Study On Factors Affecting The Sudden Death Of Dialysis Patients And Association Of Visceral Adiposity Index With Chronic Kidney Disease

BackgroundThere is a increasing prevalence for both chronic kidney disease(CKD)and end stage renal disease(ESRD)in the worldwide with the improving of people’s living standard and medical technology and extending of average life-span.The people with CKD and ESRD are more younger than before.The main treatments for renal replacement therapy in patients with ESRD include hemodialysis,peritoneal dialysis and renal transplantation.The living of a great number of patients depend on maintenance hemodialysis(MHD)because of lacking of kidney source,poor physical condition,complications after transplantation,side effects of long-term using of immunosuppressive agents and so on.However,the mortality of dialysis patient remains relatively high as a result of many limitations of hemodialysis technology and other factors.Hemodialysis sudden death is defined as unexpected non-traumatic sudden death occurs in memodialysis patients after acute symptoms within one hour before the onset of symptoms and without syndrome of threatening life..There is often higher sudden death rate in maintenance hemodialysis patients with hypertension,heart failure or other complications.The topic of hemodialysis sudden death is hot internationally.However,there are rare in-depth studies of hemodialysis sudden death in our country.In order to improving MHD patient survival rate,analysis of the potential risk factors of sudden death in MHD patients was conducted in the first chapter of this study.As mentioned above,the incidence of CKD is rising and the bad outcomes of CKD were CRF and ESRD.There is an increasingly heavy economic burden to the society with the rising prevalence of CKD,CRF and ESRD.CKD has been paid more attention in the world as a global public health problem and the early prevention and treatment of CKD is particularly urgent.Obesity-related glomerulopathy(ORG)is closely associated with CKD.Abdominal obesity,especially visceral obesity,is more related with CKD when compared to subcutaneous obesity.Body mass index(BMI),waist circumference(WC),magnetic resonance imaging(MRI)are commonly used diagnostic tool for characteristical generalized obesity.Compared with above maters,mounting evidence imply that visceral adiposity index(VAI)may be a more ideal measure of obesity,especially when used to assess disease risk.VAI,the scoring system that based on both anthropometric(BMI and WC)and metabolic(triglycerides,high-density lipoprotein,cholesterol)parameters,is capable of indicating both fat distribution and function and it has been proposed as a surrogate marker of adipose tissue dysfunction.VAI is highly correlated with visceral adiposity measured by MRI,the gold standard method.Studies showed that there is association between VAI and many chronic disease,such as diabetes mellitus(DM),cardiovascular disease(CVD),hypertension and so on.However,less is known about the predictive performance of VAI for CKD.Neither is known about a VAI level corresponding to the threshold of such risks.We hereby extrapolated VAI to estimate the visceral adiposity dysfunction associated with CKD.Objective1.To analyze the potential risk factors of sudden death in maintenance hemodialysis patients.2.Explore the relationship between VAI and the prevalence of CKD for slowing or even reducing progression to ESRD.Methods1.Study on factors affecting the sudden death of dialysis patients1.1 SubjectsThis was a retrospective study.A total of 166 MHD patients were recruited into our study.There were 103 males aged 54.43± 17.40(mean±SD).There were 63 females aged 54.76± 15.44(mean±SD).Among them,the patient number respectively with an etiology of chronic glomerulonephritis,hypertension,diabetes,stones and obstruction or uncertain etiology was 109/166(66%),32/166(19%),14/166(8%),7/166(4%)and 4/99(2%)respectively.1.2 Data collection(1)Basal characteristics:sex,age,primary disease as the etiology,maintain dialysis time and interval,dialysis model(HD,HD+HDF and HDF,each for one time per week),systolic blood pressure(SBP)and diastolic blood pressure(DBP)of pre-dialysis and post-dialysis,diuretics(furosemide)dose,ultrafiltration,dialysis blood flow(the patient could tolerate).(2)Laboratory parameters:serum potassium,calcium and phosphorus,albumin and the degree of anemia.