Evidence-based Evaluation Of Traditional Chinese Medicine Intervention For Chronic Kidney Disease Based On Literature And Clinical Dat

Background:The prevalence of chronic kidney disease(CKD)is increasing year by year.A certain number of CKD TCM clinical practice guidelines have been published in China,but there are no studies to evaluate the methodological quality,reporting quality,applicability,and clinical implementation level of these guidelines.The internal medicines recommended in the guideline include traditional Chinese medicine prescriptions and proprietary Chinese medicines,but the former is often derived from theoretical derivation and expert consensus,and the level of evidence and specific improved outcome indicators are not clear;although the latter has efficacy trials before and after the market,but The differences and ranking of curative effects among different varieties still need to be further studied.Further,as an important form of evidence transformation,the clinical practice of the guideline and its prescription efficacy research results also needs to be evaluated and fed back.Objective:From the perspective of guidelines and randomized controlled trials,to summarize the advantages and effects of traditional Chinese medicine in CKD intervention,and to evaluate the transformation and implementation level of relevant evidence and recommendations through empirical research.Methods:Study 1:Evaluation of methodological quality and reporting quality of TCM clinical practice guidelines for CKDSearch SinoMed,CNKI,VIP,Wanfang and other literature libraries to obtain CKD Chinese medicine/integrated Chinese and Western medicine clinical guidelines as of February 2021,and qualitatively analyze the name,year,formulation unit,formulation method and other characteristics of the included guideline after screening,and extract diagnostic criteria,syndrome type,treatment method,decoction prescription and composition,Chinese patent medicine advice,other core elements such as therapy.After verifying the consistency,4 investigators independently used the AGREE II manual,the RIGHT list and the TCM clinical practice guideline applicability evaluation recommendation list to evaluate the methodological quality,reporting standards and clinical applicability of the guidelines.SPSS26.0 was used for analysis.Study 2:Systematic review and methodological evaluation of randomized controlled trials of traditional Chinese medicine classic prescriptions in the treatment of CKDThis study was designed and conducted according to the Cochrane Handbook for Systematic Reviews of Interventions.PubMed,Cochrane Library,Embase,Web of science\SinoMed,CNKI,VIP,Wanfang and other literature libraries were searched,and the literature was screened.The type of included studies was randomized controlled trials.The research objects were CKD patients;the intervention measures in the experimental group were Jingfang Shifang orally or combined with conventional treatment;the interventions in the control group were:placebo and conventional treatment.The main outcome measures were:quality of life scale,end points such as kidney transplantation,the number of hospitalizations during the follow-up period,and the incidence of adverse events.Secondary outcome measures were:eGFR,Scr,24hUpro,BUN,Ccr,ACR,AER,Hb.Exploratory outcome indicators:blood P,blood Ca,iPTH;TP,Alb,PA,TRF,SGA;VEGF,hs-CRP,IL-6,TNF-α;CD3,CD4,CD4/CD8;Risk of bias assessment,qualitative and quantitative analysis of data.Study 3:Evaluation of clinical efficacy of traditional Chinese medicine in the treatment of CKD(non-dialysis)based on Bayesian network meta-analysisComplete the Chinese and English database search(limited to core journal publications),and screen the literature.The type of included study was a randomized controlled trial;the research subjects were non-dialysis CKD patients;the intervention measures in the experimental group were one or two Chinese patent medicines(Niaoduqing Granules,Shenshuining Capsules/tablets,Jinshuibao Capsules,Bailing Capsules,Haikou)Kunshenxi Capsules,Huangkui Capsules,Yishen Huashi Granules,Shenyan Kangfu Tablets,Compound Shenyan Tablets,Tripterygium Polyglycosides Tablets,Kangshen Granules,Shenfukang Capsules,Shenyanshu Tablets)combined with conventional treatment;interventions in the control group For conventional treatment or another traditional Chinese medicine combined with conventional treatment.Outcomes were:24hUpro,eGFR,Ccr,Scr,BUN,Hb,Alb,and incidence of adverse events.RevMan 5.3 was used for literature quality evaluation;Stata 13.0 was used to draw network evidence map,GeMTC software was used to perform network Meta analysis based on Bayesian framework,and probability maps were drawn and ranked by probability;Markov chain-Monte Carlo(Markov Chain-Monte Carlo)was used Chain Monte Carlo,MCMC)random effects model,4 chains are simulated,the initial value is set to 2.5,the step size is 10,the first 20,000 iterations are set for annealing,and the last 50,000 