Discussion On "Turbid Poisonous Veins" In CKD Based On Vascular Endothelial Injury Induced By Intestinal Uremic Toxin

Background:Chronic kidney disease(CKD)has become a worldwide public health problem as a group of chronic kidney diseases that pose a serious threat to human health and life and cause severe economic burdens.In the past 20 years,it has become the second fastest-growing disease.The risk of CKD patients dying from cardiovascular disease prematurely is much higher than the risk of dialysis or transplantation.Therefore,prevention of CVD in patients with CKD has always been the focus of research for kidney disease workers.Epidemiological investigations have shown that this high risk cannot be fully explained by classical cardiovascular risk factors.As research progresses,uremic toxins gradually enter the field of researchers and become a key factor in explaining high-risk CVD in patients with CKD.The European uremic toxin team classifies them according to the source of uremic toxins:(1)endogenous metabolites:self-metabolizing toxins,such as Asymmetric Dimethylarginine(ADMA),symmetry Symmetric Dimethylarginine(SDMA);(2)Microbial metabolites:mainly metabolites of the intestinal flora,so also known as enterogenous uremic toxins,such as p-cresol sulfate(p-Cresyl Sulfate,pCS),Indoxyl sulfate(IS);(3)Exogenous ingested substances:such as oxalate.The enterogenous uremic toxins produced by the metabolism of intestinal flora have attracted the attention of researchers at home and abroad due to their extensive biological toxicity,high protein binding rate and low removal efficiency.Among them,pCS and IS have become the research focus of enterogenous uremic toxins due to their strong cardiovascular toxicity and nephrotoxicity.Although a large number of in vitro experiments have proved that pCS and IS have strong cardiovascular and renal toxicity,and found that both pCS and IS are found.It can cause vascular endothelial injury through cellular immunity,but clinical trials have failed to prove the correlation between serum total pCS,IS and end point outcome.Therefore,in clinical research,the exploration direction of pCS and IS has shifted from serum total concentration to serum free concentration.Modern medicine has not made breakthroughs in intervention therapy.In recent years,Chinese medicine has accumulated rich experience in delaying the progress of CKD,preventing complications,and improving the prognosis.Now doctors believe that the research on the etiology and pathogenesis of CKD Chinese medicine believes Spleen and kidney decline,wet turbidity is the key pathogenesis of this disease,the significant effect achieved by turbidity treatment of CKD.In recent years,studies on intestinal uremic toxins have found that it has a certain correlation with "turbidity".Treatment of CKD by turbidity reduction can reduce the levels of pCS and IS in serum.At the same time,enterogenous uremic toxins lead to cardiovascular complications and Chinese medicine"turbidity and poisonous veins" theory has certain compatibility.To this end,this study preliminarily explored serum t-pCS,t-IS,f-pCS,f-IS,wet turbid syndrome syndrome scores,clinical indicators and indicators of reactive cellular immunity/inflammation damage(Neopterin,Npt)Correlation;explore the correlation between serum t-pCS,t-IS,f-pCS,f-IS,wet turbid syndrome syndrome,new sputum and vascular endothelial injury index ADMA;this study is to compare serum serum t-pCS The difference between t-IS,f-pCS,and f-IS in clinical indicators and wet turbidity syndrome.Investigate the potential mechanism of pCS and IS to induce vascular endothelial injury through cellular immunity,and explore its correlation with the theory of "turbidity and toxic pulse" in Chinese medicine,so as to treat chronic kidney disease and prevent cardiovascular complications for clinical treatment of dampness and turbidity Provide an objective basis.Objectives:1.This study preliminarily explored the correlation between serum t-pCS,t-IS,f-pCS,f-IS,wet turbid syndrome syndrome,clinical indicators and indicators of reactive cellular immunity/inflammatory injury.2.To explore the correlation between serum t-pCS,t-IS,f-pCS,f-IS,wet turbid syndrome syndrome,new sputum and vascular endothelial injury index ADMA.3.This study is to compare the correlation between serum t-pCS,t-IS,f-pCS,and f-IS in clinical indicators and wet turbidity syndrome.The purpose of this study is to explore the potential mechanism of enterogenous uremic toxins involved in vascular endothelial injury,and to explore the relationship between the pathological chain of "intestinal uremic toxin accumulation-inflammation-endothelial injury”and TCM syndromes,in order to further explore the turbidity The pathological essence of the wound vein,and provide clinical evidence