Chinese Patent Medicines For Chronic Kidney Disease:Comparative Effectiveness Research

ObjectiveThe study aims to conduct a network meta-analysis to compare the effectiveness of different Chinese patent medicines administered to adults with chronic kidney disease(CKD).MethodsWe included randomised controlled trials(RCTs)of Chinese patent medicines,including Niaoduqing granule/capsule,Shenshuaining capsule/tablet,Cordyceps Sinensis,Haikun Shenxi capsule,Huangkui capsule,which were commonly used to patients with CKD according to the relevant literatures and clinical application.Eligible participants were adults aged 18 years old or older with CKD stages 3 to 4,regardless of sex or primary disease.Patients not requiring renal replacement therapy(RRT)in stage 5 were also included.The diagnostic criteria and stage of CKD were consistent with the standards of the Kidney Disease Improving Global Outcomes(KIDIGO).We also accepted some changes in the definition,classification of CKD in the qualified studies.On the base of conventional treatment,participants received Chinese patent medicines against each other,conventional treatment alone,or western medicine.Primary outcomes were all-cause mortality and the need for RRT.Secondary outcomes were serum creatinine(SCr),blood urea nitrogen(BUN),creatinine clearance rate(Ccr),glomerular filtration rate(GFR),24 hour urinary protein excretion,effective rate,adverse effects.Exclusion criteria included following parts:Studies in which stage of CKD,baseline GFR or serum creatinine concentration data couldn't be obtained from the article or through author contact;obvious mistakes in the literature.We retrieved the relevant literature in English and Chinese databases,as shown below:MEDLINE(Ovid SP,from 1946),Embase(Ovid SP,from 1974),the CochraneCentral Register of Controlled Trials(CENTRAL)(the Cochrane Library,Issue 2,2017),the Chinese Biomedicine Database(CBM)(from 1978),China National Knowledge Infrastructure database(CNKI)(from 1979),Wanfang Database(from 1990),Chinese Scientific Journals Database(VIP)(from 1989).The literature search was up to February 2017.After screening literatures,extracting data and assessing the methodological quality of included studies were performed.The Cochrane risk of bias assessment tool was used to assess the methodological quality of included trials.We conducted pairwise meta-analyses by synthesizing studies that compared the same interventions using a fixed or random-effect model that contained two or more studies after heterogeneity test.In pairwise meta-analysis,the I-squared test was conducted to evaluate the heterogeneity,and we conducted subgroup analyses to explore potential sources of heterogeneity.In adjusted indirect comparison,clinical and methodological similarity of eligible studies were assessed.In mixed treatment comparison,the discrepancy between direct and indirect comparison of treatments was assessed.The direct and indirect comparison of treatments were carried out by using network meta-analysis.Continuous data were presented as mean difference(MD)or standardized mean difference(SMD)with 95%confidence intervals(CIs).Dichotomous data were presented as odds ratio(OR)with 95%CI.We conducted sensitivity analysis to explore the influence of risk of bias factors.Publication biases were investigated on a funnel plot by using STATA/SE 11.0 software,which was observed whether it was symmetry.If the number of studies was less than 10 or most studies were of small sample size,we conducted Begg's test and Egger's test.STATA/SE 11.0 and WinBUGS 14.0 softwares were used to analyze data.ResultsA total of 47 Chinese literatures were included,including 3416 chronic kidney disease(CKD)stage 3-5 patients and 7 intervention measures,including Niaoduqing granule/capsule,Cordyceps Sinensis,Haikun Shenxi capsule,Shenshuaining capsule/tablet,Huangkui capsule,oral adsorbents and conventional treatment respectively.Only 6 of the included studies reported the method of random sequence generation which were randomly grouped by Excel software or the random number table.None of the studies reported allocation concealment and blinding.The results of network meta-analysis were showed as following.For the serum creatinine,Niaoduqing granule was better than Cordyceps Sinensis(MD =-20.53,95%CI[-30.39,-10.75]),Huangkui capsule(MD=-50.05,95%CI[-70.87,-29.30]),oral adsorbents(MD =-29.75,95%CI[-42.31,-17.42]),conventional treatment(MD =-61.47,95%CI[-69.25,-53.68]).Compared with Niaoduqing granule,Shenshuaining capsule/tablet(MD = 22.04,95%CI[6.91,37.43])had a better effect.There was no significant difference in the comparison between Niaoduqing granule and Haikun Shenxi capsule(MD=12.44,95%CI[-4.59,29.78]).Cordyceps Sinensis was better than Huangkui capsule(MD =-29.52,95%CI[-49.76,-9.35]),conventional treatment(MD =-40.94,95%CI[-46.86,-35.04]).Compared with Cordyceps Sinensis,Haikun Shenxi capsule(MD = 32.96,95%CI[16.57,49.50])and Shenshuaining capsule/tablet(MD = 42.57,95%CI[27.51,57.73])had a better effect.There was no significant difference in the comparison between Cordyceps Sinensis and