| BackgroundIdiopathic membranous nephropathy accounts for about 10%of primary glomerular nephritis,is a most common cause of nephrotic syndrome.About one third of patients after hormone and/or immunosuppressive therapy is still cannot achieve clinical relief,called refractory membranous nephropathy.refractory membranous nephropathy is intractable and limited efficacy,side effect is bigger,resistance is poor.Through clinical observation and experience summary,the traditional Chinese medicine treatment have a certain curative effect in refractory membranous nephropathy,and high safety.So that dig deeper into the classic theory and advantage in TCM is feasible for treatment of refactory membranous nephropathy."Qu Yu ChenCuo " method is came from "HuangDi NeiJing" for the treatment of edema,especially suitable for idiopathic membranous nephropathy edema,qi deficiency blood stasis and water wet stops inside.In inherit kidney disease expert academic experience and previous study of idiopathic membranous nephropathy,on the basis of treatment of edema in "Jin Gui Yao Lve" license",established theoretical system of "qi-blood-water" treatment of membranous nephropathy,and formed academic point by "yiqi huoxue lishui" treatment of membranous nephropathy,and has obtained the good clinical curative effect.But,the characteristics and treatment in TCM of refractory membranous nephropathyare not seen,this research probes into the TCM syndrome characteristics of refractory membranous nephropathy,summarized the clinical and pathology characteristics,and observed "Qu Yu ChenCuo" method in treatment of refractory membrane kidney disease clinical curative effect and security.Part I Study on refractory membranous nephropathy of TCM syndromes,clinical and pathological featuresObjectiveA preliminary analysis of the TCM syndrome,clinical and pathological characteristicsin refractory membranous nephropathyvs.otheridiopathic membranous membranous.MethodA single center,retrospective study was carried out in the Guang,anmenHospital,China Academy of Chinese Medical Sciences from January 2006 to December 2015.The patients with IMN confirmed by clinical pathology were observed.A total of 236 cases of IMN patients,with refractory idiopathic membranous nephropathy(RMN)58 cases,178 cases of idiopathic membranous nephropathy with non refractory.Comparate 2 groups inTCM symptoms,syndrome differentiation,general information,laboratory tests and renal pathological data,etc.,to explore the RMN of TCM syndrome,clinical and pathological characteristics.Results1 Comparison of main symptoms of TCMRMN group of top 5 common symptoms were edema(96.6%),urinary foam(89.7%)and fatigue(67.2%),nocturia(53.5%)and stool(36.2%),RMN group in edema,urine,stool,foam chest pain,nocturia performed statistical difference with non refractory IMN group(P<0.05).2 TCM syndrome differentiation2.1 Deficiency syndrome in rootRMN group and non refractory IMN group were main indeficiency in the root and excess in the branch,accounted for 96.01%vs.93.1%,no difference between the 2 groups in statistical.(P>0.05).RMN group and non refractory IMN group were main in the spleen-kidney qi deficiency,and lung-kidney qi deficiency.RMN group has 25 cases(43.1%)in spleen-kidney qi deficiency,14 cases(24.1%)in lung-kidney qi deficiency.There was no statistical difference between the 2 groups in the distribution of TCM Syndromes of deficiency syndrome(P>0.05).2.2 Excesssyndrome in branchRMN group and non refractory IMN group were main indampness syndrome and damp-heat syndrome and blood stasis syndrome.In RMN group blood stasis syndrome(89.7%),damp-heat syndrome(56.9%),dampness syndrome(39.7%),the blood stasis and damp heat syndrome had statistically difference with non refractory IMN group(P<0.05).2.3 The distribution of concurrent syndromeThere were 5 kinds of deficiency syndromeand 4 types of excesssyndrome interaction,syndrome type more,data dispersion,so merge spleen-kidney qi deficiency and spleen-kidney yang deficiency into onetype discussion.In RMNgroup has 29 cases in Spleen-kidney qi(Yang)deficiency.In the RMN group,spleen-kidneyqi(yang)deficiency was common concurrentwith dampness syndrome+blood stasis syndrome(20.7%),damp-heat syndrome + blood stasis syndrome(27.6%),damp-heat syndrome+ dampness syndrome(17.2%)and the pure blood stasis syndrome(13.8%).Concurrent syndrome in Spleenkidney qi(yang)deficiency between RMN group and non refractory IMN group has no statistically difference(P>0.05).There were no statistical differences between RMN group and non refractory IMN group in other typeof deficiency in the root and excess in the branch(P>0.05).3.Clinical features3.1 Sex,age,age of onset236 patients included in the study,135 men(57.2%)and 101 women(42.8%).In RMN group,44 cases were male(75.9%),14 cases were female(24.1%),and significant difference in statistically with non refractory IMN group(P<0.01),More men in RMN group.In the age of onset,The youngest is 21 years old,the maximum age of 83,the average age innon refractory IMN groupand RMN group was 54.18±12.83 vs.49.3±15.95 years old,there was no statistical difference between the 2 groups(P>0.05).In the age of onset,the minimum age of 17 years old,the maximum age of 78 years old,non refractory IMN group and RMN group was 48.80±12.40 vs.46±15 years,there was no statistical difference between the two groups(P>0.05).older than 55 years old patients in non refractory IMN group is 27 cases(15.2%),in RMN group of 19 cases(32.8%),there were significant differences between the 2 groups(P<0.01),the porportion of age onset older than 55 years old in RMN group was significantly higher.3.2 ComplicationIn RMN group has 37 patients(63.8%)complication Hypertension,no significant differences between non refractory IMN group(P>0.05).The highest blood pressure>180/1 10mmHg,non refractory IMN group has 27 cases(15.2%),RMN group has 10 cases(17.2%),no significant difference between the 2 groups(P>0.05).RMN group has 3 cases(5.2%)coronary heart disease,8 cases(13.8%)with arteriosclerosis,4 cases(6.8%)with thrombotic events,type 2 diabetes mellitus 8 cases(13.8%),1 cases(3.3%)with autoimmune disease,compared with non refractory IMN group,no significant difference between the 2 groups(P>0.05).2 groups of hyperuricemia,non refractory IMN group had 35 cases(19.7%),RMN group had 24cases(43.2%),there were significant differences between the 2 groups(P<0.01),RMN group combination hyperuricemia significantly more.4.Comparison of laboratory examination indexesComparison of the level of Alb,non refractory IMN group and RMN group was[25.93±6.85 vs.23.78±5.33]g/L,Alb in RMN group is relatively low,but there was no significant difference between the 2 groups(P>0.05);The comparison of Scr values,non refractory IMN group and RMN group was[69(60,80)vs.71.9(60.75,95)]umol/L,Scr in RMN group is higher than non refractory IMN,but no significant difference(P>0.05);BUN was[4.88(3.76,5.97)vs.(3.36,6.2)]mmol/L,there was no significant difference between the 2 groups(P>0.05).Estimation of glomerular filtration rate(eGFR)using the MDRD formula,the eGFR value in non refractory IMN group and RMN group was[85.46(70.67,97.72)vs.85.10(64.02105.69)]ml/min/1.73m2,no significant difference between the 2 groups(P>0.05).According to eGFR,more than 90ml/min/1.73m2,between 60-90 ml/min/1.73m2 and between 30-59 ml/min/1.73m2 were divided into 3 groups,RMN group and non refractory IMN were no statistical difference in those groups(P>0.05),but in RMN group the eGFR reduced with constituent ratio increased.In non refractory IMN group and RMN group,UA levels were[369.19 + 91.46 vs.400.45 + 97.76]umol/L,there is a statistically significant difference between the 2 groups(P<0.01),RMN group UA was significantly higher than non refractory IMN group.The level of CHO were[7.16(6.11,8.57)vs.6.7(5.74,8.80)]mmol/L,TG levels were[2.55(1.63,3.50)vs.2.13(1.73,3.49)]mmol/L,LDL levels were[4.15(3.46,5.31)vs.3.85(3.32,5.44)]mmol/L,between the 2 groups,there were no statistical difference(P>0.05).24h urinary protein non refractoryIMN group and RMN group was[3540.1 +2123.72vs.5561.9 + 2694.3]mg/24h,there were significant differences between the 2 groups(P<0.01),24h urinary proteinin RMN group was significantly higher than non refractory IMN group.Non refractory IMN group and RMN group had significantly statistically differencein 24h-UTP<3500 mg/24h,and 24h-UTP>8000 mg/24h group(P<0.01),in non refractory IMN group in the