A Study About Urinary Metabolomics Of Contrast-induced Nephropathy Associated With Percutaneous Coronary Intervention

Objective:To use liquid chromatography-mass spectrometry(LC-MS)to detect and compare the urine of patients who developed contrast-induced nephropathy(CIN)after percutaneous coronary intervention(PCI)and those with normal kidney function.Multivariate statistical methods were used to analyze the data and identify metabolic differences between the CIN and control groups.The study aims to identify potential biomarkers for diagnosis of CIN and investigate the mechanisms of it’s pathogenesis.Methods:1.This study collected urine samples from 20 post-PCI patients(10 CIN and 10control)and processed them by high-speed centrifugation and filtration through a microporous membrane.The supernatant was then analyzed using LC-MS to obtain their metabolic profiles and related data.2.The collected high-resolution liquid chromatography-mass spectrometry(LC-MS)data was preprocessed using software such as Analysis Base File Converter and MS-DIAL for peak alignment,identification,and extraction.The normalized data matrix was then imported into SIMCA-P(Version 13.0,Umetrics,Sweden)software for supervised orthogonal partial least squares discriminant analysis(OPLS-DA)and t-test screening of significant changes in metabolites.Significant metabolites were selected based on VIP>2 and p<0.05 criteria using peak intensity calculation.3.Possible matching metabolites were searched against databases such as HMDB(www.hmdb.ca).Relevant literature was queried to confirm the information about the metabolites,and the most relevant differential metabolites were identified.Differential metabolites were subjected to statistical analysis and pathway enrichment analysis using the Bioincloud website(https://www.bioincloud.tech)and Metabo Analyst website(https://www.metaboanalyst.ca/).The results were then verified by querying relevant literature.Results:1.After processing urine samples from the CIN group and the control group using LC-MS technology,SIMCA achieved intuitive visualization of PCA,OPLS-DA,and other model score plots,and after verification by statistical methods,differences in metabolites between urine samples of CIN patients and control group patients were identified.2.Using the HMDB database to search for differential metabolites,a total of 16 differential metabolites,including N-Palmitoyl Arginine,Oxoglutaric acid,FAPy-adenine,and L-Glutamine were screened as potential biomarkers to assist in the early diagnosis of CIN.3.Pathway analysis of the 16 differential metabolites shown in the figure was performed using Pathway Analysis on the Metabo Analyst5.0 website.A total of 11 metabolic pathways were matched.According to the impact factor value and relevant literature,we believe that the biosynthesis pathway of arginine and the metabolic pathways of alanine,aspartate,and glutamate are most relevant to CIN.Conclusions:1.This study applied LC-MS technology to analyze urine samples from CIN patients and coronary heart disease patients who underwent PCI treatment but did not develop contrast-induced nephropathy(control group).Sixteen differential metabolites were screened out,which may serve as potential biomarkers to aid in the diagnosis of CIN.2.There are 11 metabolic pathways involved in the occurrence and development of CIN.According to experimental results,the biosynthesis pathway of arginine and the metabolic pathways of alanine,aspartate,and glutamate may play the most critical role in the occurrence and development of CIN.3.The biosynthesis pathway of arginine and the metabolic pathways of alanine,aspartate,and glutamate may play important roles in the occurrence and development of CIN.However,it is not clear whether these two metabolic pathways individually affect the occurrence and development of CIN or whether they work together.Further exploration and research are needed.