportation of patients with renal insufficiency(eGFR<60ml/min/1.73m2)were 0.9%、1.4%、2.3%and 2.8%.The prevalence of CKD in the four groups were 1.9%、2.9%、4.4%and 9.3%.Logistic regression showed that compared with Q1 group,the multivariable adjusted ORs for MetS of Q2,Q3 and Q4 group were 1.94(95%CI 1.79-2.11)、3.08(95%CI 2.81-3.37)and 4.63(95%CI 4.18-5.14).The multivariable adjusted ORs for CKD were 1.24(95%CI 0.97-1.59),1.79(95%CI 1.44-2.24)and 3.26(95%CI 2.68-3.96).The multivariable adjusted ORs for proteinuria were 1.39(95%CI 1.01-1.92),2.20(95%CI 1.65-2.93)and 1.48(95%CI 4.28-6.91).The multivariable adjusted ORs for renal insufficiency 1.22(95%CI 0.86-1.73),1.45(95%CI1.06-1.99)and 1.40(95%CI 1.02-1.94).Multivariable linear regression analyses showed that with a 1%(11 mmol/mol)increase in HbA1c,OR for MetS was 1.95(95%CI 1.87-2.03),OR for CKD was 1.45(95%CI 1.36-1.54)and OR for proteinuria and renal insufficiency was 1.63(95%CI 1.52-1.74)and 1.12(95%CI 1.01-1.25)on multivariable analysis.The AUROC value of HbAlc was 0.69 for only MetS,0.67 for only CKD,and 0.75 for both MetS and CKD.The cutoff value was>5.55%for only MetS,>5.95%for only CKD,and>5.95%for both MetS and CKD.Sensitivity and specificity for predicting only MetS were 56.4%and 73.0%,respectively.Those for predicting only CKD were 44.3%and 80.9%,respectively,while those for predicting both MetS and CKD were 57.9%and 80.8%,respectively.Conclusions1.Prevalence of MetS in Chinese uban population was 37.3%.2.MetS was associated with high prevalence of CKD.There was a graded relationship between number of MetS components and prevalence of CKD,as well as the prevalence of proteinuria.3.High HbA1c was associated with higher MetS and CKD prevalence.4.Specificity of HbA1c to indicate MetS,MetS with CKD were higher than blood glucose,buth the sensitivity were lower.Part II:Metabolic syndrome increases the risk of chronic kidney disease in a Chinese urban populationMethodsThe adults who visited the Health Checkup Clinic consecutively in Shandong Qianfoshan Hospital affiliated to Shandong University from January to December 2008 were enrolle.Sociodemographic characteristics,such as age,gender,health history and lifestyle behaviour were obtained by means of questionnaire.High,weigh and blood pressure was measured,Blood was collected and serum creatinine,fasting blood glucose,haemoglobin and other biochemical index were measure.Urinary albumin was determined.The participants were followed for 5 years.SPSS system 19.0 was used to perform all statistical analyses;significance levels were determined at p<0.05,two tailed.Results293 participants were lost to follow-up,344 participants were excluded for new development of Met,and 230 participants who did not have complete clinical datas.In total,3663 participants were enrolled.Mean age was 45.1±13.8y.31.5%(n=1153)participants had MetS.Mean eGFR of participants was 98.60±14.25ml/min/1.73m2.After 5 years of follow-up,the average drop of eGFR was 2.99ml/min/1.73m2.Four percent(n = 145)of the analytic cohort developed CKD.The incidence of CKD in subjects with MetS was higher than no-MetS subjects(6.6%Vs.2.7%).In multivariate analysis,MetS significantly increased the development of CKD(OR 1.57;95%CI 1.10-2.22),renal insufficiency(OR1.41;95%CI 0.80-2.25)and proteinuria(OR 1.70;95%CI 1.12-2.58).The adjusted ORs of new CKD incidence in subjects with 4 and 5 components of MetS were 2.03(95%CI1.01-4.07)and 11.54(95%CI 1.03-131.53).The adjusted ORs of proteinuria incidence in subjects with 4 and 5 components of MetS were 2.18(95%CI 1.00-4.75)and 19.62(95%CI 1.72-223.46).Among the possible combinations of three MetS components,the combination of low HDL(High Density lipoprotein-cholesterol),elevated triglycerides and obesity was associated with the highest odds of CKD.The next combination was high blood pressure,elevated triglycerides and obesity.In subgroup analysis,multivariate regression analysis showed high blood pressure(OR 2.09;95%CI 1.31-3.35)independently increased incidence of new CKD at follow-up.Obesity