low protein group was significantly more and the RMN group,24h-UTP>8000 mg/24h group was significantly more.Urine RBC count≥10/HP in RMN group has 37 cases(63.8%),and there was no statistical difference between non refractory IMN group(P>0.05).1.5 Renal pathological data comparisonAccording to the pathological stage inrenal biopsy report,the stage between the two phases to take a higher one.There were I-MN[44.4%vs.48.3%],Ⅱ-MN[48.9%vs.43.1%],Ⅲ-MN[6.7%vs.8.6%]innon-refractory IMN group and RMN group.there was none in Ⅳ-MN,between the 2 groups showed no significant difference(P>0.05),non refractory IMN group and RMN group was no difference in pathological stage.In glomerular abnormalities,RMN group has 35 cases in glomerular mesangialcellandmatrixproliferation(60.3%),glomerulus basilar membrane thickening in 43 cases(74.1%),35 cases(60.3%)GBM vacuolar degeneration,31 cases(53.4%)has spikes projecting,10 cases(17.2%)had ischemic sclerosis,5 cases(8.6%)had crescent,12 cases(20.7%)had Global sclerosis,2 cases(3.4%)had segmental sclerosis.In renal tubular acidosis,RMN group allhadepithelial vacuolization and granular degeneration,and 43 cases had focal atrophy.In renal interstitial lesions,RMN group had no obvious lesions in 10 cases(17.2%),all above items was no significant difference with non-refractory IMN(P>0.05).In renal interstitial lesions,RMN group had 44 cases(75.9%)in renal interstitial inflammatory cell infiltration.46 cases(79.3%)had interstitial fibrosis,compared with non-refractory IMN group,there were significant differences between the 2 groups(P<0.01).In RMN group,renal interstitial lesions were more likely to be observed in cell infiltration and interstitial fibrosis.ConclusionsIn this study,refractory membranous nephropathy(RMN)of TCM syndrome,clinical pathological characteristics were summarized.The research shows that the TCM syndrome characteristics of RMN are the indeficiency in the root and excess in the branch,Qi deficiency syndrome in main,involve spleen and kidney,and the positive evidence is prominent in the blood stasis syndrome and damp heat syndrome.The clinical features of RMN were male,the age of onset was older than 55 years,the incidence of 24h-UTP was high and hyperuricemia.PART Ⅱ Research of "Qu Yu Chen Cuo"method in treatment of refractory membranous nephropathyObjectivePreliminary evaluation insafety and efficacy with"Qu Yu ChenCuo"method treatrefractory membranous nephropathy.MethodAsingle center,prospective study,was carried out in Guang’ anmen Hospital of Chinese Academy of Sciencefrom January 2015-June 2016.28 cases meet the diagnostic criteria,included in observation,using "Qu Yu ChenCuo" method of Chinese medicine treatment of 24-48 weeks,observethe changes of 24h urinary protein,TCM syndrome score,renal function,serum,albumin,and safety index between before and after treatment.Result1.General informationIn and finished the 24 weeks observation of RMN patients in 28 cases,the youngest is 21 years old,the oldest was 75 years old,the average age of 48.61±16.28 years,10 cases(35.7%)older than 55 years.In 28 patients,21 were male,7 were female,male to female ratio was 3:1.Pathological stage,I-MN in 13 cases(46.4%),II-MN in 12 cases(42.9%),III-MN in 3 cases(accounting for 10.7%).Patients with hypertension in 19 cases(67.9%),diabetes and cardiovascular disease were 4 cases(14.3%),11 cases with hyperuricemia(39.3%),2 cases of patients with thrombotic events(7.1%).2.BaselineThe baseline data of the patients in the study group were as follows:The course of disease was 3.07(2.0,3.75)years,24h-UTP was(3954.75,7009.75)mg/24h,and TCM syndrome score was 25.43±4.16.Alb was 26.46 ± 6.93g/L,in renal function,Scr 76.20±29.9umol/L,BUN 6.21(4.60,7.73)mmol/L,eGFR86,20±31.38 ml/min/1.73m2,UA 415.76±127.11umol/L.Lipids,CHO 7.04(5.81,7.66)mmol/L,TG 2.60(1.86,3.38)mmol/L?LDL 3.89±1.44mmol/L.Liver function,AST 19.58(13.10,23.25)U/L,ALT 21.21(13.25,2.45)U/L,y-GT 28.64(17.25,32)U/L.3.Comparison of main indexes before and after treatment3.1 24h-UTP24h-UTP in baseline,4 weeks,12 weeks,24 weeks,36 weeks and 48 weeks after treatment was 5664.86(3954.75,7009.75)mg/24h,5110.39 ± 2534.71mg/24h,4171.14(2397.00,5319.25)mg/24h,2990.71(1398.75,4196.00)mg/24h,2910.08(882.00,4143.00)mg/24h,1921.73(311.50,2582.00)mg/24h.Paired