| BackgroundRefractory nephrotic syndrome (Refractory nephritic syndrome, RNS) refers to the primary nephrotic syndrome (primary nephrotic syndrome, PNS) which have been treated with Standard doses of hormones, but it has been steroid-dependent nephrotic syndronme(SDNS), frequent relapse nephrotic syndrome(FRNS), steroid-resistant nephrotic syndronme(SRNS) and partial effect. SDNS refers to reducing or stopping hormone in2weeks. steroid partial effect is reduction in proteinuria after standard hormone therapy, but24h protein≥2g/1.73m2. FRNS is the PNS which remission within half year recurrence more than2,1year more than3times after standard dose hormone therapy. SRNS has been usede of standard doses of prednisone therapy12weeks, without reducing urinary protein, or decreasing but still not gettde rid of nephrotic syndrome (nephrotic syndrome, NS). Focal segmental glomerular sclerosis, should be used hormone therapy more than16weeks but invalid, can consider hormone resistance.For NS,Western medicine treatment of PNS preferred glucocorticoids, but for RNS, it often needs to combine with other immunosuppressive agents.in the clinical, Cyclophosphamide (CTX),nitrogen mustard (chlorophyll), ring spore factor A (CsA) delayed kidney damage of some patients, postponed the time of end-stage renal disease(ESRD), but the immune inhibitors have more serious adverse reactions than hormones, such as renal toxicity and toxic liver damage, high blood pressure, blood glucose, gonad inhibiting (especially in men), bone marrow suppression and hemorrhagic cystitis, etc. New immunosuppressant for Mycophenolate Mofetil (MMF), leflunomide(LEF) and tacrolimus (TAC), have smaller side effects, low recurrence rate, and can more effectively reduce the urine protein, and more and more been payed attention to, but their price is mor expensive, so bring heavyer burdenthe to society and the family. Now the results of the study relate to the evidence-based medicine (evidence-based medicine, EBM) about new immune inhibitors are still few, remain to be further practice summary.In general, western medicine treatment of RNS are mainly high quality low protein, low salt diet, inducing diuresis to reduce edema, reducing urinary protein, and inhibiting renal immune and inflammatory response, yet no drug can completely block the progress of RNS.The Traditional Chinese Medicine (TCM) pay more attention to holistic concept and treatment based on different syndrome in treating RNS, so shows the character of the schools of thought contend. Healers of stage theory treat it with releasing lungs and water in edema syndrome and using ephedra forsythia rice bean soup and wupi drink to add or subtract, clear heat and water use longdan xiegan decoction, attack water with shuzuo drink. Daoshui fuling decoction is used in promoting qi circulation to induce diuresis. Bolus of cassia twig tuckahoe and wupi drink are used in removing stasis and alleviating water retention. Invigorating spleen for diuresis use huangqi decoction and wupi drink. Nourishing yin clearing damp use grifola tonga taste, Warming yangand diuretic use zhenwu decoction and wupi drink. To regulating spleen and stomach is important in edema subsided period, which use shengling baishu powder. Invigorating the kidney and improving blood circulation use erxian decoction. Regulating Du and Ren channel use guilu erxianjiao.According to the traditional syndrome differentiation and treatment variation,the deficiency of spleen and kidney is basic, but other viscera, hot and humid are secondary. Advocate to use the method of tri-jiao syndrome differentiation in treatment of RNS. According to the dosage of hormone at different stages, someone thinksthat using large dosage of hormone often appear internal Yin deficiency or dampness and heat, if prescriptions which can nourish Yin, send fire or dispersedampness be given, they can reduce untoward effect; the TCM which warm spleen and kidney often can reduce illness relapse and consolidate curative effect in the process of reducing the hormones. Some doctors treat RNS with specially designed prescriptions. All in all, not only the TCM has exact curative effect in delaying the exacerbation of RNS, but also improve the patients’ symptoms and reducethe adverse effects of corticosteroids and immunosuppressant.Though the TCM has exact curative effect, the methods of treatments are various. generally it can be divided into5classes:1. The staging treatment;2. Treatment variation based on syndrome differentiation;3. the specially designed prescription;4. According to the dosage of hormone at different stages, then carry out treatment variation based on syndrome differentiation;5. Combining TCM and western medicine treatment. Therefore, according to the theory of TCM and using advantages and characteristics of treating RNS, actively exploring effective agent for the treatment of RNS in TCM, which are very important to prevent or delay the development to ESRD. Shenkang pills are hospital preparation, and treat RNS several years in the clinical,so its curative effect is certain extent, and can delay the exacerbation of RNS. Hence, this subject aims to preliminarily evaluate the effect and the safety of shengkang pills in treating RNS, and provide practical basis for its clinical application.Objective1.Preliminaryly evaluate the clinical curative effect of shenkang pills in treating RNS.2.preliminarily evaluate the safety of shengkang pills in treating RNSMethod1Experimental design:randomized, controlled clinical trial program.2Clinical resources:Observational cases were inpatient and outpatient patients in the center of kidney disease which combines traditional Chinese and western medicine in zhujiang hospital of southern medical university in June2012to August2012. Using random numbers table, each30cases of control group (western medicine foundation treatment) and30cases of experimental group (taking shenkang pills on the basis of the control group).3Treatment methods:All of the patients adopt based western medicine therapy that high quality low protein (0.6-0.8g/(kg), d) and low salt (<3g/d), and prednisone (lmg/(k·d)) for8-16weeks, including cyclophosphamide (CTX) which is chaintravenous and used with lg/month(total150mg/kg), ACEI/ARB which is peroral.Reducing urinary protein, diuresis, anti-infection, anticoagulation, correcting water, electrolyte disorder and other symptomatic treatment were given according to the condition. Experimental group were given shenkang pills(1pill (6g) each time,2times a day) on the basis of western medicine treatment. Treatment