are used for sampling.Study 4:Evaluation of clinical practice of TCM intervention in CKD based on clinical audit and questionnaire surveyOn the basis of studies 1 to 3,retrospectively inspected inpatient medical records containing"CKD" in the diagnosis of nephrology department of a tertiary Chinese medicine hospital in Beijing,and extracted Chinese and Western medicine diagnosis,staging,syndrome differentiation,legislation,prescription,external treatment,nursing and Discharge efficacy indicators and other information,especially the use of traditional Chinese medicine prescriptions and proprietary Chinese medicines.According to the degree of compliance of the observed medical records with the guidelines,the clinical practice was analyzed according to the percentage scoring standard(>80%for compliance,60%-80%for moderate compliance,40%-59%for general compliance,<40%for non-compliance)The degree of application of evidence-based evidence in China;at the same time,the snowball sampling method was used to calculate the maximum sample size(95%confidence level)required under the 6%error degree,using the form of electronic questionnaire for the front-line clinicians in the domestic Chinese medicine nephrology department.The main basis for the treatment of CKD syndrome differentiation and legislative prescriptions,the cognition and application of relevant guidelines,the selection of traditional Chinese medicine prescriptions and proprietary Chinese medicines,their views on the problems of the current guidelines and the demand for the content of the guidelines were investigated.Results:Study 1:19 relevant guidelines were included.Among them,1 each for "Guange"and "edema";3 each for "IgA nephropathy" and "chronic renal failure",2 each for "chronic glomerulonephritis","chronic pyelonephritis" and "diabetic nephropathy",Lupus nephritis","CKD","uric acid nephropathy","primary nephrotic syndrome",and "allergic purpura nephritis" each;16 are formulated by the national first-level society,and 1 is an updated and revised version,4 parts were formulated using evidence-based medicine methods,8 guides mentioned the funding of scientific research funds;the promulgation year spanned from 2008 to 2020,and 3 were formulated within the past 5 years;involving 26 traditional Chinese medicines such as "drowning poisoning" and "edema" Disease categories;a total of 66 types of syndrome expressions,with high frequency including "liver and kidney yin deficiency","qi and yin deficiency",etc.;a total of 80 classic prescriptions are recommended,with high frequency including Taohong Siwu Decoction,Zhenwu Decoction,etc.;14 guidelines recommend a total of 67 kinds of proprietary Chinese medicines,among which Huangkui Capsules and Nephritis Rehabilitation Tablets are more frequently used.14 guidelines recommended unilateral prescriptions,enema,diet therapy and other treatment methods;the overall scores of AGREE Ⅱ in 19 guidelines were all low,the clarity of expression(52.63%),the scope and purpose(42.4%),the participants(24.27%)%),development rigor(19.19%),editorial independence(18.42%),and applicability(7.24%),only 5(26.31%)guidelines were"recommended" by reviewers;The total reporting rate of each item was between 14.29%and 74.29%,and the average reporting rate was(24.36%±17.15%).Among them,basic information(54.39%),background(34.87%),evidence(12.63%),and recommendation(17.29%)%),review and quality assurance(10.52%),funding and conflict of interest declaration and management(26.32%),other aspects(31.58%);the general report of the 19 guidelines for the applicability evaluation of Chinese medicine clinical practice guidelines for the recommended list of applicable items The reporting rate was between 34.09%and 71.43%,the average reporting rate was(47.5±11.49)%,and the report quality and applicability evaluation scores were low.Study 2:11,725 articles were retrieved,and 80 randomized controlled trials with a total of 5,584 patients were finally included.A total of 52 classic prescriptions were included in the intervention.The results of qualitative and meta-analysis found that the addition of Guipi Tang(13.96[12.12,15.80])improved the quality of life,and the addition of Liujunzi Decoction(5.02[0.53,9.51])compared with CKD patients who only received conventional treatment.)and other 4 classic recipes are improving the glomerular filtration rate,adding 4 classic recipes including Rhubarb Aconite Xixin Decoction(7.27[4.79,9.75])are improving endogenous creatinine clearance rate,adding Fangji Huangqi Decoction(n=292 people,14-60 days of treatment,MD:-13.72,95%CI:-20.42 to-7.03,P<0.01,I2=92%)and other 11 classic prescriptions are reducing serum creatinine,plus warming the spleen Decoction(-9.93[-10.30,-9.56])and other 11 classic prescriptions were used to reduce blood urea nitrogen,and Liuwei Dihuang decoction(n=128 people,30 days of treatment,MD:-574.05,95%CI:-769.09 to 379.01,P<0.01,I2=3%)and other 15 classic prescriptions had statistically significant differences in