The Clinical Research Of Improving Achievement Level And Tubular Damage Of Diabetic Nephropathy With Staging Differentiation And Treatment Of TCM

BackgroundDiabetic nephropathy(DN) is one of the most common and serious chronic microvascular complications of Diabetes Mellitus (DM). DN has gradually become the first cause of end-stage renal disease (ESRD), which is bound to bring a heavy personal, family, social economic burden, meanwhile the quality of life is in serious declining. The modern medical treatment of DN includes taking a more reasonable diet, hypoglycemic, antihypertensive, lipid-lowering, the application of ACEI, ARB, etc., although there is certain effect, but it is hardly to prevent the development and progression of the disease effectively. Therefore, how to prevent and treat DN effectively is the problem to solve in medical field. Chinese medicine has made some progress in the treatment of early DN by blocking the progress of the disease and protecting renal function, and showed its unique advantages. At present, the concept of people about DN control have changed from treatment to prevention.DN belongs to the category of chronic diseases, chronic disease management can meet the diverse needs of patients with chronic disease prevention and control process, and help enhance health awareness and healthy concept. In essence the preventive treatment of disease thinking in Chinese medicine has the same objective with the current advocated management of chronic health. Diabetic nephropathy belongs to Chinese "Diabetes kidney disease" category, the basic pathogenesis is the deficiency in the "root" and excess in the "branch". With the progression of the disease, the deficiency of Qiyin will transfer to Yang deficiency of the spleen and kidney. The symptoms are different in different stages and individual, but blood stasis throughout the DN course of the disease is always important syndrome. Diagnosis and treatment is the essence of TCM. Based on the characteristics of DN pathogenesis,TCM staging diagnosis and treatment is a must. At present it is lack of systematic research on the essence of the disease TCM climate objective basis and TCM symptom element, as well as organic combination of TCM diagnosis and treatment and chronic disease management. With the deepening of the DN research, it is recognized that the development and prognosis of DN is not only associated with glomerular damage, but also depends on the presence and degree of severity of the renal tubulointerstitial lesion. Urinary retinol binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG) are related with the extent of early renal tubulointerstitial damage. The thesis is one part of the research based on the Beijing Municipal Administration of Traditional Chinese Medicine Chinese medicine characteristics and advantages of the disease prevention and major diseases in medicine science and technology research topics, that is a multi-center clinical study on the long-term efficacy of TCM installments Treating diabetic nephropathy under chronic disease management model(project number JJ2011-73). It is also a part of the research supported by Beijing Municipal Science and Technology Commission, the capital of the clinical characteristics of applied research, named "installment Diagnosis and Treatment of traditional Chinese medicine combined with chronic disease management to improve the long-term efficacy of diabetic nephropathy clinical research" part of the (project number Z121107001012012). In order to provide the basis for the establishment of prevention and treatment programs of DN chronic disease management with Chinese characteristics, the research evaluates the effect of Chinese herbal to prevent and treat DN from the primary efficacy endpoint compliance level, renal tubular damage markers and so on.Objective1.Combine TCM staging diagnosis and Treatment with chronic disease management model in DN, evaluate the efficacy of staging diagnosis and Treatment by multi-center, prospective, open-label study from the aspects such as the primary efficacy endpoint. Controlled level of compliance, renal tubular damage markers, et al. Observe the role of staging diagnosis and Treatment on improving efficacy and renal damage, delaying the progression of DN, to better reflect the prevention and treatment of health policy and the advantages of Chinese medicine.2.Look for sensitive markers for the early diagnosis of DN by comparing study tubular damage indicators URBP and UNAG between diabetes patients and DN ones.3.Make a correlation analysis between TCM symptoms of DN and renal tubular damage indicators to provide an objective basis for DN staging diagnosis and treatment.MethodsPart one1. Object:patients with DN Ⅲ, Ⅳ stages from Wangjing Hospital, Hospital of Pinggu, Daxing District Hospital, Jiangtai community service centers, the Fatou Community Service in-patient or out-patient. September2012to December2012. 2.Interventions:A prospective study of central randomization method. Subjects are divided into two groups,60patients for the treatment group, to accept staging diagnosis and treatment, chronic disease management, conventional Western medicine treatment as well, the other60patients as the control group, treated with conventional Western.3. Observation indexes:Albuminuria, renal function, glycosylated hemoglobin, lipids, tubular damage indicators URBP and UNAG, the efficacy of clinical symptoms, endpoint events.Part two1. Object:patients from China Academy of Traditional Chinese Medicine, Wangjing Hospital, hospitalized patients with type2diabetes and type2diabetic nephropathy III and stage IV patients of the30cases, medical centers30cases of healthy people, October2012to March2013.2. Methods:by immune transmission turbidimetric method URBP; the4HP-NAG substrate method for determination of UNAG.3. Observation indexes:URBP, UNAG.Part three1. Object:patients with DN Ⅲ, Ⅳ stages from Wangjing Hospital, Hospital of Pinggu, in-patient or out-patient, September2012to December2012.2. Methods:record TCM symptoms scores, by immune transmission turbidimetric method URBP; the4HP-NAG substrate method for determination of UNAG. make person correlation analysis between TCM syndromes and URBP, UNAG3. Observation indexes:TCM syndromes,URBP, UNAG Correlativity.ResultsPart one120cases were enrolled in the study, including60cases in treatment group and60cases in control group. Baseline