(3)Clinical indicators:blood pressure during dialysis,coronary heart disease(myocardial infarction,ischemic attack)and a history of congestive heart failure.1.3 DefinitionsDiagnostic criteria for sudden death:unexpected non-traumatic sudden death,death occurs after acute symptoms within one hour before the onset of symptoms and without syndrome of threatening life.Sudden death occured in the hospital could reffer the dialysis records and in-patient medical records.Sudden death occurred outside the hospital were diagnosed based on the research team investigation including the accounts of patient family and witness.Sudden death occured in sleep were recruited into sudden death group.1.4 Statistical analysisData were analyzed by using Stata 11.0.All patients were divided into sudden death group or no-sudden death group.The continuous variants were presented as mean±standard deviation if they had a normal distribution or median and interquartile range if they had a skewed distribution.The categorical variants were presented as absolute and relative(%)values or proportion.A two-tailed P value<0.05 was defined as statistically significant.2.Association of visceral adiposity index and chronic kidney disease2.1 Subjects and recruitmentData was collected from a population-based,cross-sectional survey performed in Wanzai Town from June,2012 to October,2012 and in Guangzhou from January,2013 to May,2013.We invited all residents over 18 years age to take part in our survey.Participants were invited by mail and home visits,of whom 2082 subjects participated in the study.We excluded the subjects with missing data or age less than 40 years.This study was supported by the Ethics Committee of the Third Affiliated Hospital of Southern Medical University.All subjects signed informed consents.The study was conducted by complying with the principles of the Declaration of Helsinki.2.2 Data collectionAll medical staff performing the survey had got systematic training.Data was collected in local community clinic,health stations or at resident home.Data of age,sex,education,alcohol use,current or past cigarette smoking,physical activity and personal history and family history were achieved by using questionnaires.The subjects with lipid regulation drugs and angiotensin converting enzyme inhibitor/angiotensin II receptor antagonist treatment nearly a month were excluded.A total of 2082 people included in this study.2.3 Anthropomorphic measurementsBlood pressure was determined with the calibrated mercury sphygmomanometer in a sitting position after at least 5 minutes rest.The mean value of the three times of measurements was calculated.Weight and height were measureed.WC was measured according to WHO guideline;at the mid-point between the lower border of the rib cage and the iliac crest.BMI was calculated as weight(in kilograms)divided by the square of the height(in meters).2.4 Laboratory testAll blood specimens were collected from all participants in a local community clinic after an overnight fasting for at least 10 hours.Fresh morning urine samples were collected.Women who were actively menstruating and subjects having urinary tract infection symptoms were excluded from the urine test.All specimens from collection sites were transported to the central laboratory in the Third Affiliated Hospital of Southern Medical University in 3 hours and stored at 2-8 ℃ until analysis.Urinary albumin was measured by an immune nephelometric method.Serum insulin was measured using electro-chemiluminescence immunoassays.Urinary creatitine,serum creatinine,fasting glucose,serum total cholesterol,serum triglyceride and serum high density lipoprotein cholesterol were measured by colorimetric methods.High sensitivity C-reactive protein(CRP)was measured by using an enzymatic immunoassay turbidimetric method.2.5 Calculation formulaHomeostatic model assessment of insulin resistance(HOMA-IR)was calculated as fasting plasma glucose(mmol/L)X fasting insulin(mU/L)/22.5.Glomerular filtration rate was estimated by using the Chineses-Modification of Diet in Renal Disease(C-MDRD)equation[175 X(Scr)-1.234 X(Age)-0.179 X(if female,X 0.79)].Urinary albumin to creatinine ratio(ACR,mg/g)was calculated as the ratio of urinary albumin output to urinary creatitine output.The VAI was calculated according to the definition established by Amato and colleagues:Males:VAI=[WC/39.68+(1.88 X BMI)]X(TG/1.03)X(1.31/HDL)Males:VAI=[WC/36.58+(1.89 X BMI)]X(TG/0.81)X(1.52/HDL)2.6 DefinitionsThe estimated glomerular filtration rate(eGFR)was estimated using a formula from the Chinese-Modification of Diet Renal Disease(C-MDRD)study:eGFR(ml/min/1.73 m2)= 175 ×(Scr)-1.234 ×(Age)-0.179 ×(if female,× 0.79).Reduced renal function was defined as an eGFR of less than 60 ml/min per 1.73m2.For practical purposes,albuminuria was defined as a spot urinary albumin-to-creatinine ratio(ACR)higher than 30 mg/g.CKD was defined as an eGFR of less than 60 ml/min per 1.73 m2 or albuminuria.Hypertension was defined as a blood pressure(BP)of 140/90mmHg or higher or receiving treatment for previously diagnosed hypertension.Determination of diabetes is a fasting blood glucose(FBG)of 7.0 mmol/1 or higher or with previously diagnosed type 2 diabetes.The socioeconomic factors were recorded in our study.2.7 Statistical analysis.Data were analyzed by using SPSS version 19.0(SPSS Inc,Chicago,IL).All paticipants were divided into four groups based on VAI at four quartiles.The continuous variants were presented as mean ± standard deviation if they had a normal distribution or median and interquartile range if they had a skewed distribution.For multiple comparisons,Bonferroni correction was used to adjust P-values.The categorical variables were presented as absolute and relative(%)values or proportion.Logistic regression models were used to examine the cross-sectional association between VAI at four quartiles and the prevalence of CKD in different subpopulations.Estimated odds