Proenkephalin A 119-159 in Kidney Transplantation: A Novel Biomarker for Superior Tracking of Graft Function Trajectories

Accurate assessment of graft function trajectories after kidney transplantation is essential for optimizing patient management. Slow graft function (SGF) and delayed graft function (DGF) are associated with impaired recovery, yet current diagnostic tools lack granularity for timely risk stratificati...

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Main Authors: Louise Benning, Marvin Reineke, Camila Eleuterio Rodrigues, Florian Kälble, Claudius Speer, Claudia Sommerer, Christoph F. Mahler, Felix C. F. Schmitt, Markus Mieth, Martin Zeier, Christoph Michalski, Arianeb Mehrabi, Oliver Hartmann, Markus Zorn, Sophie C. Anker, David Czock, Markus A. Weigand, Zoltan Endre, Christian Morath, Christian Nusshag
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Transplant International
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Online Access:https://www.frontierspartnerships.org/articles/10.3389/ti.2025.14366/full
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author Louise Benning
Marvin Reineke
Camila Eleuterio Rodrigues
Camila Eleuterio Rodrigues
Florian Kälble
Claudius Speer
Claudia Sommerer
Christoph F. Mahler
Felix C. F. Schmitt
Markus Mieth
Martin Zeier
Christoph Michalski
Arianeb Mehrabi
Oliver Hartmann
Markus Zorn
Sophie C. Anker
David Czock
Markus A. Weigand
Zoltan Endre
Christian Morath
Christian Nusshag
author_facet Louise Benning
Marvin Reineke
Camila Eleuterio Rodrigues
Camila Eleuterio Rodrigues
Florian Kälble
Claudius Speer
Claudia Sommerer
Christoph F. Mahler
Felix C. F. Schmitt
Markus Mieth
Martin Zeier
Christoph Michalski
Arianeb Mehrabi
Oliver Hartmann
Markus Zorn
Sophie C. Anker
David Czock
Markus A. Weigand
Zoltan Endre
Christian Morath
Christian Nusshag
author_sort Louise Benning
collection DOAJ
description Accurate assessment of graft function trajectories after kidney transplantation is essential for optimizing patient management. Slow graft function (SGF) and delayed graft function (DGF) are associated with impaired recovery, yet current diagnostic tools lack granularity for timely risk stratification. Proenkephalin A 119-159 (penKid) may improve graft function assessment, enhancing risk stratification for SGF, DGF, and associated outcomes. This prospective study evaluated 159 kidney transplant recipients at Heidelberg University Hospital to compare plasma penKid levels with current risk-indicators for poor (functional) graft trajectories. Validation was conducted using an independent transplant cohort from Sydney. Clinical relevance of biomarker-indicated changes in graft function was assessed using multivariable regression models and AUROC analyses. From day one post-transplant, penKid outperformed serum creatinine (SCr) in identifying functional trajectories associated with DGF (AUROC penKid: 0.87 vs. SCr: 0.56) and differentiated SGF from DGF (AUROC penKid: 0.79 vs. SCr: 0.33) up to eight days earlier. PenKid further demonstrated superior granularity in assessing DGF severity and 30-day outcomes. After adjustment for common risk factors, penKid remained the strongest risk stratifier for all tested outcomes. PenKid is a superior biomarker for earlier assessment of graft function trajectories, offering potential to enhance personalized care and clinical trial designs in kidney transplantation.
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spelling doaj-art-e70fb13cb2924ea59650325ccba8656b2025-08-20T02:25:47ZengFrontiers Media S.A.Transplant International1432-22772025-05-013810.3389/ti.2025.1436614366Proenkephalin A 119-159 in Kidney Transplantation: A Novel Biomarker for Superior Tracking of Graft Function TrajectoriesLouise Benning0Marvin Reineke1Camila Eleuterio Rodrigues2Camila Eleuterio Rodrigues3Florian Kälble4Claudius Speer5Claudia Sommerer6Christoph F. Mahler7Felix C. F. Schmitt8Markus Mieth9Martin Zeier10Christoph Michalski11Arianeb Mehrabi12Oliver Hartmann13Markus Zorn14Sophie C. Anker15David Czock16Markus A. Weigand17Zoltan Endre18Christian Morath19Christian Nusshag20Department of Nephrology, Heidelberg University Hospital, Medical Faculty, Heidelberg University, Heidelberg, GermanyDepartment of Nephrology, Heidelberg University Hospital, Medical Faculty, Heidelberg University, Heidelberg, GermanyDepartment of Nephrology, Prince of Wales Hospital, Sydney, NSW, AustraliaDepartment of Nephrology, Hospital das Clínicas - University of São Paulo School of Medicine, São Paulo, BrazilDepartment of Nephrology, Heidelberg University Hospital, Medical Faculty, Heidelberg University, Heidelberg, GermanyDepartment of Nephrology, Heidelberg University Hospital, Medical Faculty, Heidelberg University, Heidelberg, GermanyDepartment of Nephrology, Heidelberg University Hospital, Medical Faculty, Heidelberg University, Heidelberg, GermanyDepartment of Nephrology, Heidelberg University Hospital, Medical Faculty, Heidelberg University, Heidelberg, GermanyDepartment