reducing urinary protein,suggesting that there is a certain curative effect.In addition,most of the differences between the traditional Chinese medicine classic prescription and the control group were statistically significant in improving the nutritional status of patients,calcium and phosphorus metabolism,inhibiting inflammatory factors,and improving immune indicators.In terms of safety,9 studies reported 47 adverse reactions in the experimental group and 106 adverse reactions in the control group,and the results of the two groups were statistically significant.The symmetry of the inverted funnel plot was poor,suggesting that there may be a certain degree of risk of publication bias.In this study,there were 52 traditional Chinese medicine prescriptions whose efficacy was verified,accounting for 65.00%.of the total number of prescriptions(80)recommended by the guideline in the first study.Study 3:3106 literatures were retrieved,and 167 RCTs were finally included,with a total of 16193 patients.There were more RCTs of Niaoduqing Granules(45 items)and Bailing Capsules(23 items)combined with conventional treatment than conventional treatment;there were 11 head-to-head RCTs.In terms of efficacy evaluation,101 RCTs reported the outcome of 24-hour urinary protein,including 20 prescriptions of Chinese patent medicines.The network meta-analysis yielded 210 pairwise comparisons,of which 44 comparisons,including Bailing+Tripterygium+CT and CT(-1.06[-1.81,-0.32]),were statistically significant.Rank from high to low(top 3):Bailing+Tripterygium+CT>Tripterygium+Compound Nephritis+ CT>Bailing+Shenfukang+ CT;25 RCTs reported the outcome indicators of eGFR,including 10 A Chinese patent medicine prescription.The network meta-analysis generated 55 pairwise comparisons,of which the difference between CT and Shenfukang+CT(-14.26[-25.96,-2.50])was statistically significant.Rank from high to low(top 3):Shenfukang+CT>Haikun Shenxi+ Jinshuibao+CT>Shenshuining+CT;38 RCTs reported the outcome of Ccr,including 9 proprietary Chinese medicines Prescription,network meta-analysis generated 45 pairwise comparisons,of which the difference between CT and Shenyanshu+CT(-30.96[-40.65,-20.85])was statistically significant among 13 comparisons.Rank from high to low(top 3):Shenyanshu+CT>Jinshuibao+CT>Niaoduqing+CT;156 RCTs reported the outcome indicators of Scr,including 20 kinds of proprietary Chinese medicine prescriptions,generated by network meta-analysis There were 190 pairwise comparisons,among which the differences between CT and Haikun Shenxi+CT(80.93[52.73,112.14])were statistically significant.Rank from high to low(top 3):Haikun Shenxi+CT>Tripterygium + Jinshuibao+CT>Shenshuining+CT;142 RCTs reported the outcome indicators of Bun,including 18 kinds of proprietary Chinese medicine prescriptions,the network meta-analysis generated 190 pairwise comparisons,of which the difference between CT and 15 comparisons including Haikun Shenxi+Jinshuibao+CT(8.27[0.70,15.53])was statistically significant.Rank from high to low(top 3):Haikun Shenxi+Jinshuibao+CT>Bailing+Shenfukang+CT>Yishen Huashi+CT;24 RCTs reported the outcome indicators of Hb,including For 8 proprietary Chinese medicine prescriptions,the network meta-analysis yielded 36 pairwise comparisons,of which all the differences among the comparisons were not statistically significant.Rank from high to low(top 3):Jinshuibao+CT>Yishenhuashi+CT>Huangkui+CT=Shenshuining+CT;39 RCTs reported the outcome of Alb,including 13 middle For over-the-counter prescriptions,the network meta-analysis generated 91 pairwise comparisons,of which the differences between CT and 24 comparisons such as Tripterygium wilfordii+Jinshuibao+CT(-18.81[-24.76,-12.89])were statistically significant,and the Rank was determined by The order from high to low(top 3)is:Tripterygium wilfordii + Jinshuibao+CT>Shenfukang+CT>Tripterygium wilfordii+CT.60 studies reported the specific situation and number of adverse reactions,and the difference between the two groups was not statistically significant.The results of the node splitting method showed that among the 5 outcome indicators forming a closed loop,there was no significant difference between the direct comparison and the indirect comparison of every 2 intervention measures(P>0.05);all network Meta-analysis model tests were 1.00≤PSRF≤1.05;The inconsistency test and convergence test were good;the funnel plot was not symmetrical,suggesting that there may be some publication bias.Study 4:A total of 640 inpatient medical records were collected in the clinical audit section.The TCM disease diagnosis coincidence rate was only 2.81%;involving 84 syndrome types,more than half of the syndrome types in the medical records were completely inconsistent with the guideline syndrome types(355 cases,55.47%),and only 22.03%fully met;102 cases(16.45%)medical records indicate the source of the prescriptions used,including 66 prescriptions,of which 5 are recommended prescriptions in the "Guidelines for the Diagnosis