data were compared with the comparable.1. In treatment group markedly effective rate of proteinuria decreasing was33.3%, efficiency was31.7%and Total efficiency was65.0%. In control group, markedly effective rate of proteinuria decreasing was13.3%, efficiency was21.7%and Total efficiency was35.0%. Total efficiency by X2test, P<0.05, the difference was statistically significant.2. In treatment group markedly effective rate of renal function was26.7%, efficiency was40.0%and Total efficiency was66.7%. In control group, markedly effective rate of renal function was8.3%, efficiency was15.0%and Total efficiency was23.3%. Total efficiency by X2test, P<0.05, the difference was statistically significant.3.The compliance rate of glycosylated hemoglobin of treatment group was78.3%, while31.7%of control group. The compliance rate by X2test, P<0.01, the difference was statistically significant between two groups. The compliance rate of HDL、LDL、TG of treatment group was separately75.0%,78.3%,75.0%,while28.3%,31.6%,33.3%of control group. The compliance rate by X2test, P<0.01, the difference was statistically significant between two groups.4. In treatment group markedly effective rate of clinical main symptoms was45.0%, efficiency was35.0%and Total efficiency was80.0%. In control group, markedly effective rate of clinical main symptoms was11.7%, efficiency was18.3%and Total efficiency was30.0%. Total efficiency by X2test, P<0.01, the difference was statistically significant.5. After treatment URBP of treatment group decreased significantly compared with that of control group, P<0.05, the difference was statistically significant between the two groups. There was a statistically significance about URBP of treatment group between before treatment and after treatment P<0.05. There was a statistically significance about UNAG of treatment group between before treatment and after treatment P<0.05. compared with control group, after treatment UNAG had downward trend, but no significant difference P>0.05between two groups.6. The early DN proteinuria endpoint event rate was3.1%in treatment group and6.4%in control group. Clinical stage DN proteinuria endpoint event rate was7.1%and the control group was13.8%. the overall incidence rate of proteinuria endpoint event rate was5.0%in treatment group,10.0%in control group. The total incidence of periods DN renal function endpoint event was6.7%in treatment group,15.0%in control group. From above data between the two groups, there was no statistically significant difference P>0.05. There were no deaths in two groups.Part two1. There was statistically significant difference of URBP among normal control group, DM group and DN group (P<0.01). URBP of DM group had statistically significant difference compared with that of DN group (P<0.05). 2. There was statistically significant difference of UNAG among normal control group, DM group and DN group (P<0.05,P<0.01). UNAG of DM group had statistically significant difference compared with that of DN group(P<0.05).Part three1. Diabetic nephropathy in patients with stage Ⅲ TCM syndromes:the occurrence probability of the top ten Chinese medicine syndrome are as follows: soreness and weakness in lower back, the foreign body sensation of eyes, dry mouth, lumbago, tired or fatigue, thirst, numbness, forgetfulness, urinary frequency, lower extremity edema. Diabetic nephropathy stage IV probability of occurrence of the top ten Chinese medicine syndrome:lumbago like warm, soreness and weakness in lower back, numbness in the hands and feet, lower extremity edema, fatigue, forgetfulness, hand-foot no warm, itchy skin, the foreign body sensation of eyes, intolerance of cold.2.There was statistically significant difference of URBP and UNAG respectively between Diabetic nephropathy with stage Ⅲ and stage Ⅳ.(P<0.05).3. TCM syndrome urinary frequency with diabetic nephropathy stage Ⅲ was positive related respectively to URBP and UNAG.(r=0.869, P<0.01)(r=0.726, P <0.01); TCM syndrome lower extremity edema with diabetic nephropathy stage Ⅳ was positive related respectively to URBP and UNAG.(r=0.857, P<0.01),(r=0.821, P<0.01).Conclusions1.It is a new model to integrate TCM staging diagnosis and treatment and chronic disease management. TCM staging diagnosis and treatment can improve clinical symptoms, decrease proteinuria, protect renal function, improve the level of compliance about blood glucose and lipid, and improve the indicators of renal tubular damage as well. Chinese medicine chronic disease management reflects the diagnosis and treatment of traditional Chinese medicine and holistic principles, giving full play to the prevention and treatment of diabetic nephropathy of Traditional Chinese Medicine and the advantages of delaying the progress of the disease.2. URBP and UNAG has been increased when the urine protein is negative in patients with type2diabetes. That suggests these two tubular damage indicators can be used as sensitive makers of early diagnosis of DN.3. Qiyinliangxu is the common TCM syndrome type in diabetic nephropathy stage Ⅲ, and Pishenyangxu is the common type in stage IV with blood stasis throughout the course of disease. TCM syndrome urinary frequency with diabetic nephropathy stage Ⅲ was positive related respectively to URBP and UNAG. TCM syndrome lower extremity edema with diabetic nephropathy stage IV was positive related respectively to URBP and UNAG. The connection point between TCM syndromes and renal tubular damage related indicator is the "water" pathological elements.Innovations1. Chinese medicine chronic disease management model is an innovation:In this study, TCM staging diagnosis and treatment integrates with chronic disease management mode, which is in line with the new contemporary medical concept of combining prevention with control, Promoting health and slowing progress of the chronic disease.2. Innovative research and design ideas:to use a multi-center, large sample, randomized controlled clinical prospective study is innovative idea.3. Innovative research:to research the efficiency of TCM staging diagnosis and treatment from improving the level of compliance and renal tubular damage indicators. to compare tubular damage indicators URBP and UNAG between diabetes patients and DN ones. To make a correlation analysis between TCM symptoms of DN and renal tubular damage indicators and find the "water" pathological elements is the connection point of them.