The Preliminary Research Of The Clinical Curative Effect About Qidan Dihuang Grain To The Third Phase Of Diabetic Nephropathy

ObjectiveDiabetic nephropathy (DN) is the most common complication of diabetes,is also one of the main cause of death in patients with diabetes.In 2010, China’s diabetes epidemiological surveys show that more than 20 years old crowd prevalence has been up to 9.7%, the number of diabetes has more than 9240 million,China has become one of the largest of the world’s diabetic population.Newly diagnosed type 2 diabetes, microalbuminuria occurrence rate is as high as 20.5%, if not active treatment, there will be 20-40% of the patients eventually develop into end-stage renal failure (ESRD),and about 53% of patients will die.At present,the treatment of DN mainly adopt the method of comprehensive treatment, such as guidance of diet, control blood pressure, blood sugar and lipid, etc. In addition, a large number of literatures show that lower urinary protein can delay the progression of diabetic nephropathy,so urinary protein therapy has become a therapeutic target for diabetic nephropathy.Angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in addition to the decompression, also can significantly reduce the urine protein,and delay the onset of end-stage renal failure (ESRD), but because there are expensive, side effects such as dry cough, and adverse factors such as liver and kidney toxicity, the clinical application is subject to certain constraints.So far the combine traditional Chinese and western medicine has many problems in the treatment of DN:1, Quite a number of solutions is simply relying on the doctor’s clinical experience of the individual, which subjectiveand optional the gender is strong, and not by making scientific 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.In order to solve the above problem, this research hope to infer a better solution through the large sample analysis of literature and expert questionnaire survey by using the method of evidence-based medicine, summarize the etiology and pathogenesis of diabetic nephropathy, main clinical manifestation, clinical syndrome, unilaterally, Chinese traditional medicine compound traditional Chinese medicine, proprietary Chinese medicine, etc.Finally we 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:Medline(1979-2009),VIP(1989-2009),Wanfang full-text database(1982-2009) and CMA digital periodicals(1994-2009),CBM disc (1990-2009)and reference lists of all papers identified also were checked. Literature between 1984-2009 were choosen,which relating to Syndrome type, diagnosis and treatment plan and Chinese and western drugs, etc.Then use Epidata3.1 to establish database of information acquisition, adopt the method of double entry to input data and correction,using SPSS13.0 software to make the statistical analysis.2, META-analysisComprehensive collection literatures through the Medline,VIP,Wanfang full-text database and CMA digital periodicals,CBM disc.The literatures of randomized controlled about the third phase of diabetic nephropathy using yiqi yangyin huoxue decoction combined withBenazepril were retrieved and systematically evaluated.The qualities of all literatures were assessed according to Cochrane kidney group adopts the evaluation standard. All data were analyzed using Revman5.0 software.Finally assessed efficacy and safety of it scheme.3, Expert questionnaire surveyExpert questionnaire on the basis of reference literature survey and solicit opinions from the experts, are mailed to diabetes kidney disease expert who from the 18 levels of first-class hospitals and 3 medical colleges and universities.Using Epidata3.1 data management, and double people entry independently the data, after verification, correction, then lock the database.The databasechange into SPSS format, sum up it common symptoms, syndrome type, commonly used prescription, etc.4, Clinical randomized trialsAccording to the literature investigation, expert questionnaire and META-analysis results, with a final determination to optimization scheme characted by qi blood- activation combined with ACEI/ARB to the third phase of diabetic nephropathy. We consulted advices form a number of famous Chinese medicine experts and professor Luo Ren, developed Qidan Dihuang grain,it including 30 gramsof astragali,15 grams of salvia miltiorrhiza,15 grams of rehmanniae,15 grams of yam and 5grams of liquorice.Using a randomized, open, parallel, 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 of 2300 articles were choosen,82 of them involved card type distribution, 223 of them involvede clinical treatment,117 of them involved different sorts of TCM treatment, and 563 of them involved patent chinese medicine and single chinese medicine.The results of this study show that disease resistance to qi+Yin+Blood of the triple combination of the highest frequency of occurrence, accounting for 71.3%, Stasis Syndrome Qiyinliangxu folder broad syndromes of diabetic nephropathy can be preliminary description of Qiyinliangxu folder stasis is the most basic of type 2 diabetic nephropathy syndrome type. In terms of medicine,it involving a total of 138 kinds of traditional Chinese medicine. The frequency of drug residing in the top 5, astragalus, red sage root, dogwood, yams, Rehmanniae.2, META-analysis resultsA total of 92 articles were choosen, only have 9 RCT literature, including 686 cases of type 2 diabetic nephropathy with early, Methodological quality assessment show the research quality is not high, only one class B, and the remaining eight are C.Meta analysis showed that:compared with those use of benazepril, the benazepril combined with qi blood-activation that was lower in early the diabetes nephrosis patient urinary albumin excretion rate [WMD=-23.49,95% CI (87.54-0.44,)], serum creatinine [WMD=-48.99,95% CI (90.59,7.40)], urea nitrogen [WMD=-1.91,95% CI (4.82,1.00)], glycated hemoglobin [WMD=-1.08,95% CI (1.64,0.54)], triglycerides [WMD=-1.49,95% CI (2.90,0.09) advantagesThe asymmetry presented in the funnel plot might be related to the publication bias and negative results were published.One group 2 cases reported in the literature to a dry cough, may be associated with use of ACEI drugs, the rest of the document does not appear significant adverse reactions and side effects.3,Expert questionnaire survey resultsA total of 23 experts participated in the questionnaire, The results show that disease resistance to qi+Yin+Blood of the triple combination of the highest frequency of occurrence, accounting for 100%, the next are blood stasis (91.3%) and Yin deficiency (78.3%); the type of syndrome is complex, the top 3 are Qi and Yin deficiency(16.2%),Qi and Yin deficiency and blood stasis (8.8%),spleen and kidney deficiency (8.8%). In the choice of clinical prescriptions to the third phase of diabetic nephropathy, Liuwei Dihuang pill caughts the highest frequency (30.6%).The result of literature investigation and expert questionnaires are basically same, it is qi+Yin +Blood of the triple combination.4, Clinical randomized trials resultsWe completed 60 cases,there are three cases were not completed, the depigmentation rate is 5%,one cases were excluded, eliminating rate is 1.67%. Various project indicatorsof two groups about the demographic characteristics, vital signs, condition data and so on are similar, there was no significant difference after statistics processing (p> 0.05). After 12 weeks of treatment, the various indexes of two groups of patients could improve, the difference was statistically significant (P< 0.05). After 12 weeks of treatment, compare with the control group, the use of Qidan Dihang grain group with lower 24 hour urinary albumin excretion rate (ALBU)and fasting blood glucose (FPG),the difference was statistically significant (P< 0.05).The extent of the decline of TPU, A/C, HbA1c、TC and TG are the second evaluation index, there are no statistical differences between the three greoups (P> 0.05). Pure western is not improved significantly the symptoms, using Qidan Dihuang grain can better alleviate the uncomfortable symptom of patients.In the process of test, we did not find the side effects of Qidan Dihang grain.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 Qidan Dihuang grain 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 and damage in aboratory index was not found. This scheme has opened up a new path for the treatment of the third phase of diabetic nephropathy.