increased incidence of renal sufficiency(OR 1.99,95%CI 1.01-3.92).High blood pressure increased incidence of proteinuria(OR 2.37,95%CI 1.35-4.18).Besides,MetS seemed to increase risk for new CKD(OR 1.55;95%CI 0.97-2.45)and proteinuria(OR 1.47;95%CI 0.85-2.56)in high blood pressure group,but no association was found in normal blood pressure group.After grouping the participants by other MetS components,ORs were not different.Conclusions1.The incidence of CKD was higher and the renal function declined faster in MetS group than non-MetS group2.MetS increased risk for CKD.The more the compnents of MetS,the higher the risk of CKD4.Elevated blood pressure increased risk for CKD and proteinuria.Obesity increased risk for renal insufficiency.Part III:Metabolic syndrome and kidney disease:A systematic review and Meta-analysisMethodsA comprehensive research was conducted of MEDLINE,the Web of Science CNKI,CNKI and WanFang technological periodical database for prospective cohort studies.Risk estimates for CKD were extracted from individual studies and random effect model was used as pooling method.STATA 15.0 was used to perform meta analysis;significance levels were determined at p<0.05.ResultsThirteen studies that met criteria were selected were included,and 21,8590 participants were enrolled.MetS was significantly associated with the development of CKD(OR 1.57;95%CI 1.20-2.05),eGFR<60 ml/min per 1.73 m2(OR 1.56;95%CI 1.34-1.82)and proteinuria(OR 1.48;95%CI 1.10-1.99).The strength of the association with CKD seemed to increase as the number of components of MetS increased.OR for CKD for elevated blood pressure was 1.69(95%CI 1.31-2.17),for elevated triglycerides was 1.29(95%CI 1.12-1.48),for low HDL cholesterol was 1.23(95%CI 1.10-1.37),for obesity was 1.36(95%CI 1.21-1.53)and for impaired fasting glucose was 1.10(95%CI 1.01-1.21).Conclusions1.Meta analysis showed that MetS increased incidenc of CKD,renal insufficiency and overt proteinuria.2.With the increasing of MetS’ components,the risk of CKD increases.3.Elevated blood pressure was more significantly associated with increased risk for renal insufficiency than other components of MetS.Part IV:Kidney Pathological Changes in Metabolic Syndrome MethodsWe retrospectively screened clinical information for patients who underwent percutaneous renal biopsy for renal injury between January 2016 and June 2018 in Shandong qianfoshan hospital,China.According to the clinical characteristics,they are divided into MetS group and non-MetS group.Results55 patients with MetS were identified,117 age-and sex-matched patients who did not have the criteria for MetS were used as controls.Baseline characteristics were similar between the 2 groups.On histopathologic examination,patients with MetS compared with controls had a greater prevalence of glomerulosclerosis(p=0.03),thickened bowman’ s capsule wall(p=0.02),bigger glomerular volume(p=0.002),and mesangial matrix expansion(p=0.03).Besides,presence of arterial sclerosis and hyaline degeneration were more more prevalent in patients with MetS(p=0.001).The most common renal diseases in the two group were both membranous nephropathy,but the IgA nephrology(18.20%vs.11.10%),diabetic nephropathy(16.36%vs.6.8%),and focal segmental glomerulosclerosis(12.73%vs.4.24%)were more common in MetS patients compared with non-MetS patients.In multivariate logistic-analysis,MetS appeared to increase incidence of FSGS and IgA nehprolgoy,but not stastistic significant.Obesity was indenpendently associated higher FSGS(OR 6.99;95%CI 1.17-41.64)and IgA nephrolpgy incidenceis(OR 5.32;95%CI 1.28-22.11).Besides,high TG seemed to increase FSGS incidence(OR 23.54;95%CI 1.64-337.78)and low HDL cholesterol seemed to decrease the FSGS incidence(OR 0.0;95%CI 0.003-0.92).Conclusions1.Renal glomeruloscleros,bigger glomerular volume,mesangial matrix expansion and arterial sclerosis were more obviouis in MetS patients.2.IgA nephrology and FSGS was more common in MetS patients.3.Among MetS components,obesity was a risk factor for IgA nephrology.