Efficacy And Safety Of YSQU Particles For Chronic Kidney Disease Stage3-4

Chronic kidney disease(CKD) is a group of development of progressive chronic non-infectious diseases which are characterized by high prevalence rate,high cardiovascular disease complications,high mortality and high consumption.It is a serious challenge which the developed or developing countries must to be faced.So, to strengthen the early diagnosis of CKD,monitor and control the progression of CKD and delay the progression of CKD to end-stage renal disease(ESRD) has important implications to the global public health,expercially to our developing county!Renal fibrosis is the final common pathway in which all CKD including primary, secondary kidney disease develop to ESRD.A variety of mechanisms are involved in the occurrence and development of renal fibrosis and include the activation of Renin-Angiotensin system(RAS) and abnormal glomerular hemodynamics which is associated with the activation of RAS,the abnormal expression of growth factors, cytokines and inhibitor of tissue plasminogen activatoro,the epithelial-mesenchymal transition(EMT) and the abnormal activation of Smad signal transduction pathway. Many recent studies found that advanced glycation end products(AGEs) and advanced oxidation protein products(AOPP) were a new class of uremic macromolecular toxin which were closely related with renal fibrosis.It is found that AGEs and AOPP are very similar in the formation approach,molecular structure and biological effects.The serum AGEs and AOPP accumulate at the stage of CRF of CKD because of the unique carbonyl stress and decreased renal clearance in this stage.They can induced the release of the inflammatory regulatory factors such as TNF-α,IL-8,IL-1 and NO,participated the progression of CRF and involed in oxidative stress and inflammatory reaction which improved the generationg of AOPP and AGEs by combination with the advanced glycation end-product receptor(RAGE) and cavenger receptor.These toxins interact with oxidative stress and inflammatory reactiong which jointly promote a vicious cycle,increasing damage of the cell and tissue,and participate in the occurrence of renal fibrosis.Reducing generation or blocking the biological effects of AGEs and AOPP,has become a new intervention target for delaying the progress of CKD.At the same time,because regular dialysis treatment does not clear this type of toxin,cardiovascular complications,the main cause of death in CKD is closely related with them.So it is urgent to intervene in the early stage of CRF! But there is no effective drugs for inhibition of AGEs and AOPP in clinical now.For delaying the development of CKD at present,the effec of western medicine treatment alone is still very limited.But traditonal Chinese medicine has obvious advantages in the treatment of the CKD stage2-4;which featuers as reatment determination based on sydrome differentiation and adjusting the dynamic balance of the human body,and its therapeutic effect in many multi-level and multi-element aspects is more adapted to the treatment of CRF involved with the many symptoms, and has important significance for stabling renal function and delaying the further development of renal damage.In Traditional Chinese Medicine(TCM),CRF is diagnosised as "Guan Ge","Shen Lao","Shen Feng","Long Bi","Ni Du".There are four major pathogenesis,such as:"deficiency","excess","stasis" and "toxin" in the formation of the disease.The pathogenesis of prophase and midphase of CKD is deficiency of the spleen and kidney and intermingled state of turbid phlegm and blood stasis.And the deficiency of the spleen and kidney is the root of the disease, intermingled state of turbid phlegm and blood stasis is the sign of the disease.The deficiency in origin and excess in sign are the main clinical manifestations.Yang deficiency of the spleen and kidney is more common in clinical practice,YiShen QingDu(YSQD) particles(a preparation of traditional chinese medicine)is designed to adapt to disease type,which comprise of rhubarb,monkshood,ginger,ginseng, licorice,etc.It varied from "Wen-pi-tang" which was recorded in "Qian Jin Fang".At home and abroad,a large number of pharmacological and clinical research has proven that "Wen-pi-tang" have significant treatment on CKD.The aim of this issue is to preliminarily evaluate the effect of YSQD particles on decreasing urinary toins and delaying the progression of disease for CKD which were diagnosed as Syndrome of Yang deficiency of spleen and kidney and syndrome of intermingled Turbid Phlegm and Blood Stasis in TCM,and research the mechanisms that YSQD particles delay the progression of CKD by measuring the AGEs,AOPP,CRP,GSH-Px.The details were as follows:Chartâ… Research of efficacy and salty of YSQD particles on CKD(stage3-4)- Syndrome of Yang deficiency of spleen and kidney and intermingled state of turbid phlegm and blood stasis in TCMObjective:To investigate the efficacy and safety of YSQD particles on the CKD (stage3-4,also called stage of nitremia,renal failure) which were diagnosed as Syndrome of Yang deficiency of spleen and kidney and intermingled state of turbid phlegm and blood stasis in TCM and to provide a basis for clinical applications.Methods:A randomized,double-blind,placebo-controlled parallel study was taken.48 patients(aged 18 to 65 years) with CKD stage3-4 were randomly assigned to receive placebo or YSQD particles for 8 weeks.To evaluate of the therapeutic efficacy,some indexs were used,including the 24 hours urinary protein and Blood Urea Nitrogen(BUN),Serum Creatinine(Scr),serum albumin(Alb),hemoglobin(Hb), serum Calcium(Ca²⁺),serum phosphate(P³⁺) and the efficacy(changes of Traditional Chinese medical syndrome) and side effects were assessed at the very beginning of the trials and 8th weeks later respectively.Target for the safety of blood,urine,stool occult blood add routine,liver function(ALT,AST),electrolyte(K⁺,Na⁺,Cl^-), electrocardiogram.Statistic analysis:All values are expressed as the mean±standard deviation((?)