Metabonomic Research For Risk Facotors Of Progression For Chronic Kidney Disese With Stage 4

ObjectiveBy use of Chinese medicine“No disease prevention first,Prevent disease from changing”and the concept of preventive medicine.Metabolic study of risk factors of CKD4 progression was carried out to explore the biomark,metabonomic parthway and relationship between risk factors of CKD4 progression and the declined renal function;at the same time,to analysis change of CKD4 syndrome and study on syndrome metabolomics for relationship between base of syndrome and disease.Methods1.Metabolomic research of CKD4:cases were from patients with CKD4 and p rimary disease non-diabetic nephropathy in a multi-center treatment of fr om January 2013 to June 2015.Healthy control group was from Fangcun Dist rict of Guangzhou Li Jiao Community Survey in 2013.According to the stud y purpose,inclusion of qualified CKD4 cases for the three-month observat ion,eGFR<10%was as a stable group,eGFR>25%was as a progressive grou p,the use of a retrospective nested case-control study of CKD was to scr een stable group and progress group.By sex and age ± 5 years,a stable group and a control group matched,both age and eGFR were not statistica lly significant,comparable.Collected blood samples,after separation of the serum stored at the ultra-low temperature-80?.By using ultra perf ormance liquid chromatography-mass spectrometry technology for metabolo mics analysis,compound has significant difference(P<0.05)of among scr eened group.By searching HMDB(http://www.hmdb.ca/)database and KEGG(ht tp://www.genome.jp/kegg/)database identified potential biomarkers and me tabolic pathways.2.Syndrome research:analysis of CKD4 Progress group and stable group before and after the change,to explore the relationship between syndrome changes and CKD4 progression.Former CKD4 of stable and progressive stage on metabolic syndrome were studied,to explore objective material basis of different syndromes at a certain stage of the disease,providing the proof for the syndrome study.Result1.Metabonomic research:Comparison of CKD4 Stable of specific products before(group D)and after stable(group C),specific products were 15(P<0.05):Creatinine,N-Acryloylglycine,N1-Methyl-2-pyridone-5-carboxamide,2-Aminomuconic acid,Phosphohydroxypyruvic acid,Methylhippuric acid,Palmitic amide,0-Phosphotyrosin,Methylimidazole acetaldehydeN-Undecanoylglycine,Fumaric acid,Betaine,Oleamide,Oleic acid,Ceramides N-acylsphingosine?In the KEGG database found CKD4 of group C and group D energy metabolic pathways,there are differences in lipid metabolism pathway and amino acid metabolism pathways CKD4 Progress of CKD4 Progress of group B compared with group A,found specific metabolites 16(P<0.01):Creatinine,Fumaric acid,N-Acryloylglycine,2-Aminomuconic acid,3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid,7 a-Hydroxy-3-oxo-5b-cholanoic acid,LysoPE(20:4/0:0),Carnosine,Palmitic amide,Oleamide,Oleic acid,12-Ketodeoxycholic acid,Linoelaidyl carnitine,Ceramides,PS(16:0/14:0)),(PS(16:0/16:0)).CKD4 of specific metabolites relatively stable period,found that eig ht of the same metabolite:3-Carboxy-4-methyl-5-propyl-2-furanpropionic a cid,7 ?-Hydroxy-3-oxo-5?-cholanoic acid),LysoPE(20:4/0:0))Carnosine,12-Ketodeoxycholic acid),Linoelaidyl carnitine),PS(16:0/14:0)),PS(16:0/16:0))?Identified,of which a specific amino acid metabolites are lo cated on metabolic pathways exist in an amino acid metabolic pathways and lipid metabolic pathways,another six unidentified metabolic pathways.2.Syndrome research:30 cases of stable patients,6 people with syndromes were changes.6 female patients:four of them were from stable before“deficiency of sple en and kidney,turbid stasis obstructing collaterals" Changed to“defici ency of spleen and kidney,turbid stasis obstructing collaterals with dam p-heat syndromet",and two others were from deficiency of spleen and kidne y,turbid stasis obstructing collaterals with damp-heat syndrome changed to "deficiency of spleen and kidney,turbid stasis obstructing collateral s".Advances group of 30 patients,four with syndrome changed.1 female p atient:"deficiency of spleen and kidney,turbid stasis obstructing colla terals " Changed to“deficiency of spleen and kidney,turbid stasis obstr ucting collaterals with damp-heat syndrome".Male patients 3:1 "deficie ncy of spleen and kidney,turbid stasis obstructing collaterals" Changed to "deficiency of spleen and kidney,turbid stasis obstructing collatera ls with damp-heat syndrome".2 "deficiency of spleen and kidney,turbid s tasis obstructing collaterals with damp-heat syndrome" Changed to deficie ncy of spleen and kidney,turbid stasis obstructing collateralsConclusionThrough the study,eight biomarkers of CKD4 advanced group and their metabolic pathways were related to the disorders of amino acid metabolic pathway and lipid metabolic pathways.According to the Logistic regression model,LysoPE(20:4/0:0),12-Ketodeoxycholic acid,Linoelaidyl carnitine,three biomarkers were associated with declined eGFR.Disease may play a certain effect on the syndrome,because,if the diseases were common with syndrome,the metabolites were different.