for the theory of "turbidity and poisonous veins" of Chinese medicine,and find potential therapeutic targets for comprehensive prevention and treatment of CKD.METHODS:Clinical data and blood samples were collected from 137 patients who met the criteria for inclusion in the cross-sectional study.The serum t-pCS,t-IS,f-pCS,and f-IS concentrations were measured by high performance liquid chromatography-fluorescence(HPLC-FLD).The serum Npt and ADMA concentrations of the patients were measured using an ELISA kit.To analyze the correlation between serum t-pCS,t-IS,f-pCS,f-IS and clinical common indicators,Npt,ADMA,wet turbidity syndrome scores,and blood stasis syndrome scores;compare carotid intima-media thickening group with Blood t-pCS,t-IS,f-pCS,f-IS,Npt,ADMA concentration,wet turbidity syndrome score,blood stasis syndrome scores,etc.between non-thickening group,left ventricular hypertrophy group and non-hypertrophic group The difference of serum t-pCS,t-IS,f-pCS,f-IS,Npt,ADMA and clinical comparison between the wet and phlegm syndrome group and the non-dampness syndrome group,blood stasis syndrome group and non-blood stasis syndrome group Differences in common indicators.Results:1.With the loss of renal function in patients with CKD,the serum total and free intestinal uremic toxins increased progressively,and the serum Npt concentration also increased progressively.2.There was a significant positive correlation between Npt and serum t-IS and f-IS(r=0.659,P<0.001;r=0.664,P<0.001);positive correlation with serum f-PCS(r=0.356,P<0.039),showed no correlation with serum t-PCS(r=0.318,P=0.067).There was a significant positive correlation between H-CRP and t-PCS(r=0.27,P=0.01),and positive correlation with f-PCS and f-IS(r=0.216,P=0.04;r=0.258,P=0.014).There was no correlation between t-IS(P=0.059).There was a significant positive correlation between CRP and f-PCS and f-IS(r=0.253,P=0.005;r=0.251,P=0.005),and positive correlation with t-PCS and t-IS(r=0.204,P=0.024;r=0.23,P=0.011).There was a significant negative correlation between WBC and t-PCS(r=-0.236,P=0.006),and negative correlation with f-PCS(r=-0.19,P=0.026),serum t-pCS,t-IS,f-pCS Both f-IS and inflammatory markers are positively correlated.3.Studies have shown that serum unscent PCS,uncle IS,F-PCS,F-IS are significantly positively correlated with wet turbidity syndrome scores(P<0.01),and statistics between wet turbidity syndrome group and non-dampness syndrome group The difference between the ton-PCS,T-IS,F-PCS and F-IS groups was significant(P<0.01),and the "T-PCS" obtained by logistic regression was an independent risk factor for wet turbidity(OR=1.045).(95%Cl:1.000?1.092)).4.The comparison between the carotid intima-media thickening group and the non-thickening group showed that there was a statistical difference between the deuterium PCS and the wet turbidity syndrome points.Further logistic regression showed that the"wet turbidity syndrome score" in patients with age>55 years old CKD Independent risk factors for carotid intima thickening(OR=1.128(95%CI:1.014-1.256)).5.The comparison between left ventricular hypertrophy group and non-hypertrophic group showed that the difference between t-PCS,f-PCS,t-IS and f-IS groups was significant(P<0.01),and logistic regression was performed to obtain "t-IS".An independent risk factor for left ventricular hypertrophy(OR=1.128(95%CI:1.014 to 1.256).6.There was a significant positive correlation between wet turbidity syndrome score and blood stasis syndrome score(r=0.392,P0.001),but serum t-pCS,t-IS,f-pCS,and f-IS were not associated with blood stasis syndrome.Sexuality did not show statistical differences between the blood stasis syndrome group and the non-blood stasis syndrome group.Logistic regression with the independent variable did not obtain independent risk factors.Partial correlation analysis showed that the t-pCS&f-pCS&t-IS&f-IS variables were controlled,and the wet turbidity scores and blood stasis scores were more statistically correlated(r=0.419,p<0.001).It suggests that the other material basis of the wet phlegm syndrome may be significantly correlated with the blood stasis score.Conclusion:This study showed that there was a significant correlation between pCS,IS and wet turbidity syndrome in intestinal uremic toxin,and t-pCS was an independent risk factor for wet turbidity syndrome,and it was initially confirmed in CKD patients aged?55 years.Wet turbidity syndrome is an independent risk factor for carotid intima-media thickening,which provides a theoretical basis for further investigation of turbidity and venom of CKD patients,and indirectly proves the pathological phenomenon of intestinal uremic toxin pCS in endothelial injury.Among the potential values,some of the evidence suggests that cellular immune responses may be involved.