Analysis Of Levels Of Serum Indoxyl Sulfate And Related Factors At Different Stages Of Chronic Kidney Disease Patients

Objective:Indoxyl Sulfate?IS?is a typical protein binding toxin and it can lead to injury of important target organs in patients with chronic kidney disease.The aim of this study is to investigate the levels of serum IS in different stages of chronic kidney disease.The effect of residual renal function on the distribution of IS in the serum of the peritoneal dialysis patients.This study also further explore the relationship between the level of IS and related clinical factors as well as cardiovascular events.Methods:This cross-sectional observational study included patients with chronic kidney disease hospitalized in the Department of Nephrology,Dalian Central Hospital,April-October 2017.The age of patients is 18-75 years old,CKD staging conforms to the diagnostic criteria for KDOQI chronic kidney disease in 2002.The general clinical datas and laboratory indexes were collected.Cardiac ultrasound related indexes:EF value,E/e'and Devereux formula to calculate LVMI.Electrocardio physiological indexes:PR interval,QRS long time,correction of QT interval?QTc?.The Serum IS level was detected by high performance liquid chromatography.All datas were analyzed by SPSS20.0 statistical software.Result:1.General information:A total of 266 patients were enrolled in this study.There were 37 cases of CKD1-2,44 cases of CKD3,45 cases of CKD4,46 cases of CKD5 non-dialysis,45 cases of peritoneal dialysis,49 cases of hemodialysis.This study include 160 males?60.2%?and 106 females?39.8%?,with an average age of58±11 years.The primary kidney disease was chronic glomerulonephritis in 100 cases?37.6%?,hypertensive nephropathy in 43 cases?16.2%?,diabetic nephropathy in 82cases?30.8%?,polycystic kidney in 11 cases?4.1%?,and other etiologies 30 cases?11.3%?.The history of cardiovascular 90 cases?33.7%?,diabetes history 126 cases?47.4%?,smoking history 87 cases?32.7%?,BMI 25.4±4.1 kg/m².2.IS level in different CKD stages:CKD1-2 was 0?0-0.4?mg/L,CKD3 was 0.5?0-3?mg/L,CKD4 was 2.7?0.9-10.4?mg/L,CKD5 non-dialysis was 12.1?4.6-25.5?mg/L,PD was 31.1?22.3-44.2?mg/L,HD was 28?19.4-37.1?mg/L,The difference between each group was statistically significant,P<0.01.There was no significant difference in plasma IS concentration between the PD patients and HD Patients,P=0.45.According to the residual urine volume,the peritoneal dialysis patients were divided into non-anuric group 24 patients and anuric group 21 patients,IS concentrations were28.57+17.87mg/L vs 38.68+16.14mg/L the difference was statistically significant P=0.05.3.The correlation between IS level and clinical indicators:Spearman correlation analysis:systolicpressure?r=0.17,P<0.01?,ureanitrogen?r=0.68,P<0.01?,creatinine?r=0.83,P<0.01??CystatinC?r=0.80,P<0.01?,serum phosphorus?r=0.58,P<0.01?,alkaline phosphatase?r=0.37,P<0.01?,magnesium?r=0.34,P<0.01?,parathyroid hormone?r=0.48,P<0.01?,Cardiovascular events?r=0.27,P<0.01?,history of diabetes?r=0.15,P=0.01?,QTc?r=0.32,P<0.01?,LVMI?r=0.44,P<0.01?,E/e'?r=0.34,P<0.01?,the age of dialysis?r=0.27,P<0.01?,IS was positively correlated with these factors above.Glomerular filtration rate eGFR?r=-0.82,P<0.01??uric acid?r=-0.18,P<0.01??total cholesterol?r=-0.24,P<0.01??triglyceride?r=-0.14,p=0.02??low density lipoprotein?r=-0.19,P<0.01??high density lipoprotein?r=-0.28,P<0.01?,hemoglobin?r=-0.4,P<0.01??Ejection fraction?r=-0.17,P<0.01?,IS was negatively correlated with these factors above.The curve fitting equation of IS and eGFR is Y=151.1X^-0.94+11.8X^-0.94 R²=0.51.4.Comparation the laboratory indicators of high and low concentrations of IS in ESRD:The results showed that creatinine,Cystatin C eGFR,hemoglobin,albumin,serum calcium,alkaline phosphatase,total cholesterol,high density lipoprotein,LVMI were statistically significant in the two groups,P<0.05.5.The relationship between IS level and cardiovascular events:The history of cardiovascular diseases as the dependent variable,logistic regression analysis found that when IS is a continuous variable,univariate analysis,OR=1.023 P<0.01;model;1adjusting for age,sex,smoking history,diabetes,systolic blood pressure OR=1.024,P<0.01;model 2 adjusting for cystatin C,urea nitrogen,creatinine,uric acid OR=1.01 P=0.38;Model 3 adjusting for hemoglobin,total cholesterol,albumin,prealbumin OR=1.023 P<0.01,model 4:adjusting for serum calcium,phosphorus,alkaline phosphatase OR=1.021 P=0.02.When IS is classified as two variables?median demarcation?,univariate analysis,OR=2.632 P<0.01,model 1 OR=2.826 P<0.01,model 2 OR=1.782 P=0.15,model 3 OR=2.693 P<0.01,model 4 OR=2.398 P<0.01.Conclusion:?1?With the progress of chronic kidney disease,the total IS level increased gradually.It showed a strong negative correlation with glomerular filtration rate,reached the peak in maintenance dialysis patients.Residual renal function plays an important role in the clearance of IS,suggesting that protecting the residual renal function may have an significant effect on protein toxin clearance.?2?The plasma levels of IS in CKD patients were mainly related to renal function,calcium and phosphorus metabolism,nutritional status,myocardial hypertrophy and cardiac function.?3?In CKD patients adjusting for traditional risk factors,calcium and phosphorus metabolism and nutrition related indicators respectively,the plasma IS level is still independently associated with cardiovascular events,suggesting that the total IS level may be an important factor for cardiovascular disease progression and it is one of the intervention target on the treatment of CKD patients.