t-test with baseline and each time point respectively,in the 12 weeks after treatment,t=3.051,P<0.01,24h-UTP significant difference between the baseline and the 12-weeks time point,indicating that 24h-UTP has been significantly decreased.With the prolongation of treatment time,urine protein decreasedsignificantly gradually.3.2 24h-UTP remission rate24 weeks after treatment,there were a total of 28 patients,including complete remission in 0 cases,partial remission19 cases,with a total effective rate was 67.9%.36 weeks after treatment,a total of 25 patients,complete remission in 0 cases,partial remission 18 cases,with a total effective rate was 72%.48 weeks after treatment,a total of 22 patients,complete remission in 4 cases,partial remission 13 cases,the total effective rate was 77.3%.The treatment was observed in 3 time point rate had no significant difference(P>0.05),but with the prolongation of treatment time,the total effective rate is gradually increased,"Qu Yu ChenCuo" method effective treatment for RMN,but need to complete enough course of treatment..3.3 A single group ObjectivePerformanceCriteria(OPC)The target value(Po)specified in this study was a reference to CattranDC.The 24h-UTP response rate was 75%at the end of the 26 week treatment RMN with cyclosporin A.In this study,after 24 weeks treatment,the total 28cases(N=28),the number of remission in patients with(i=21),24h-UTP quantitative remission rate was 75%.P=0.599,P>0.05,there was no difference between the two treatments.The efficacyof "Qu Yu ChenCuo" method for RMN equivalent with the effect of cyclosporine A in the treatment of hormone resistance IMN.3.4 TCM syndrome scoreTCM syndrome score in baseline,4 weeks,12 weeks,24 weeks,36 weeks and 48 weeks after treatment,was 25.43±4.16,18.39±5.56,12.96±4.44,8.43(7.00,9.75),7.20±3.19,6.57±2.74.At 4 weeks after treatment,compared with the baseline,there was significant difference(P<0.01),it is believed that "Qu Yu ChenCuo" method of Chinese medicine treatment,improve symptoms.With the prolongation of treatment time,TCM syndrome score gradually reduced,symptoms improved significantly.3.5 TCM syndrome scoreimprovement rateAfter 24 week treatment,there were a total of 28 patients,there were effective 27 cases,the effective rate was 96.4%.36 weeks after treatment,a total of 25 patients,effective in 24 cases,the effective rate of 96%.48 weeks after treatment,a total of 22 patients,effective in 22 cases,the effective rate of 100%.The treatment was observed in 3 time point rate had no significant difference(P>0.05),but the overall effective rate is high,"Qu Yu ChenCuo" method of RMN Improve symptoms,significantly improved TCM syndrome score.4.Comparison of secondaryindexes before and after treatment4.1Alb、Scr、BUN、UA、eGFRCompared with the baseline and 24-weeks after treatment in Alb,renal function.Alb was 26.46±6.93 vs.33.53±8.78g/L,after treatment Alb significanthigher than baseline,there was significant difference between before and after treatment(P<0.01).Compared with the 24 week after treatment,Scr decreased and eGFR increased,but但 Scr、BUN、UA、eGFRhas no significant difference between baseline and 24-weeks treatment(P>0.05)..4.2 blood lipidsCHO,TG,LDL changes has no statistical difference between baseline and 24-weeks treatment(P>0.05).5.Safety index5.1 Blood routine,liver functionComparison of baseline and 24 weeksafter treatment of blood Hb,WBC,PLT,AST,ALT and liver function in y-GT,there were no abnormal clinical value after treatment had no statistical difference(P>0.05)." Qu Yu ChenCuo " method treat for RMN without damage to the blood system and liver function.5.2 Adverse reaction reportNo adverse reactions were reported during the study period.ConclusionsThe use ofH Qu Yu ChenCuo "method in the treatment of RMN in reducing urinary protein,serum albumin,improve clinical symptoms has obvious curative effect,and no influence on liver and kidney function,blood system,no reports of adverse reactions during the observation period." Qu Yu ChenCuo" method can be considered effecty and safetyfor RMN.It has value of clinical promotion and further research. |
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