The Relationship Between Serum Indoxyl Sulfate And The Left Ventricular Diastolic Function And Prognosis In Hemodialysis Patients

Objective:Indoxyl sulfate,a protein-bound uremic toxin,was found to be accumulated in body with a reduction in renal function.This,in turn,not only had nephrotoxin but also cardiovascular toxicity.Thus,it had adverse effect on clinical events.This study investigated the relationship between serum indoxyl sulfate and the left ventricular diastolic function and prognosis in hemodialysis patients.Methods:Hemodialysis patients were enrolled from the blood purification center,Dalian Central Hospital,March-September 2017.Inclusion criteria:(1)Age?18years;(2)Dialysis age>3 months.(3)Patients who are not taking drugs that regulate the intestinal flora.Exclusion criteria:(1)Age<18 years;(2)Patients with malignancy;(3)Patients with acute infection and cardiovascular events in the past 3 months.(4)Patients with hypertensive heart disease,hypertrophic cardiomyopathy,cardiac valve disease,hyperthyroidism.For the eligible patients,collecting clinical data,completing biochemical detection,and performing echocardiographic examination.Serum IS concentration was detected by high performance liquid chromatography(HPLC).Application of E/e'as the criteria for the determination of diastolic dysfunction:E/e'<8 with e'>8,left ventricular diastolic function is considered normal;E/e'<8 with e'>8,diagnosis of left ventricular diastolic dysfunction grade I;8<E/e'<15,diagnosis of left ventricular diastolic dysfunction grade II;E/e'>15,diagnosis of left ventricular diastolic dysfunction grade III.Clinical events included cardiovascular events and all-cause mortality.Cardiovascular events including death caused by cardiovascular system dysfunction,congestive heart failure,myocardial ischemia,myocardial infarction,arrhythmia,ischemic stroke,or a new peripheral vascular disease.The relationship between IS and E/e'was analyzed by linear regression and Kaplane-Meier method(factors were compared using the log-rank test)was used to estimate cumulative event-free rate of time to first cardiovascular event and all-cause mortalityl in hemodialysis patients with high indoxyl sulfate level(>34.2 mg/L)and low indoxyl sulfate level(?34.2 mg/L).All data analysis was performed using SPSS 17.0 software package,and P<0.05 was considered statistically significant.Result:128 hemodialysis patients were enrolled,with 81 males and 47 females.Age was(49.1±11.6)years old.Among them,78 patients(60.9%)with primary disease were glomerular disease,14 patients(10.9%)were diabetic nephropathy,26 patients(20.3%)were hypertensive nephropathycases,7 patients(5.5%)were polycystic kidney,2patients(1.6%)were lupus nephritis,1 patients(0.8%)was left kidney atrophy,right kidney removed.The serum IS level of hemodialysis patients in our center was significantly higher than that of the general population,as high as(34.2±12.4)mg/L.Serum IS level was positively correlated with albumin,urea,creatinine,phosphorus,LVDD,LAV,LAVI,LVMI,E/e'.The incidence of left ventricular systolic dysfunction was not high,and the incidence of left ventricular diastolic dysfunction was up to 95%,and most of them were moderate to severe diastolic dysfunction.According to E/e',patients were divided into two groups(diastolic function normal,light,moderate dysfunction group,E/e'<15;Diastolic severe dysfunction group,E/e'?15).The average IS level in the group of E/e'<15 was(28.8±6.9)mg/L,and in the group of E/e'?15 was(48.4±12.5)mg/L,and the difference between the two groups was statistically significant.P<0.01.BMI,dialysis age,LVDD,IVST,LAV,LAVI,LVMI,E/A were higher in the group of E/e'?15 than E/e'<15 group,while EF was lower than E/e'<15 group,and the difference was statistically significant.Other indicators were not statistically significant.Univariate linear regression shows that serum IS was positively correlated with E/e'(?=0.357,P<0.01).After adjusting for various factors,serum IS was still independent and positively correlated with E/e'(?=0.341,P<0.01).Multiple stepwise regression analysis of the clinical factors of E/e',the results showed that IS and P entered the equation(r=0.677,r~2=0.459).Regression equation:E/e'=3.728+0.315×IS+2.252×P.This suggested that the increase of IS and P was a risk factor for left ventricular diastolic dysfunction in hemodialysis patients.During the follow-up period,31 of the 128 patients had cardiovascular events,4 of them died,1 died of heart failure,1 died of severe pneumonia,and 2 died of cerebral hemorrhage.All patients were divided into two groups according to the mean value of serum IS,one group IS?34.2mg/L,and the other group IS>34.2 mg/L.The Kaplan-Meier method was used for survival analysis,and the results showed that the risk of cardiovascular events increased significantly in patients with high serum IS levels during the follow-up period(log rank P=0.001).The serum IS level in patients with cardiovascular events was higher than that in patients without cardiovascular events(P<0.01).Conclusions:The results of this study indicate the serum IS level of hemodialysis patients was significantly higher than that of the general population.The incidence of left ventricular systolic dysfunction in hemodialysis patients was not high,and the incidence of left ventricular diastolic dysfunction was high,and most of them were moderate to severe diastolic dysfunction.Serum IS was independent and positively correlated with E/e'and was an independent risk factor for left ventricular diastolic dysfunction.Serum IS level can be used as an important marker for predicting cardiovascular events in hemodialysis patients.