Study On The Correlation Between Indoxyl Sulfate And Renal Tubular Function Injury Indexes And TCM Syndromes In CKD Patient

Objective:By analyzing the serum indoxyl sulfate(IS)levels,clinical data and traditional Chinese medicine(TCM)syndrome scores of CKD patients,to screen out the factors affecting renal tubular function in chronic kidney disease(CKD)patients,and clarify the effect of IS on renal tubular injury.On this basis,to further analyze the correlation between serum IS concentrations,clinical data and TCM syndrome scores of CKD patients,with a view to providing a reference basis for the treatment of renal tubular injury in CKD and delaying the progression of CKD in TCM.Methods:This study used a cross-sectional study method to include patients who met the criteria for chronic kidney disease nadir in the outpatient clinics and wards of the Department of Nephrology,Guang’anmen Hospital,Chinese Academy of Traditional Chinese Medicine from August 2021 to August 2022.Clinical data including general information(name,gender,age,height,weight,blood pressure,duration of CKD,comorbidities),laboratory test indexes and TCM syndrome score were collected.Blood samples were collected from the enrolled patients and serum IS concentrations were measured by high performance liquid chromatography(HPLC)method.After data entry in Excel,statistical analysis was performed using IBM SPSS 25.0.The clinical data and serum IS concentration were analyzed by descriptive statistics.χ2 test,Fisher exact test and non-parametric test were used for comparison between groups.Spearman correlation and point two column correlation were used for correlation analysis.Multi-factor logistic regression was used for further analysis to determine the relationship between variables.ROC curves were plotted to analyze the predictive value of each influencing factor on the occurrence of renal tubular impairment in CKD patients.The difference was considered statistically significant at P<0.05.Results:A total of 164 patients with CKD were included in this study.Among them,33 were in CKD stage 1,36 in CKD stage 2,21 in CKD stage 3a,16 in CKD stage 3b,18 in CKD stage 4 and 40 in CKD stage 5.1 Results of analysis of tubular impairment in CKD patients1.1 The incidence of renal tubular impairment in patients with CKD stages 1,2,3a,3b,4 and 5 was 54.5%,63.9%,81.0%,87.5%,94.4%and 97.5%respectively,with a progressive increase with increasing CKD and a statistically significant difference(P<0.01).1.2 Patients with CKD were divided into groups with normal tubular function and groups with impaired tubular function based on the presence or absence of tubular impairment and compared between the groups.There were differences between the two groups in age,disease duration,systolic blood pressure,history of hypertension,history of diabetes,IS,serum creatinine(SCr),blood urea nitrogen(BUN),uric acid(UA),estimated glomerular filtration rate(eGFR),α1-microglobulin(αl-MG),β2-microglobulin(β2-MG),retinol binding protein(RBP),hemoglobin(HGB),Ca2+and Pi+,and the differences were statistically significant(P<0.05).In contrast,there was no statistical difference between male and female ratio,diastolic blood pressure,BMI,history of hyperlipidemia,urinary albumin to creatinine ratio(UACR),albumin(ALB),alanine transaminase(ALT),aspartate aminotransferase(AST),cholesterol(CHO),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),K+and HCO3-levels(P>0.05).1.3 The results of the correlation analysis between the indicators of renal tubular impairment(α1-MG,β2-MG,RBP)in CKD patients and the variables that differed between the group comparisons showed that positive correlation between disease duration,systolic blood pressure,history of diabetes,IS,SCr,BUN,CKD stage,Pi+ and indicators of renal tubular impairment(α1-MG,β2-MG,RBP)(P<0.05).Negative correlations(P<0.05)between eGFR,HGB and indicators of renal tubular impairment(α1-MG,β2-MG,RBP).Age,history of hypertension,UA and Ca2+levels,on the other hand,were incompletely correlated(at least one P>0.05)with indicators of renal tubular impairment(α1-MG,β2-MG,RBP).1.4 Multi-factor logistic regression analysis showed that IS,BUN,and HGB were the influential factors for renal tubular impairment in CKD patients(P<0.05).Of these,IS and BUN are risk factors,HGB is a protective factor.1.5 The ROC curve showed that the area under the curve for IS,BUN,and HGB to predict renal tubular impairment in CKD patients was 0.780,0.797,and 0.701 respectively,with diagnostic efficacy BUN>IS>HGB(P<0.05).2 Results of the analysis of factors related to serum IS concentrations in CKD patients2.1 The results of the correlation analysis between general information,clinical and biochemical indicators and serum IS concentrations in CKD showed that positive correlation between age,disease duration,systolic blood pressure,history of hypertension,history of diabetes,SCr,BUN,UA,UACR,K+,Pi+ and serum IS concentration(P<0.05).Negative correlation between eGFR,HGB,ALT,AST,CHO,HDL-C,HCO3-and serum IS concentrations(P<0.05).2.2 Multi-factor logistic regression analysis showed that disease duration,history of hypertension,BUN,β2-MG and K+were independently and positively correlated with serum IS concentration(P<0.05);HGB was independently and negatively correlated with serum IS concentration(P<0.05).3 Results of the analysis of the TCM syndrome scores3.1 The results of the correlation between the TCM syndrome scores and serum IS concentration and renal function in CKD patients showed that positive correlation between spleen and kidney qi deficiency syndrome scores and IS,SCr,BUN,α1-MG,β2-MG and a negative correlation with eGFR in CKD patients(P<0.05).Significant positive correlations were found between spleen and kidney yang deficiency syndrome scores and IS,SCr,BUN,α1-MG,β2-MG and RBP,and significant negative correlations were found with eGFR(P<0.01).Positive correlation between the qi and yin deficiency score and IS,α1-MG and β2-MG,and negative correlation with eGFR(P<0.05).No correlation between the liver and kidney yin deficiency syndrome scores and any of the renal function indicators(P>0.05).Positive correlation between the yin and yang deficiency scores and β2-MG only(P<0.05).Positive correlations(P<0.05)with IS,SCr,BUN,UACR,α1-MG,β2-MG and RBP and significant negative correlations(P<0.01)with eGFR for water dampness syndrome scores.Positive correlation between dampness-heat syndrome scores and β2-MG and RBP(P<0.05).Positive correlation between blood stasis syndrome scores and IS,α1-MG and β2-MG(P<0.05).Significant positive correlation between turbid toxin syndrome scores and IS,SCr,BUN,α1-MG,β2-MG and RBP(P<0.01)and significant negative correlation with eGFR(P<0.01).3.2 Differences in the syndrome scores of spleen and kidney yang deficiency,water dampness and turbid toxin between the group with renal tubular impairment and the group with normal renal tubular function in CKD patients(P<0.05).And patients in the CKD renal tubular impairment group had higher syndrome scores of spleen and kidney yang deficiency,water dampness and turbid toxin than those in the normal renal tubular function group.Conclusions:As renal function in CKD progresses,serum IS concentrations progressively increase and the more pronounced the changes in indicators of renal tubular function impairment.Significant correlation between serum IS concentrations and indicators of renal tubular impairment.With the increase in serum IS concentration in CKD patients,the syndromes of spleen and kidney qi deficiency,spleen and kidney yang deficiency,water dampness and turbid toxin in TCM becomes more and more obvious.Compared to CKD patients with normal renal tubular function,CKD patients with combined renal tubular impairment have more pronounced syndromes of spleen and kidney yang deficiency,water dampness and turbid toxin.