Altered Serum Bile Acid Profile Associated with Chronic Allograft Dysfunction in Kidney Transplant Recipients.
Altered Serum Bile Acid Profile Associated with Chronic Allograft Dysfunction in Kidney Transplant Recipients.
复制标题
肾移植受者血清胆汁酸谱的改变与慢性同种异体移植功能障碍相关
DOI：
10.12659/aot.937974
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发表时间：
2022-11-18
影响因子：
1.1
通讯作者：
Bai Y
中科院分区：
文献类型：
--
作者：
Li Y;Zhang H;Dai X;An Y;Li Y;Yan L;Shi Y;Fan J;Gong X;Zhang L;Zou Y;Wang L;Bai Y
慢性同种异体移植物功能障碍（CAD）是肾移植受者（KTR）移植物失功的主要原因。胆汁酸（BA）在调节炎症过程中发挥重要作用，而炎症过程是导致CAD发生的主要因素。本研究的目的是评估KTR中BA代谢失调与CAD之间的关联。材料/方法采用UPLC-MS/MS法测定43例健康对照（HC）和131例KTR患者血清中15种BA的含量，并根据eGFR水平将KTR分为肾功能稳定（STA）组和CAD 1、CAD 2组。通过RT-PCR测定循环CYP 7A 1、CYP 7 B1、CYP 27 A1和SLCO 2B 1 mRNA水平。结果4组间总BA浓度相当。然而，与HC相比，KTR显示出显著不同的BA谱。与其他3组相比，患有严重CAD的KTR（CAD 2）的非结合BA和继发性BA（SBA）显著降低。KTR的SBAs/原发性BA（PBAs）比值显著低于HC，这在3个KTR组中相当。结合/非结合BAs比值随着移植物功能的恶化而显著增加，相关性分析进一步证实了这一点。差异相关网络分析显示，在CAD进展过程中存在类内和类间BA协同调节的扰动。CYP 7 B1和CYP 27 A1基因相对表达量与eGFR呈正相关。结论：在CAD的KTR中，BA种类谱而非总BA浓度显著改变。从非共轭BA向共轭BA，SBAs向PBAs的转变，以及不同的成对BA共调节模式是CAD KTR的主要特征。
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/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.