and Treatment of Chronic Renal Failure with Integrated Traditional Chinese and Western Medicine(2015)",accounting for the ratio of the total prescriptions recommended in the guideline 71.43%(5/7),accounting for only 10.22%of the prescriptions in this inspection;10 prescriptions are recommended in the "Guidelines for the Diagnosis and Treatment of Common Diseases in Traditional Chinese Medicine(Traditional Chinese Medicine Diseases and Syndromes)",accounting for The ratio of total prescriptions was 50.00%(10/20);it accounted for 23.35%of the prescriptions in this audit;there were 16 effective prescriptions in the second study,accounting for 50.36%of the prescriptions in this audit;Chinese patent medicines,Shenkang Injection was the most frequently prescribed(271 cases,42.34%),and Haikun Shenxi Capsule was the most frequently prescribed oral(103 cases,16.09%).There are no prescription records for 6 Chinese patent medicines,including Shenhuashi Granules,Kangshen,Shenfukang Capsules,and Fufang Shenyan Tablets.In the questionnaire survey part,75 questionnaires were issued and returned,and the effective rate was 100%.In response to the question of "the main basis for legislative prescriptions based on syndrome differentiation in the treatment of CKD",most physicians choose to follow "experience from teachers"(74.67%),followed by "ancient classics and prescriptions"(53.77%)and "guideline recommendations"(50.6 7%);In terms of cognition and application,according to a gradient of 0 to 10,the scores of the three recent guidelines are:4.56,4.59,and 4.69;among the traditional Chinese medicine prescriptions recommended by the guideline in study 1 and the effective conclusions drawn in study 2,five Lingsan(class)(64.00%),Zhenwu Decoction(class)(60.00%),Liuwei Dihuang Decoction(class)(57.33%)were chosen more;Chinese patent medicines recommended by the guideline in Study 1 and effective conclusions in Study 3 Among them,Bailing(65.33%),Jinshuibao(58.67%),Huangkui(53.33%)and Niaoduqing(52.00%)were chosen more.Regarding the current guidelines,the most physicians(45.33%)believed that there was a problem of "lack of high-quality original research evidence",followed by "insufficient promotion and publicity"(44.00%).For future guidelines,the most physicians(57.33%)are the "standards of syndrome differentiation" and "experience of famous doctors and prescriptions",followed by "specific prescriptions of traditional Chinese medicines/proprietary Chinese medicines"(49.33%).Conclusion:Judging from the current literature and clinical data samples,there is a certain disconnection in the evidence-based transformation path of "(practice)experience-evidencerecommendation-practice(experience)" for Chinese medicine intervention in CKD.From the clinical data,the diagnosis and treatment needs and practice scope of traditional Chinese medicine intervention in CKD are expanding.,the practice experience of diagnosis and treatment has not been promoted to "evidence" through scientific verification(such as RCT).Judging from the comprehensive results of the evidence,the classical Chinese medicine prescriptions and proprietary Chinese medicines have certain curative effects in protecting residual renal function,delaying the progression of renal failure,inhibiting inflammation,improving nutritional status,and preventing complications,and are relatively safe.However,due to the methodology of the study itself Due to quality limitations,large heterogeneity,etc.,coupled with the methodological "inadequate evidence-based and more than consensus" in the guideline formulation process,the evidence from clinical studies has not been fully transformed into recommendations.In the practice of diagnosis and treatment,the recommendations in the guidelines often cannot be fully implemented and applied in the real world due to the low level of original research evidence,poor reporting quality and applicability of the guidelines themselves,poor promotion,and inability to solve clinical problems.,and effectively play the role of guiding clinical practice.At the same time,it should be noted that even when the evidence-based strength of the guideline recommendations is low,the clinical research evidence is relatively loose,and the methodological quality needs to be improved,it can still be observed that the traditional Chinese medicine intervention in CKD is in the "experience-evidence-recommendation opinion" There is a certain degree of theoretical fit between them,which is mainly related to the system of theory,law and prescription of traditional Chinese medicine,which shows that under the guidance of traditional Chinese medicine theory,evidence-based medicine methods can be fully used to further refine and summarize the characteristics and advantages of traditional Chinese medicine intervention in CKD diagnosis and treatment,to further practice and explore the evidence-based medical model of traditional Chinese medicine to intervene in the clinical diagnosis and treatment of CKD.