adsorbent(MD =-9.22,95%CI[-24.65,6.10]).Haikun Shenxi capsule was better than Huangkui capsule(MD =-62.48,95%CI[-87.39,-37.68]),adsorbent(MD =-42.18,95%CI[-63.28,-21.42]),conventional treatment(MD =-73.91,95%CI[-89.45,-58.58]),but there was no significant difference in the comparison between Haikun Shenxi capsule and Shenshuaining capsule/tablet(MD=9.61,95%CI[-11.26,30.19]).Compared with Huangkui capsule,Shenshuaining capsule/tablet(MD = 72.09,95%CI[48.09,96.01])had a better effect.Oral adsorbents(MD = 20.30,95%CI[-3.60,44.27])and conventional treatment(MD=-11.42,95%CI[-30.73,7.97])showed no significant difference compared with Huangkui capsule.Shenshuaining capsule/tablet was better than adsorbent(MD=-51.79,95%CI[-69.48,-33.94])and conventional treatment(MD =-83.51,95%CI[-97.44,-69.71]).Adsorbent was better than conventional treatment(MD=-31.72,95%CI[-45.87,-17.53]).In terms of urea nitrogen,Niaoduqing granule was better than adsorbent(MD =-2.62,95%CI[-4.66,-0.64])and conventional treatment(MD =-3.47,95%CI[-4.85,-2.10]).Cordyceps Sinensis(MD=1.01,95%CI[-1.31,3.33]),Haikun Shenxi capsule(MD = 1.95,95%CI[-0.80,4.71]),Huangkui capsule(MD =-3.97,95%CI[-8.86,0.93]),Shenshuaining capsule/tablet(MD =-0.22,95%CI[-2.33,1.89])showed no significant difference compared with Niaoduqing granule.Cordyceps Sinensis was better than adsorbent(MD =-3.63,95%CI[-6.53,-0.80])and conventional treatment(MD =-4.48,95%CI[-6.37,-2.62]).Haikun Shenxi capsule(MD = 0.95,95%CI[-2.11,3.98]),Huangkui capsule(MD =-4.98,95%CI[-10.04,0.08]),Shenshuaining capsule/tablet(MD =-1.22,95%CI[-3.88,1.43])showed no significant difference compared with Cordyceps Sinensis.Haikun Shenxi capsule was better than Huangkui capsule(MD =-5.92,95%CI[-11.18,-0.66]),adsorbent(MD =-4.58,95%CI[-7.82,-1.38]),and conventional treatment(MD=-5.42,95%CI[-7.82,-3.04]).There was no significant difference in the comparison between Haikun Shenxi capsule and Shenshuaining capsule/tablet(MD=-2.17,95%CI[-5.22,0.86]).Shenshuaining capsule/tablet(MD = 3.75,95%CI[-1.30,8.83]),adsorbent(MD = 1.34,95%CI[-3.85,6.49]),conventional treatment(MD=0.50,95%CI[-4.21,5.18])showed no significant difference compared with Huangkui capsule.Shenshuaining capsule/tablet was better than adsorbent(MD =-2.41,95%CI[-4.57,-0.29])and conventional treatment(MD =-3.25,95%CI[-5.14,-1.37]).There was no significant difference in the comparison between adsorbent and conventional treatment(MD =-0.84,95%CI[-2.99,1.33]).For the creatinine clearance,4 kinds of Chinese patent medicines were compared with each other,and there was no significant difference in the comparison between Niaoduqing granule,Cordyceps Sinensis,Haikun Shenxi capsule and Shenshuaining capsule/tablet.For the glomerular filtration rate,5 kinds of Chinese patent medicines were compared each other,and there was no significant difference in the comparison between Niaoduqing granule,Cordyceps Sinensis,Haikun Shenxi capsule,Huangkui capsule and Shenshuaining capsule/tablet.For the 24 hour urinary protein excretion,5 kinds of Chinese patent medicines were compared each other,including Niaoduqing granule,Cordyceps Sinensis,Haikun Shenxi capsule,Huangkui capsule and Shenshuaining capsule/tablet.Compared with Niaoduqing granule,Cordyceps Sinensis(MD = 0.51,95%CI[0.04,0.97])had a better effect.Cordyceps Sinensis was better than Shenshuaining capsule/tablet(MD =-0.19,95%CI[-0.32,-0.07]),and there was no significant difference between the other Chinese patent medicines.For the effective rate,there was no significant difference in the comparison between Niaoduqing granule,Cordyceps Sinensis,Haikun Shenxi capsule,and Shenshuaining capsule/tablet.The sequence of effective according to probability was as below:For the serum creatinine,the top three were Shenshuaining capsule/tablet(1.181),Haikun Shenxi capsule(1.898),Niaoduqing granule(2.921).For the urea nitrogen,the top three were Haikun Shenxi capsule(1.441),Cordyceps Sinensis(2.135),Niaoduqing granule(3.208).For the creatinine clearance,the top three were Haikun Shenxi capsule(1.813),Niaoduqing granule(2.579),and Cordyceps Sinensis(2.696).For the glomerular filtration rate,the top three were Cordyceps Sinensis(1.754),Haikun Shenxi capsule(2.642),and Huangkui capsule(3.222).For the 24 hour urinary protein excretion,the top three were Cordyceps Sinensis(1.817),Huangkui capsule(1.830),Haikun Shenxi capsule(2.704).For the effective rate,the top three were Shenshuaining capsule/tablet(1.954),Niaoduqing granule(2.557),and Haikun Shenxi capsule(2.718).ConclusionsSome of Chinese patent medicines combined with conventional therapy are superior to conventional therapy alone for chronic kidney disease in lowering serum creatinine and urea nitrogen.They also have more effect in the terms of creatinine clearance,GFR,24 hour urinary protein excretion and the effective rate.Each drug has its merit in treatment of chronic kidney disease,but Haikun Shenxi capsule,Niaoduqing granule,and Cordyceps Sinensis are better than other Chinese patent medicines.Because of the paucity of literature and lower methodological quality,the conclusion need further validation.