for3months. Its basic component is astragalus mongholicus, Gordon euryale seed, Cherokee rose, leech, motherwort, corn stigma, etc. It has been as a hospital preparations (preparation document number:total league system:2000FP12001), and used several years in the clinical treatment of patients with RNS, and curative effect. It also has obtained national invention patent (the composition of shenkang pills and research of its craft, patent number ZL200610036515.2).4Examination contents4.1The primary efficacy evaluation index:24hours urine protein quantity4.2The secondary efficacy index:plasma albumin determination, blood lipids (total cholesterol, glycerin three greases, high density lipoprotein, low density lipoprotein), coagulation/fibrinolysis (fibrinogen, D-two dimers, thrombin time, kaolin partial thromboplastin time) and TCM efficacy.4.3Safety of treatmentRoutine blood routine, routine urine, dung urine+occult blood, electrolytes, liver function, urinary tract ultrasound, ecg and adverse events.5Examination criteria of therapy effects5.124hour urine protein quantitative efficacy evaluation:(1)Valid effect:urine protein quantitative<0.20g/24h, determined to complete remission;(2)effect:urine protein quantitative0.2-3.5g/24h or baseline decrease is greater than or equal to50%, judged to be partially effective;(3)invalid effect:urine protein quantity is greater than or equal to3.5g/24h, decision invalid.5.2TCM efficacy evaluation(1)clinical cure:clinical symptoms, physical signs disappeared, TCM total score than before treatment decreased more than95%. Valid effect:clinical symptoms, signs were improved, TCM total score than before treatment decreased more than70%,<95%.(2)Effect:clinical symptoms, signs have improved, TCM total score than before treatment decreased more than30%,<70%.(3)Invalid effect:clinical symptoms, signs were not obvious change for the better, or even aggravate, TCM total score than before treatment decreased<30%.Note:formula (nimo method) to:[(before points-points after treatment)÷before points] x100%.6Statistic analysis:All values are expressed as the mean±tandard deviation(x±s). Statistial analysis was performed using the statistical package SPSS for Windows Ver13.0. 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. Count data was analysed by pearson x2and wilcoxon W test. P<0.05was considered to be statistically significant.Results1Comparison of the main curative effect:24hupr is the main curative effect evaluation indexes, and24hUpr of experimental group are significant difference (P=0.000) before and after the treatment. Comparison had significant difference (P=0.002) between the two groups after treatment.18cases of experimental group had marked effect,10cases were effective, but2cases are ineffective;9cases of control group were markedly effective,10cases were effective, but11cases were invalid. Comparison between the two groups have significant difference (Z=2.866, P=2.866).2Comparison of secondary efficacy2.1Comparison of TCM symptoms curative effect before and after treatment in the two groups:based on evaluation standard of TCM symptoms curative effect,it has statistically significant difference (Z=-4.980, P=0.000) between the experimental group and control group, and suggests that shenkang pills can effectively improve the patients’TCM syndrome.2.2Comparison of blood lipid before and after the treatment between two groups: the changes of Alb, Chol and TG are significant difference (P=0.000, Paired Samples T Test) in experimental group after the treatment. Alb and Chol of the control group were statistically significant (P<0.05) before and after treatment,but TG is no statistical significance (P=0.315). Comparison had significant difference (PAIb=0.001, PChoi=0.000, PTG=0.000, Independent Samples T Test) between the two groups after treatment. The result shows that the treatment group is better than control group in terms of reducing blood lipids and improving Alb.2.3Comparison of two groups in blood coagulation/fibrinolysis indexes before and after treatment:comparison of the two groups before and after treatment (Paired Samples T Test):the FG, D-D, APTT and TT of the experimental group have significant difference (P=0.000); FG, D-D and APTT of control group after treatment was statistically significant (P<0.05), while the TT has no statistical significance (P=0.055). Comparison between the two groups after treatment (Independent Samples T Test):it has statistically significant (P<0.05) and suggests that anticoagulation in experimental group were better than the control group.3Comparison of safety indicators before and after treatment3.1Comparison of liver and kidney function in two groups before and after treatment:BUN was statistically significant (P=0.01) in treatment group after treating, while the control group has no significant difference (P>0.05); Scr, ALT and AST changes have no statistical significance (P>0.05). Compared between the two groups after treatment, the change of BUN have significant difference (P=0.003), Scr, ALT and AST, have no significant difference (P>0.05).3.2Comparison of other security index before and after treatment:RBC, Hb, WBC and PLT were not significant difference (P>0.05) in both two groups before and after treatment. Comparison between the two groups after treatment:RBC, Hb and PLT was not significant difference (P>0.05), but the change of WBC was significant (P=0.041). Stool routine, electrocardiogram and urinary tract ultrasound were not significant difference (P>0.05) in the two groups before and after treatment.4Drug side effects were observed Cushing syndrome, gastrointestinal tract reaction,liver and kidney dysfunction,upper respiratory tract infection and other side effects appeared in the process of treatment. The incidence of the side effects of treatment group was50.0%, the incidence of adverse events was76.6%in control group. Incidence of adverse reactions of treatment group were significantly lower (chi-square=4.593,P=0.032) than the control group.ConclusionsShenkang pills combined with based western medicine therapy can significantly reduce the24hUpr, elevate Alb, and improve the main clinical symptoms. Curative effect of Shenkang pills is positive. To a certain extent, it can delay the exacerbation of the RNS and be superior to pure western medicine treatment. It also can improve high coagulation state, reduce blood fat and significantly reduce the adverse reaction of the hormone and immune inhibitors. Foundation was laid for further evaluating clinical curative effect of it. |
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