The Research Of The Clinical Curative Effect About LiuWei And Guifu Dihuang Pill To The Third Phase Of Diabetic Nephropathy

ObjectiveDiabetic nephropathy(DN) is the most important and common complication of diabetes mellitus(DM), which is the main leading cause of death in patients with diabetes. According to Mogensen method, the criteria for diagnosis of DN Ⅲ period as a persistent microalbuminuria, which means two times24-hour urinary albumin excretion rates trace from20to200ug/min (30-300mg/24h) within6months. Early DN will develop for renal failure in5～10years without any intervention. Therefore, it is important to diagnosis and treatment DN early, once in clinical proteinuria period, renal damage is difficult to reverse. Western medicine treatment for DN at present except to control blood sugar, lower blood pressure.lowering blood fat, blood coagulation resistance, there is no other special useful way. In recent years, the research of traditional Chinese medicine take more and more attention in DN treatment, modern research shows that TCM can effectively reduce albuminuria, delay the progress of kidney function and protect the development of DN.So far the problems of treatment of traditional Chinese and western medicine exist in the following:1, Quite a number of solutions is the doctor’s clinical experience, which are strongly and subject, not through a scientific decision-making RCT test.2, Although a few number of solutions take RCT test, but there are no strict random, lack of effective positive control problems, so the effectiveness of the proposed solutions are limited.Therefore, this research hope to infer a better solution through the large sample analysis of literature, META-analysis and expert questionnaire survey, and test its efficacy and safety to the third phase of diabetic nephropathy through the standard clinical trials,for the purpose of further regulating and guidance of traditional Chinese and western medicine treatment of the third phase of diabetic nephropathy.Methods1, the literature investigationSearch the following database:VIP(1989～2009),Medline(1979～2009), Wanfang full-text database(1982～2009),CBM disc (1990～2009) and CMA digital periodicals(1994-2009)and reference lists of all papers identified also were checked. Literature between1984-2009were choosen and all the data were analysised by SPSS13.0software. The total of2300articles are searched,from these literature, screening out223references of TCM/Chinese and western medicine clinical treatment for the third phase of diabetic nephropathy, using SPSS13.0software to make the metrology and cluster analysis, in order to find out the common traditional Chinese medicine and medicine couple.2, expert questionnaire surveyMaking half closed, fill type questionnaire according to the literature statistics results, doing questionnaire survey by registered mail. After questionnaire recovery, using SPSS13.0software to make the metrology analysis, to summed up the best treatment by statisting common symptoms, type, and prescriptions for the third phase of diabetic nephropathy.3, META-analysisAccording to the literature investigation and expert questionnaire results, choose Liuwei dihuang pill and Guifu dihuang pill for best traditional Chinese medicine treatment of the third phase of diabetic nephropathy.The domestic documents and literatures of randomized controlled about the third phase of diabetic nephropathy using Liuwei dihuang pill/soup or Guifu dihuang pill or Jinkui shenqi pill were retrieved and systematically evaluated. The qualities of all literatures were assessed according to JADA scale. All data were analyzed using Revman4.2software.4, Clinical randomized trialsAccording to the literature investigation, expert questionnaire survey and META-analysis results, with a final determination to optimization scheme characted by ACEI/ARB joint LiuWei/Guifu dihuang pill for the third phase of diabetic nephropathy. Using a multicenter, randomized, open, parallel, positive control, superior effect sex verification clinical trials, to evaluate the efficacy and safety of the scheme to the the third phase of diabetic nephropathy.Results1, Literature analysis results for research directionA total of2300articles were choosen,196of them involved clinical experience or cases,53of them involved study of etiology and pathogenesis,58of them involved treatment based on syndrome differentiation,117of them involved different sorts of TCM treatment,613of them involved make-up and standard treatments,563of them involved patent chinese medicine and single chinese medicine,700of them involved treatments contain both traditional Chinese medicine and ACEI/ARB2300articles contained1721RCT article (63%), JADA score to all the literature, there are180paper get0points (10.46%),1393article get1points (80.94%),23article get2points (1.34%),105paper get3points (6.10%),13article get4minutes (0.76%), five articles get5points (0.29%), ang2paper get6points (0.11%), high quality RCT research is limited. 