Metabolomic and proteomic analyses of renal function after liver transplantation.

Frontiers in transplantation Pub Date : 2025-04-29 eCollection Date: 2025-01-01 DOI:10.3389/frtra.2025.1572852
Xiaoling Wang, Nadja Grobe, Barbara Franchin, Josh Levitsky, Paolo Cravedi, Peter Kotanko
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Abstract

Background: Renal dysfunction is a common and serious complication in patients with end-stage liver diseases. While some patients recover renal function after liver transplantation (LT), others do not. Additionally, patients with normal kidney function (Normal-KF) before LT may develop post-transplant renal dysfunction. Early identification of patients at risk for impaired kidney function (Impaired-KF) post-LT is critical to improving outcomes. This study integrated metabolomic and proteomic analyses to investigate molecular profiles distinguishing Normal-KF from Impaired-KF post-LT.

Methods: Nine LT recipients were classified into Normal-KF (n = 5) and Impaired-KF (n = 4) groups. One additional recipient with pre-transplant renal function impairment who recovered renal function after LT, was analyzed separately. Serum samples were collected at 2- and 5-weeks post-LT. The metabolomic and proteomic profiles were assessed by untargeted liquid chromatography-tandem mass spectrometry.

Results: Metabolomic analysis identified 29 significantly altered metabolites between Normal-KF and Impaired-KF (fold change > 2, p < 0.05). Proteomic analysis revealed 45 differentially expressed proteins (fold change > 1.25, p < 0.05). For the recovered patient, the metabolomic profile closely resembled Normal-KF, whereas the proteomic profile remained aligned with Impaired-KF at both 14- and 35-days post-LT. From week 2 to week 5, both the metabolomic and proteomic profiles of the recovered patient showed trends toward the Normal-KF.

Conclusion: This study revealed distinct metabolomic and proteomic signatures associated with renal dysfunction post-LT. Proteomic profiles indicated a delayed recovery compared to metabolomic profiles, suggesting a dynamic and muti-layered renal recovery process. Further research is warranted to elucidate the functional implications of the differential proteins and metabolites for improved monitoring and therapeutic strategies.

肝移植术后肾功能的代谢组学和蛋白质组学分析。
背景:肾功能不全是终末期肝病患者常见且严重的并发症。虽然一些患者在肝移植(LT)后恢复肾功能,但另一些患者则没有。此外,移植前肾功能正常(normal - kf)的患者可能出现移植后肾功能不全。早期识别肾移植后存在肾功能受损风险的患者对于改善预后至关重要。这项研究结合了代谢组学和蛋白质组学分析来研究区分lt后正常kf和受损kf的分子图谱。方法:9例肝移植受者分为kf正常组(n = 5)和kf受损组(n = 4)。另一名移植前肾功能受损的肾移植后肾功能恢复的受者单独进行了分析。分别于术后2周和5周采集血清样本。代谢组学和蛋白质组学分析采用非靶向液相色谱-串联质谱法。结果:代谢组学分析发现,在正常kf和受损kf之间,有29种代谢物发生了显著改变(fold change bbbb2, p . 1.25, p)。结论:该研究揭示了与肾移植后肾功能障碍相关的独特代谢组学和蛋白质组学特征。蛋白质组学分析表明,与代谢组学分析相比,肾脏恢复延迟,表明肾脏恢复是一个动态的、多层次的过程。进一步的研究需要阐明差异蛋白和代谢物的功能意义,以改善监测和治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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