Base On The Biomarkers Early Warning Evaluation Kidney Injury By TCM

BackgroundChinese medicine is the treasure of medicine in China, its good therap-eutic effect being recognized and affirmed all over the world. Under the guidance of TCM theory, the traditional Chinese medicine through "xiang xv", "xiang shi", "xiang wei" and "xiang sha" improve its effectiv-eness and reduce side effects. In China, it’s prevalent phenomenon that you see the doctor of traditional Chinese medicine and eat Chinese traditional medicine when you’re illness.A scholars in China reported Mutong cause of acute renal failure in 1964, but at that time did not caused widespread attention. Until 1993, Vanherweghem, a Belgian doctor disclosed some women in Belgian taking the herbal tea contains Radix Aristolochiae Fangchi caused end-stage renal failure.The news opened for a traditional Chinese medicine safety discus-sion.Reports of adverse reaction of Chinese medicine in clinical is on the rise over this years, especially the damage to the kidney, mainly for renal toxic reaction and allergic reaction. According to statistics, in patients with acute renal failure in recent years, about 25% are caused by drug renal damage, it is a serious threat to human health. In recent years, international medical technology level had enhance a lot, but the incidence of renal failure and mortality have no signs of decline. kidney function can be restored,If we In the early detection of abnormal changes in kidney function. In this study,we used novel biomarkers of kidney injury in the safety evaluation of traditional Chinese medicine (TCM), early detection of renal damage caused by drugs. In order to improve the safety of long-term use of Chinese medicine. ObjectivesWe propose a working hypothesis:AKI early biomarkers can timely and specific reflection of kidney damage caused by different reasons,through the detection of these markers can evaluate the use of drugs or treatment effects on renal function in clinical. In first, our study screened by animal experiments is suitable for clinical research of several biomarkers,cons-truction research system of renal disease, further analysis of clinical samples for testing, verify the feasibility of this method, provide the basis for further clinical research.MethodsResearch using animal models and clinical samples the way of combining, the concrete content as follow:1. Using Caulis Aristolochiae Manshuriensis To observe the renal changes of aristolochic acid-induced nephrotoxicity by using large dose of Caulis Aristolochiae Manshuriensis Extract (CAME) or aristolochic acid I in rats, and investigate at different time points to collect the blood and urine samples then observe the changes of AKI early biomarkers based methodology; By ELISA, alkaline picric acid, colorimetric detection method.2. Urine sample from Phase I clinical trial of "Muxiangweitai" was detec-tion. Combination of this project and experiment on animals to establish a methodology for the research and analysis early renal disease. By ELISA, alkaline picric acid, colorimetric detection method.3. Using the methodology established from animal experiment to evaluated renal function of hospitalized patients on long-term use of traditional Chinese medicine. The study will answer wether AKI kidney early biomarkers can be widely used in clinical studies.AS a experimental basis, for the evaluation of use drugs and treatment effect in clinical. Results1.1 The model of Acute kidney injury in rat was established, after treatment of Caulis Aristolochiae Manshuriensis or AAI monomer in threesecutive days.1.2 Observation from kidney injury factor and pathological, "Mutong" group renal damage degree is more serious than "AAI" group with the same content of AAI.1.3 To detect the contents of kidney injury factors in serum or urine, by ELISA or enzymatic, we found a time sequence of early kidney injury factor is:NGAL>CystatinC、TP、ALB>sCr、BUN.2.1 According to<Phase I clinical drug tolerance test plan of Mu xiang weitai, drug tolerance was provided with a single or multiple dosing to subjected crowds. All adverse events are characterized by abnormal labora-tory examination, systemic adverse events has not been found;2.2 There are four subjects in single-dose group to adverse events occur, a total of 6 times; Seven subjects in multiple dosing group appear harmful response, a total of 14 times.2.3 To detect the contents of kidney injury factors in serum or urine, by ELISA or enzymatic, Each dose group of the adverse events of case analysis, failing to prove that dose and dose effect relationship in the adverse events occur.3.1 sCr, BUN, ALBU, TP, NAG in the patients of kidney disease are respec-tively 3.8 times,3 times,3.8 times,26.8 times and 6.8 times than healthy people.3.2 When serum creatinine and urea did not see abnormalities of patients hospitalized in long-term use of traditional Chinese medicine, The ALBU, TP, NAG are respectively 1.35 times,1.81 times and 1.35 times. The study of 46 of long-term use of traditional Chinese medicine (TCM) in hospitalized patients, there are 19 people TP on rise, accounting for 41.3% of the total. The study of 46 of long-term use of traditional Chinese medicine (TCM) in hospitalized patients, there are 4 people ALB on rise, accounting for 8.7% of the total. All the above data suggest that in terms of reflecting the early renal damage, urine TP, NAG appear much more earlier than the serum creatinine and urea ConclusionStudy from animal experiments and clinical samples, we found urine TP、 ALB、NAG、NGAL、KIM-1 and CysC appear much more earlier than the serum creatinine and urea, in early kidney injury, and these factors are accurately reflect changes in renal function.