of Anaesthesiology, Heidelberg University Hospital, Medical Faculty, Heidelberg University, Heidelberg, GermanyDepartment of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Medical Faculty, Heidelberg University, Heidelberg, GermanyDepartment of Nephrology, Heidelberg University Hospital, Medical Faculty, Heidelberg University, Heidelberg, GermanyDepartment of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Medical Faculty, Heidelberg University, Heidelberg, GermanyDepartment of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Medical Faculty, Heidelberg University, Heidelberg, GermanySphingoTec GmbH, Berlin, GermanyCentral Laboratory of University Hospital Heidelberg, Department of Endocrinology and Metabolism, Heidelberg University Hospital, Medical Faculty, Heidelberg University, Heidelberg, GermanyCentral Laboratory of University Hospital Heidelberg, Department of Endocrinology and Metabolism, Heidelberg University Hospital, Medical Faculty, Heidelberg University, Heidelberg, GermanyDepartment of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Medical Faculty, Heidelberg University, Heidelberg, GermanyDepartment of Anaesthesiology, Heidelberg University Hospital, Medical Faculty, Heidelberg University, Heidelberg, GermanyDepartment of Nephrology, Prince of Wales Hospital, Sydney, NSW, AustraliaDepartment of Nephrology, Heidelberg University Hospital, Medical Faculty, Heidelberg University, Heidelberg, GermanyDepartment of Nephrology, Heidelberg University Hospital, Medical Faculty, Heidelberg University, Heidelberg, GermanyAccurate assessment of graft function trajectories after kidney transplantation is essential for optimizing patient management. Slow graft function (SGF) and delayed graft function (DGF) are associated with impaired recovery, yet current diagnostic tools lack granularity for timely risk stratification. Proenkephalin A 119-159 (penKid) may improve graft function assessment, enhancing risk stratification for SGF, DGF, and associated outcomes. This prospective study evaluated 159 kidney transplant recipients at Heidelberg University Hospital to compare plasma penKid levels with current risk-indicators for poor (functional) graft trajectories. Validation was conducted using an independent transplant cohort from Sydney. Clinical relevance of biomarker-indicated changes in graft function was assessed using multivariable regression models and AUROC analyses. From day one post-transplant, penKid outperformed serum creatinine (SCr) in identifying functional trajectories associated with DGF (AUROC penKid: 0.87 vs. SCr: 0.56) and differentiated SGF from DGF (AUROC penKid: 0.79 vs. SCr: 0.33) up to eight days earlier. PenKid further demonstrated superior granularity in assessing DGF severity and 30-day outcomes. After adjustment for common risk factors, penKid remained the strongest risk stratifier for all tested outcomes. PenKid is a superior biomarker for earlier assessment of graft function trajectories, offering potential to enhance personalized care and clinical trial designs in kidney transplantation.https://www.frontierspartnerships.org/articles/10.3389/ti.2025.14366/fulldelayed graft functionproenkephalin Arisk stratificationgraft function trajectorystudy enrichmentslow graft function
spellingShingle Louise Benning
Marvin Reineke
Camila Eleuterio Rodrigues
Camila Eleuterio Rodrigues
Florian Kälble
Claudius Speer
Claudia Sommerer
Christoph F. Mahler
Felix C. F. Schmitt
Markus Mieth
Martin Zeier
Christoph Michalski
Arianeb Mehrabi
Oliver Hartmann
Markus Zorn
Sophie C. Anker
David Czock
Markus A. Weigand
Zoltan Endre
Christian Morath
Christian Nusshag
Proenkephalin A 119-159 in Kidney Transplantation: A Novel Biomarker for Superior Tracking of Graft Function Trajectories
Transplant International
delayed graft function
proenkephalin A
risk stratification
graft function trajectory
study enrichment
slow graft function
title Proenkephalin A 119-159 in Kidney Transplantation: A Novel Biomarker for Superior Tracking of Graft Function Trajectories
title_full Proenkephalin A 119-159 in Kidney Transplantation: A Novel Biomarker for Superior Tracking of Graft Function Trajectories
title_fullStr Proenkephalin A 119-159 in Kidney Transplantation: A Novel Biomarker for Superior Tracking of Graft Function Trajectories
title_full_unstemmed Proenkephalin A 119-159 in Kidney Transplantation: A Novel Biomarker for Superior Tracking of Graft Function Trajectories
title_short Proenkephalin A 119-159 in Kidney Transplantation: A Novel Biomarker for Superior Tracking of Graft Function Trajectories
title_sort proenkephalin a 119 159 in kidney transplantation a novel biomarker for superior tracking of graft function trajectories
topic delayed graft function
proenkephalin A
risk stratification
graft function trajectory
study enrichment
slow graft function
url https://www.frontierspartnerships.org/articles/10.3389/ti.2025.14366/full
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