±S).Statistial analysis was performed using the statistical package SPSS for Windows Ver 13.0.Results of prior-treatment and post-treatment in the group were analyzed using paired t test.Independ two-sample t test was used for the comparion of the two groups before and after treatment.If there was heterogeneity of variance,independ two-sample t' test was used.Count data was analysed by pearsonχ² and wilcoxon W test.P＜0.05 was considered to be statistically significant.Results:1.Three cases of the experimental group shed and 21 cases included in analysis. Four cases of the control group shed,and 20 cases included in analysis.Finally 41 cases enter the analysis of results in two groups.2.After treatment of 8 weeks,the BUN,SCr decreased significantly,Hb and Alb increased distinctly in the experimental group compared with the pre-treatment (P＜0.001).Compared with the control group the above indexes were were statistically significant(P=0.043,P=0.049,P=0.047,P=0.001).The 24 hours urinary protein decreased significantly in the experimental group(P＜0.001 ),but compared with the control group,there is no significant difference between the two groups(P=0.881). The efficacy(changes of Traditional Chinese medical syndrome) compared with the control group improved significantly(P=0.001).The above indexes of the control group had no statistically significant difference before and after treatment(P＞0.05).3.The security abnormal target had no abnormalities in the two groups of patients before and after treatment.Two cases from the experimental group had diarrhea 1 day after treatment without abdominal pain,4-7 times/day.Symptoms disappeared after stopping.There were no other adverse reactions in the trial period.Conclusion: YSQD particles can significantly decrease the BUN and SCr,improve anemia and TCM symptom of CKD3-4 stages,with advantages of light side effects and high safety.Chartâ…¡Effect of the YSQD particles on the advanced glycation end products and advanced oxidation protein products in the CKD(stage3-4)Objective:To investigate the effect of the YSQD particles on the AGEs,AOPP, CRP and GSH-Px in the CKD(stage3-4) which were diagnosed as Syndrome of Yang deficiency of spleen and kidney and intermingled state of turbid phlegm and blood stasis in TCM and to research the mechanism of delay the progression of CKD.Methods:The top 20 cases in chartâ… were selected for this trial.The serum levels of the AGEs,AOPP,CRP,GSH-Px were measured by corresponding methods before and after treatment.Statistic analysis.All values are expressed as the mean±standard deviation((?)±s).Statistial analysis was performed using the statistical package SPSS for Windows Ver 13.0.Results of prior-treatment and post- treatment in the group were analyzed using paired t test.Independ two-sample t test was used for the comparion of the two groups before and after treatment.If there was heterogeneity of variance,independ two-sample t' test was used.Count data was analysed by pearsonχ² test.P＜0.05 was considered to be statistically significant.Results:1.One cases of the experimental group shed and 9 cases included in analysis. Two cases of the control group shed,and 8 cases included in analysis.Finally 17 cases enter the analysis of results in two groups.2.After treatment of 8 weeks,the blood AGEs,CRP decreased significantly, GSH-Px increased distinctly in the experimental group compare with the pre-treatment(P＜0.001,P＜0.001,P=0.002).Compare with the control group the above indexes were were statistically significant(P=0.041,P=0.018,P=0.046).The AOPP has decreased in the experimental group,but compaired with the prior-treatment in the group and the control group,there was no significant difference (P=0.133,P=0.627).The above indexes of the control group were no statistically significant difference before and after treatment(P＞0.05).Conclusion:YSQD particles can significantly decrease the levels of AGEs and CRP,increase the GSH-Px of CKD3-4 stages,and then take effect on anti-inflammatory and antioxidant and anti-fibrosis in delaying the progression of CKD.Conclusions of the whole paper:YSQD particles is the 6 types of Chinese drugs.We carried out the clinical research about YSQD particles on CKD(stage3-4) which were diagnosed as Syndrome of Yang deficiency of spleen and kidney and intermingled state of turbid phlegm and blood stasis in TCM and proved that this chinese medicine could decreased the BUN and SCr in serum,improve anemia and TCM symptom of CKD3-4 stages.Therefore YSQD particles could improve renal function and the quality of life of CKD(stage3-4).YSQD particles also can improve the renal fibrosis by decreasing the serum level of AGEs which are known as a new kind of uremic toxin-induced fibrosis.And there is mild adverse reaction and high safety.So it is an effective drug used in CKD(3-4 stage).