Wang Jing, Huang Siqi, Li Yuanchen, Fang Qiu, Wang Min, Zhu Huaijun
Department of Pharmacy, Nanjing Drum Tower Hospital the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.
Department of Pharmacy, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
PeerJ. 2024 Dec 18;12:e18729. doi: 10.7717/peerj.18729. eCollection 2024.
Microbiota-derived toxins indoxyl sulfate and hippuric acid were previously reported to be associated with altered pharmacokinetics of the immunosuppressant tacrolimus in liver transplant recipients, and ABC transporter proteins are likely to be involved in the transport of such substances, but the role has not been elucidated. The aim of this study was to assess the retention of indoxyl sulfate and hippuric acid in the plasma of liver transplantation subjects carrying different genotypes of and (changes in transporter activity due to genetic variation), and to explore whether genetic variation is involved in altering the relationship between microbe-derived toxins and tacrolimus pharmacokinetics.
Liver transplantation subjects treated with the immunosuppressive regimen tacrolimus, corticosteroids, and mycophyolate mofetil were included and divided into normal renal function group and chronic kidney disease group. The plasma concentrations of indoxyl sulfate and hippuric acid in two groups of liver transplantation subjects carrying different genotypes of and were compared. For genotype carriers with significant differences, the Pearson Correlation Coefficient method was further used to investigate the correlation between plasma indoxyl sulfate level and tacrolimus dose-corrected trough concentration in patients with different renal function status.
Carriers of the rs717620-24T variant exhibited high plasma indoxyl sulfate retention in patients with normal renal function, and furthermore, chronic kidney disease patients and patients with normal renal function exhibited indoxyl sulfate and tacrolimus in the normal function (β = -0.740, = 0.020) and reduced function groups (β = -0.526, = 0.005), respectively, showing a strong correlation with tacrolimus.
may be one of the pathways by which tacrolimus pharmacokinetics is altered by indoxyl sulfate.
先前有报道称，微生物群衍生的毒素硫酸吲哚酚和马尿酸与肝移植受者中免疫抑制剂他克莫司的药代动力学改变有关，ABC转运蛋白可能参与此类物质的转运，但具体作用尚未阐明。本研究的目的是评估携带不同基因型的肝移植受试者血浆中硫酸吲哚酚和马尿酸的潴留情况，以及探索基因变异是否参与改变微生物衍生毒素与他克莫司药代动力学之间的关系。
纳入接受他克莫司、皮质类固醇和霉酚酸酯免疫抑制方案治疗的肝移植受试者，并分为肾功能正常组和慢性肾脏病组。比较两组携带不同基因型的肝移植受试者血浆中硫酸吲哚酚和马尿酸的浓度。对于有显著差异的基因型携带者，进一步采用Pearson相关系数法研究不同肾功能状态患者血浆硫酸吲哚酚水平与他克莫司剂量校正谷浓度之间的相关性。
rs717620 - 24T变异携带者在肾功能正常的患者中表现出较高的血浆硫酸吲哚酚潴留，此外，慢性肾脏病患者和肾功能正常的患者在正常功能组（β = -0.740，P = 0.020）和功能降低组（β = -0.526，P = 0.005）中硫酸吲哚酚与他克莫司分别呈现出强相关性。
可能是硫酸吲哚酚改变他克莫司药代动力学的途径之一。
