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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Frontiers Media S.A.
2025-05-01
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| 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. |
| format | Article |
| id | doaj-art-e70fb13cb2924ea59650325ccba8656b |
| institution | OA Journals |
| issn | 1432-2277 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Transplant International |
| 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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