Yamei Li, Hua Zhang, Xinhua Dai, Yunfei An, Yi Li, Lin Yan, Yunying Shi, Jiwen Fan, Xingxin Gong, Lei Zhang, Yuangao Zou, Lanlan Wang, Yangjuan Bai
{"title":"Altered Serum Bile Acid Profile Associated with Chronic Allograft Dysfunction in Kidney Transplant Recipients.","authors":"Yamei Li, Hua Zhang, Xinhua Dai, Yunfei An, Yi Li, Lin Yan, Yunying Shi, Jiwen Fan, Xingxin Gong, Lei Zhang, Yuangao Zou, Lanlan Wang, Yangjuan Bai","doi":"10.12659/AOT.937974","DOIUrl":null,"url":null,"abstract":"<p><p>BACKGROUND Chronic allograft dysfunction (CAD) is the leading cause of graft loss among kidney transplant recipients (KTRs). Bile acids (BAs) play an important role in regulating inflammatory process, which is the major contributor to the development of CAD. The aim of this study was to evaluate the association between BAs metabolic dysregulation and CAD in KTRs. MATERIAL AND METHODS Fifteen serum BA species were determined in 43 healthy controls (HCs) and 131 KTRs by UPLC-MS/MS. KTRs were grouped into stable renal function (STA) and CAD1 and CAD2 groups based on eGFR levels. Circulating CYP7A1, CYP7B1, CYP27A1, and SLCO2B1 mRNA levels were determined by RT-PCR. RESULTS Total BA concentrations were comparable among the 4 groups. However, KTRs showed significantly different BAs profiling compared to HCs. KTRs with severe CAD (CAD2) had significantly lower unconjugated BAs and secondary BAs (SBAs) compared to the other 3 groups. KTRs had significantly lower SBAs/primary BAs (PBAs) ratios than HCs, which were comparable among the 3 KTR groups. Conjugated/unconjugated BAs ratios increased significantly with the deterioration of allograft function, which was further confirmed by correlation analysis. Differential correlation network analysis revealed that perturbations in intraclass and interclass BA coregulation existed during CAD progression. Moreover, relative gene expressions of CYP7B1 and CYP27A1 were positively correlated with eGFR. CONCLUSIONS BA species profiling, but not total BA concentrations, was significantly altered in KTRs with CAD. The shifts from unconjugated BAs toward conjugated BAs, SBAs toward PBAs, and distinct pairwise BAs coregulation patterns were the main characteristics of KTRs with CAD.</p>","PeriodicalId":7935,"journal":{"name":"Annals of Transplantation","volume":null,"pages":null},"PeriodicalIF":1.1000,"publicationDate":"2022-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c5/a6/anntransplant-27-e937974.PMC9680208.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Transplantation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.12659/AOT.937974","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"SURGERY","Score":null,"Total":0}
引用次数: 0
Abstract
BACKGROUND Chronic allograft dysfunction (CAD) is the leading cause of graft loss among kidney transplant recipients (KTRs). Bile acids (BAs) play an important role in regulating inflammatory process, which is the major contributor to the development of CAD. The aim of this study was to evaluate the association between BAs metabolic dysregulation and CAD in KTRs. MATERIAL AND METHODS Fifteen serum BA species were determined in 43 healthy controls (HCs) and 131 KTRs by UPLC-MS/MS. KTRs were grouped into stable renal function (STA) and CAD1 and CAD2 groups based on eGFR levels. Circulating CYP7A1, CYP7B1, CYP27A1, and SLCO2B1 mRNA levels were determined by RT-PCR. RESULTS Total BA concentrations were comparable among the 4 groups. However, KTRs showed significantly different BAs profiling compared to HCs. KTRs with severe CAD (CAD2) had significantly lower unconjugated BAs and secondary BAs (SBAs) compared to the other 3 groups. KTRs had significantly lower SBAs/primary BAs (PBAs) ratios than HCs, which were comparable among the 3 KTR groups. Conjugated/unconjugated BAs ratios increased significantly with the deterioration of allograft function, which was further confirmed by correlation analysis. Differential correlation network analysis revealed that perturbations in intraclass and interclass BA coregulation existed during CAD progression. Moreover, relative gene expressions of CYP7B1 and CYP27A1 were positively correlated with eGFR. CONCLUSIONS BA species profiling, but not total BA concentrations, was significantly altered in KTRs with CAD. The shifts from unconjugated BAs toward conjugated BAs, SBAs toward PBAs, and distinct pairwise BAs coregulation patterns were the main characteristics of KTRs with CAD.
期刊介绍:
Annals of Transplantation is one of the fast-developing journals open to all scientists and fields of transplant medicine and related research. The journal is published quarterly and provides extensive coverage of the most important advances in transplantation.
Using an electronic on-line submission and peer review tracking system, Annals of Transplantation is committed to rapid review and publication. The average time to first decision is around 3-4 weeks. Time to publication of accepted manuscripts continues to be shortened, with the Editorial team committed to a goal of 3 months from acceptance to publication.
Expert reseachers and clinicians from around the world contribute original Articles, Review Papers, Case Reports and Special Reports in every pertinent specialty, providing a lot of arguments for discussion of exciting developments and controversies in the field.