ratios(OR)and 95%confidence intervals(CI)were recorded.Subjects in group 1 served as the reference group.For each gender,Model 1 was adjusted for age,sex;Model 2 was adjusted for age,sex,history of hypertension,history of coronary heart disease,current smoker,current alcohol use,high school or above and Model 3 was adjusted for above + systolic and diastolic blood pressure.A two-tailed P value of 0.05 was consided as statistically significant.Results:1.1.Study on factors affecting the sudden death of dialysis patients1.1 A total of 166 HD patients were recruited in this study.The total death rate was 20.48%.There were 21 male patients and 13 females in the sudden death group.There were 31 patients with chronic glomerulonephritis,2 patients with hypertension and 1 case with unclear causes.The rates of male and female were 20.39%,20.63%,respectively.1.2 Ratio of chronic glomerulonephritis as the etiology of ESRD in the sudden death was significantly higher than non sudden death group(P<0.01).1.3 The percentage of patients with average dialysis interval>96 hours in sudden death group was significantly higher than non sudden death group(14.7%vs 4.5%,P<0.05).The percentage of patients treated with diuretics in non sudden death group was significantly more than sudden death group(97.1%vs 87.9%,P<0.001).The percentage of patients with dialysis blood flow rate of 150-200ml/min in non death group was significantly higher than sudden death group(35.3%vs 56.1%,P=0.03).The patients with dialysis blood flow<150 ml/min do the opposite(5.9%vs 0,P=0.04).1.4 There are more patients with pre-dialysis DBP<60mmHg in sudden death group when compared to non-sudden death group(17.6%vs 4.5%,P = 0.009),and the patients with post-dialysis DBP 60-100mmHg do the opposite(55.9%vs 74.2%,P =0.037).There were more patients with history of myocardial infarction in sudden death group when compared to non sudden death group(14.7%vs 4.5%,P = 0.034).2.Association of visceral adiposity index and chronic kidney disease2.1 A total of 2082 subjects(718 males and 1364 females;mean age 57.41 士 10.93 years,range 40-95 years).Men had a lower participation rate than women because they have a higher employment outside home twon.2.2 Table 1 depicts the characteristics of subpopulations based on VAI quartiles in the entire cohort.Generally,the association of an increase of the VAI quartile with the accumulation of age had statistical significance(p<0.05).There was a significantly difference between the VAI quartile and history of hypertension(p<0.001)and history of diabetes(p<0.05).The increase of the VAI quartile is significantly positively correlated with an accumulation of BMI,WC,BP,fasting blood glucose,serum total cholesterol(TC),lower density lipoprotein(LDL),total triglyceride(TG),high-sensitive CRP(hs-CRP),serum uric acid(SUA),urinary albumin to creatinine ratio(ACR)and HOMA-IR(p<0.001).The VAI quartile was inversely related to the increasing of serum high density lipoprotein(HDL)and estimated glomerular filtration rate(eGFR),which has highly statistical significance(p<0.001).The VAI quartile was significantly related to the prevalence of CKD(p<0.001).2.3 The first,second,third and fourth quartile groups are<0.924,0.924≤-1.454,1.454≤-2.319,≥2.319,respectively.The odds ratio for CKD as compared with the first quartile of VAI is 1.33(95%CI 0.91-1.94,P =0.139)for the second one,1.995(95%Cl 1.35-2.80,P<0.01)for the third one,and 2.25(95%CI 1.57-3.21,P<0.001)for the fourth one after adjusting for age,sex with logistic models.The odds ratio for CKD as compared with the first quartile of VAI is 1.31(95%CI 0.87-1.96,P =0.19)for the second one,1.86(95%Cl 1.26-2.73,P =0.002)for the third one,and 2.08(95%CI 1.42-3.05,P<0.001)for the fourth one after adjusting for age,sex,history of hypertension,history of coronary heart disease,history of diabetes,physical inactivity,current smoker,current alcohol use and high school or above.The odds ratio for CKD as compared with the first quartile of VAI was 1.15(95%CI 0.72-1.83,P =0.569)for the second quartile,1.20(95%CI 0.75-1.90,P =0.452)for the third quartile,and 1.40(95%CI 0.88-2.22,P =0.156)for the fourth quartile when adding fasting glucose,systolic and diastolic blood pressure to the model.Conclusions1.Study on factors affecting the sudden death of dialysis patientsIt is suggested that longer maintaining dialysis time,average dialysis interval>96 hours,average dialysis blood flow<150 ml/min,pre-dialysis DBP<60mmHg and myocardial infarction history might be risk factors associated with sudden death of dialysis patient.Long time furosemide treatment for dialysis patient could reduce the risk of sudden death.2.Association of visceral adiposity index and chronic kidney disease2.1 VAI is highly associated with the prevalence of the CKD in population no less than 40 years.VAI ≧ 1.454 has predictive performance for the prevalence of the CKD when fasting glucose and blood pressure are considered.2.2 VAI can be used in the health service institutions of all levels and is expected as a new index for prediction of chronic kidney disease(CKD)in clinical work for its advantages of easily calculate,more reliable and cheaper.