Metabolomic and proteomic analyses of renal function after liver transplantation

BackgroundRenal 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...

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Main Authors: Xiaoling Wang, Nadja Grobe, Barbara Franchin, Josh Levitsky, Paolo Cravedi, Peter Kotanko
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Transplantation
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Online Access:https://www.frontiersin.org/articles/10.3389/frtra.2025.1572852/full
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author Xiaoling Wang
Nadja Grobe
Barbara Franchin
Josh Levitsky
Paolo Cravedi
Peter Kotanko
Peter Kotanko
author_facet Xiaoling Wang
Nadja Grobe
Barbara Franchin
Josh Levitsky
Paolo Cravedi
Peter Kotanko
Peter Kotanko
author_sort Xiaoling Wang
collection DOAJ
description BackgroundRenal 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.MethodsNine 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.ResultsMetabolomic 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.ConclusionThis 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.
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spelling doaj-art-5cefcd6bd07146359b5131b4655122062025-08-20T03:53:42ZengFrontiers Media S.A.Frontiers in Transplantation2813-24402025-04-01410.3389/frtra.2025.15728521572852Metabolomic and proteomic analyses of renal function after liver transplantationXiaoling Wang0Nadja Grobe1Barbara Franchin2Josh Levitsky3Paolo Cravedi4Peter Kotanko5Peter Kotanko6Basic and Applied Laboratory Sciences, Renal Research Institute, New York, NY, United StatesBasic and Applied Laboratory Sciences, Renal Research Institute, New York, NY, United StatesTranslational Transplant Research Center (TTRC), Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDivision of Gastroenterology and Hepatology, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, United StatesTranslational Transplant Research Center (TTRC), Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesBasic and Applied Laboratory Sciences, Renal Research Institute, New York, NY, United StatesTranslational Transplant Research Center (TTRC), Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesBackgroundRenal 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.MethodsNine 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.ResultsMetabolomic 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.ConclusionThis 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.https://www.frontiersin.org/articles/10.3389/frtra.2025.1572852/fullliver transplantationrenal dysfunctionmetabolomicsproteomicsmass spectrometry
spellingShingle Xiaoling Wang
Nadja Grobe
Barbara Franchin
Josh Levitsky
Paolo Cravedi
Peter Kotanko
Peter Kotanko
Metabolomic and proteomic analyses of renal function after liver transplantation
Frontiers in Transplantation
liver transplantation
renal dysfunction
metabolomics
proteomics
mass spectrometry
title Metabolomic and proteomic analyses of renal function after liver transplantation
title_full Metabolomic and proteomic analyses of renal function after liver transplantation
title_fullStr Metabolomic and proteomic analyses of renal function after liver transplantation
title_full_unstemmed Metabolomic and proteomic analyses of renal function after liver transplantation
title_short Metabolomic and proteomic analyses of renal function after liver transplantation
title_sort metabolomic and proteomic analyses of renal function after liver transplantation
topic liver transplantation
renal dysfunction
metabolomics
proteomics
mass spectrometry
url https://www.frontiersin.org/articles/10.3389/frtra.2025.1572852/full
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