| Diabetic mellitus (DM) is a lifelong progressive disease, usually associated with various complications in its late stage, which could cause great challenges and burdens to patients, their families, health care system and national economics. The prevalence of DM all over the world was predicts to reach7.7%by2030. The prevalence of DM in China was5.5%in2001and reached to9.7%in2008with totally92.4million diabetics. Diabetic nephropathy is one of the most common microvascular complications of diabetes mellitus, and it has become the second cause of end-stage renal disease (ESRD) in China.Up to now, there is no proved therapy to cure or prevent the progression of DKD, though some reports showed that good management of blood glucose, blood pressure and blood lipid and medicine application of Angiotensin-converting enzyme inhibitors (ACEI) or Angiotensin Receptor blockers (ARB) might postpone the disease’ progression. Traditional Chinese medicine (TCM) has been applied to treat DKD for a long history, and recently several studies have reported some advantages of TCM in ameliorating clinical symptoms, improving quality of life, decreasing urinary protein excretion and improving renal function. Nevertheless, these trials of either small sample size or lack of placebo-controlled arm or low quality monitoring and management of study process take high risk bias to these evidences to support, the effects of TCM. Therefore we undertook a prospective, multicenter, double-blind, randomized controlled study to evaluate the efficacy and safety of Chinese herbal formula (Tangshen Formula and individualized prescription based on syndrome differentiation) in treating diabetic nephropathy, which based on the investigation of the characteristics of TCM syndrome of diabetic nephropathy by means of retrospective cross-sectional survey and questionnaire survey.Objective:This study investigated the characteristics of TCM syndrome of diabetic nephropathy, and to evaluate the efficacy and safety of Chinese herbal formula (Tangshen Formula and individualized prescription based on syndrome differentiation) in treating diabetic nephropathy.Methods:Firstly, this study analyzed the characteristics of TCM syndromes of213cases of in-patients with diabetic nephropathy by using data mining methods such as cluster analysis. Secondly, this study summed up the clinic TCM experts’ experiences of the basic characteristic syndromes and symptoms of diabetic nephropathy through three series interview by questionnaires based on Delphi methods.Then,a six-center,semi-standardizedized,randomjzed,double-blind. placebo-controll ed trial was conducted to evaluate the efficacy and safety of Chinese herbal formula(Tangshen Formula and individualized prescription based on syndrome differentiation)in treating diabetie nephropathy secondary to type2diabetes mellitus.A total of180Chinese patients with DN in microalbuminuria stage and macroa]buminuria stage were randomly assigned to the Chinese herbal formula treatment group(Tangshen formula and individualized formulas based on syndrome differentiation) or the placebo group sa the ratio of2∶1,according to the method of stratified area of random,Patients were followed up for24weeks.The primary outcomes were UAER for DN patients in the microalbuminuria stage,24-hour urinary protein excretion amount for DN patients in the macroalbuminuria stage.The secondary outcomes were renal function (Scr and eGFR estimated by G/C equation);blood lipid (TG,TC,HDL-C,LDL-C);blood glycemia: seore of TCM symptoms and safety index.Standing Operating Procedure (SOP) and quality control methods were set up to guarantee quality of the process.Results:The essential characteristies of TCM syndrome of diabetic Rephropathy is deficiency in root and excess in branch.Qi and yin defieiency with blood stasis is the basic characteristies of DN in Ⅲ and Ⅳ stages sometimes accompanied with interior heat or damp-heat.with the progress of the disease,the characteristies of TCM syndrome hsa changed to deficiency of qi, blood,yin and yang;accompanied with blood stasis and damp-turbidity in stage Ⅴ.The clinie trial shows that after24weeks intervention (TSF and individualized formulas based on syndrome differentiation,along with ACEI/ARB applied sa primary drug treatment),the24h urinary protein in the treatment group was decreased(week24VS baseline,p<0.05)while the UP in the placebo group was increased (week24VS baseline,p-0.233).The change of UP between the two groups was significant (0.40±0.91g/24hr of the treatment group VS0.31±0.95g/24hr of the placebo group,p<0.05).The eGFR in the placebo group was decreased(week24VS baseline,p<0.05)while eGFR in the treatment group was improved (week24vs baseline,p=0.586).The change of eGFR between the two groups was signifieant (1.96±22.57ml/min of the treatment group VS-7.05±12.31ml/min of the placebo group,P=0.026).As lineat mised-effects model was applied to the TCm scores,the main effect of time is significant,The TCM scores of two groups were both decresaed over time,and the TCM scores of the treatment group declined significantly more than the placebo group in the24th week.There were no significant differences in partieipants Scr,blood lipid (TG、CHO、 HDL-C、 LDL-C), blood glucose (FBG), BP between the treatment group and placebo group(P>0.1). There was no significant difference of the side effects between the two groups. The herbal compound particles used in this study was well tolerated. After the end of the24weeks follow-up,80.33%subjects in the treatment group insisted on taking the medication, compared with75.86%in the placebo group.Conclusions:This study shows that TSF and individualized formulas based on syndrome differentiation, along with ACEI/ARB applied as primary drug treatment, can reduce the level of24-hour urinary protein excretion, delaying eGFR decline and improving TCM symptoms with low side effects in DN patients in the macroalbuminuria stage. Due to favorable safety, efficacy and well-tolerated, TSF would provide a candidate for treating DKD with macroabluminuria. |
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