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":"肾移植受者血清胆汁酸谱改变与慢性同种异体移植物功能障碍相关。","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":"27 ","pages":"e937974"},"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":"{\"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\":\"27 \",\"pages\":\"e937974\"},\"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}","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
摘要
慢性同种异体移植物功能障碍(CAD)是肾移植受者(KTRs)中移植物损失的主要原因。胆汁酸(BAs)在调节炎症过程中发挥重要作用,是CAD发展的主要因素。本研究的目的是评估KTRs中BAs代谢失调与CAD之间的关系。材料与方法采用UPLC-MS/MS对43例健康对照者和131例ktr患者血清中15种BA进行了测定。根据eGFR水平将ktr分为稳定肾功能组(STA)和CAD1、CAD2组。RT-PCR检测循环CYP7A1、CYP7B1、CYP27A1和SLCO2B1 mRNA水平。结果4组间总BA浓度具有可比性。然而,与hcc相比,KTRs显示出明显不同的BAs谱。与其他3组相比,严重CAD (CAD2)的KTRs的非共轭BAs和继发性BAs (SBAs)显著降低。KTR组的SBAs/primary BAs (PBAs)比率明显低于hc组,这在3个KTR组中是相当的。随着同种异体移植物功能的恶化,共轭/非共轭BAs比值显著增加,相关分析进一步证实了这一点。差异相关网络分析显示,在CAD进展过程中,类内和类间BA协同调节存在扰动。此外,CYP7B1和CYP27A1的相关基因表达量与eGFR呈正相关。结论:在患有CAD的KTRs中,BA的种类谱,而不是总BA浓度显著改变。非共轭BAs向共轭BAs转变,SBAs向PBAs转变,以及明显的成对BAs协同调节模式是CAD KTRs的主要特征。
Altered Serum Bile Acid Profile Associated with Chronic Allograft Dysfunction in Kidney Transplant Recipients.
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.