| Objective:Finding the arginine metabolites in chronic kidney disease(CKD)1-4 stages patients with metabolomics analysis methods and exploring their diagnostic value and the relationship with cardiovascular diseases,so as to provide theoretical basis for early diagnosis and intervention in CKD.Methods:The 47 CKD patients admitted to the nephrology ward in the hospital from March 2018 to June 2018 were divided into CKD stage 1 group(13 cases),CKD stage 2 group(11 cases),CKD stage 3 group(11 cases)and CKD stage 4 group(12-cases)according to eGFR.Thirty healthy volunteers during the same period were selected.General data and laboratory results as well as carotid artery ultrasound and echocardiography indexes were collected from CKD patients and control group.Establishing the liquid chromatography-mass spectrometry(LC-MS)platform to obtain relevant data matrix information,then principal analysis(PCA)and orthogonal partial least squares-discriminant analysis(OPLS-DA)were applied to determine the metabolite profile with EZinfo software.According to the variable importance value and ANOVA to identify differential metabolites,matching HMDB database to obtain the metabolic biomarkers accurate information.ROC curves of metabolic biomarkers were drawn to evaluate their diagnostic values.Correlation analysis was conducted between the metabolic biomarkers and CKD related clinical complications,and a single factor analysis was performed on the metabolic biomarkers with laboratory results.Significant positive results were included into the regression equation for further multivariate regression analysis.Results:1.The average serum creatinine value was 59.80 μmol/L.The average serum creatinine value was 110.90 μmol/L.There was increasing tendency of creatinine,urea and proportion of hypertension,lipid-lowering drugs,prostaglandin E1 andα-ketoacids in CKD1-4 groups,but there was no significant difference in blood glucose and lipid indicators(P>0.05).2.PCA and OPLS-DA model analysis showed that the plasma metabolite profiles of control group and CKD-4 groups were significantly different.Compared with the control group,the plasma content of arginine,ornithine,citrulline,and ADMA were increased(P<0.05),and the increase of ornithine in CKD2-4 stage,citrulline in CKD1-3 stage,and ADMA in CKD1-2 and CKD3-4 stages had statistical significance.(P<0.05).3.The ROC curve of ADMA,citrulline and ornithine were drawn to identify eGFR<60 ml/(min·1.73m2),and the results showed that the area under the ADMA curve was 0.919 with the confidence interval of 0.865～0.981,the area under the ornithine curve was 0.914 with the confidence interval of 0.850～0.978,and the area under the citrulline curve was 0.911 with the confidence interval of 0.833～0.990.4.The correlation between the plasma asymmetric dimethylarginine level and clinical complications in 47 CKD patients was analyzed.It was found that the elevated ADMA level was associated with hypertension,left ventricular hypertrophy and carotid atherosclerotic plaque.5.Single factor analysis found that in CKD1-2 stages,plasma asymmetric dimethylarginine is related to eGFR,creatinine,pro-albumin,RDW,and NLR.The linear regression model found that creatinine is independently associated with ADMA.6.Single factor analysis found that in CKD3-4 stages,plasma asymmetric dimethylarginine is related to eGFR and urea.Conclusion:1.With the progression in CKD,arginine metabolites citrulline,ornithine and ADMA increased significantly,which can be used as potential biomarkers to predict the progression of CKD.2.ADMA in CKD patients is correlated with clinical cardiovascular diseases.Creatinine is independently associated with ADMA in the early stage of CKD,and the increase of ADMA in the late stage of CKD is related to eGFR and urea. |
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