2, Literature analysis results for drug laws223references were Searched, these documents involving138Chinese traditional medicine,the frequency of the top10is huangqi (9%), danshen (6.4%), cornel (4.8%), yam (4.7%), born dihuang (4.3%), chuanxiong (3.5%), poria cocos (3.4%), angelica (2.9%), motherwort (2.9%)and rhubarb (2.3%). By drug class frequency statistics, increase qi medicine to the fore (20.7%), promoting blood circulation medicine (19.9%), nourish "Yin" medicine (9.6%), astringent medicine (8.6%), heat medicine (8.3%) are also take the larger proportion. Drug clustering analysis showed that, commen drug couple are in the following:(1) drugs to profit of qi and activate blood circulation, such as huangqi and danshen.(2) drugs to Promoting blood circulation, such asrhubarb, leeches.(3) drugs to activate blood circulation and eliminate stasis class,such as chuanxiong, angelica, safflower, walnut,earthworm, which are the parts of Taohong Siwu soup;(4) drugs to increase the kidney Yin, such as dogwood, yam, tuckahoe, ripe dihuang, zexie, peony skin, all of these6drugs formed Liuwei Dihuang pill.3, Expert questionnaire survey resultsAll the experts who Participate in the questionnaire survey think the clinical symptom is complex, the top10are lack of power (95.7%), waist acid (78.3%), bubble urine (56.5%), nocturia (52.2%), thirsty (47.8%), see things fuzzy (43.5%), dizzy(39.1%), defecate rare (39.1%), shortness of breath (34.8%), ringing in the ears (30.4%), and dropsy (34.8); disease properties in the top3are Qi deficiency (100%), qi and blood stasis (91.3%), Yin deficiency (78.3%); the type of syndrome is complex, the top3are Qi and Yin deficiency (16.2%), Qi and Yin deficiency and blood stasis (8.8%), Qi deficiency in spleen and kidney (18.8%)22experts in23have a think of combining traditional Chinese and western medicine treatment is the best effect for the third phase of diabetic nephropathy,1experts think TCM is the best.In the choice of clinical prescriptions to the third phase of diabetic nephropathy, Liuwei Dihuang pill caughts the highest frequency (30.6%).4, META-analysis resultsA total of92articles were choosen, by rejecting the articles which does not conform to the criteria,10pieces about Liuwei Dihuang pill/soup,2about Guifu dihuang pill or Jinkui shenqi pill were left, because the latter literature number is too less to analysis, so only take META analysis to the articles about Liuwei Dihuang pill/soup. The literature retrieved in this study were1to3points. In three of retrieved literature, statistical analysis of UAER decreased value of the group about Liuwei Dihuang Pill/decoction and basic treatment were dealt, In five of that, statistical analysis of UAER decreased value between the group were dealt about Liuwei Dihuang Pill/decoction combined ACEI/ARB class with ACEI/ARB, In two of that, statistical analysis of UAER decreased value between groups about Liuwei Dihuang Pill/decoction with ACEI/ARB class. Test overall effect show that drop of UAER of Liuwei Dihuang Pill/Decoction group treat the third phase of diabetic nephropathy is more than control group (P<0.00001,95%CI are25.71～28.88,52.61～64.62, and13.11-29.35). The effects of therapy for the third phase of diabetic nephropathy using Liuwei dihuang pill/soup were positive,which provided theoretical evidences for clinical medication. The asymmetry presented in the funnel plot might be related to the publication bias and design of clinical trails.5, Clinical randomized trials results60patients with the third phase of diabetic nephropathy join in to the test, with microalbuminuria excretion rate36.0to297.4mg/24h, average (131.41±71.96mg/24h).50of these patients with Yin deficiency type and10of Yang deficiency, were divided into experimental group (31cases),and control group (29cases). After12weeks treatment, The extent of the decline of UAER in experimental group, the main evaluation index with a significant difference (f=4.997, P=0.029) compared with the control group. The extent of the decline of TPU, A/C, FBG, HbAlc、TC and TG are the second evaluation index, there are no statistical differences between the two greoups (P>0.05).After4weeks treatment, the extent of the decline of TCM syndrome scoring in experimental group, which is also a second evaluation index,has a a significant difference (f=9.826, P=0.003) compared with the control group, and this difference remain till the end of the test (f=8.533, P=0.005After8weeks treatment,f=14.75,P=0.000After12weeks treatment. To the detail, the extent of the decline of TCM syndrome scoring in Lumbar debility (f=6.693, P=0.012), abdominal distension (f=16.791, P=0.000), head heavy (f=8.073, P=0.006), low back pain (f=6.741, P=0.012), edema (f=5.240, P=0.0026) appear the statistical differences between the two greoups.ConclusionThis research find out a better solution through the large sample analysis of literature, META-analysis and expert questionnaire survey, and test its efficacy and safety to the the third phase of diabetic nephropathy through the standard clinical trials. It is shown that confirmed compared with western medicine therapy, optimization scheme characted by ACEI/ARB joint LiuWei/Guifu dihuang pill can more effectively reduce UAER in patients of the third phase of diabetic nephropathy, improving their clinical symptoms and their quality of life, and at the same time adverse reactions and1damage in aboratory index was not found. The scheme can be promoted and for the purpose of further regulating and guidance of traditional Chinese and western medicine treatment of the third phase of diabetic nephropathy.