Plasma endotrophin, reflecting tissue fibrosis, is associated with graft failure and mortality in KTRs : results from two prospective cohort studies
© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA..
BACKGROUND: Fibrosis is a suggested cause of graft failure and mortality among kidney transplant recipients (KTRs). Accumulating evidence suggests that collagen type VI is tightly linked to fibrosis and may be a marker of systemic fibrosis and ageing. We studied whether plasma endotrophin, a pro-collagen type VI fragment, is associated with graft failure and mortality among KTRs.
METHODS: In cohort A (57% male, age 53 ± 13 years), we measured plasma endotrophin in 690 prevalent KTRs ≥1 year after transplantation. The non-overlapping cohort B included 500 incident KTRs with serial endotrophin measurements before and after kidney transplantation to assess trajectories and intra-individual variation of endotrophin.
RESULTS: In cohort A, endotrophin was higher in KTRs compared with healthy controls. Concentrations were positively associated with female sex, diabetes, cardiovascular disease, markers of inflammation and kidney injury. Importantly, endotrophin was associated with graft failure {hazard ratio [HR] per doubling 1.87 [95% confidence interval (CI) 1.07-3.28]} and mortality [HR per doubling 2.59 (95% CI 1.73-3.87)] independent of potential confounders. Data from cohort B showed that endotrophin concentrations strongly decrease after transplantation and remain stable during post-transplantation follow-up [intra-individual coefficient of variation 5.0% (95% CI 3.7-7.6)].
CONCLUSIONS: Plasma endotrophin is strongly associated with graft failure and mortality among KTRs. These findings suggest a key role of abnormal extracellular matrix turnover and fibrosis in graft and patient prognosis among KTRs and highlight the need for (interventional) studies targeting the profibrotic state of KTRs. The intra-individual stability after transplantation indicates potential use of endotrophin as a biomarker and outcome measure of fibrosis.
TRIAL REGISTRATION: ClinicalTrials.gov NCT02811835.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
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| Enthalten in: |
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association - 38(2023), 4 vom: 31. März, Seite 1041-1052 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kremer, Daan [VerfasserIn] |
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| Links: |
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| Themen: |
Collagen |
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| Anmerkungen: |
Date Completed 04.04.2023 Date Revised 12.04.2023 published: Print ClinicalTrials.gov: NCT02811835 Citation Status MEDLINE |
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| doi: |
10.1093/ndt/gfac332 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM350474427 |
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| 100 | 1 | |a Kremer, Daan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Plasma endotrophin, reflecting tissue fibrosis, is associated with graft failure and mortality in KTRs |b results from two prospective cohort studies |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Revised 12.04.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT02811835 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2022. Published by Oxford University Press on behalf of the ERA. | ||
| 520 | |a BACKGROUND: Fibrosis is a suggested cause of graft failure and mortality among kidney transplant recipients (KTRs). Accumulating evidence suggests that collagen type VI is tightly linked to fibrosis and may be a marker of systemic fibrosis and ageing. We studied whether plasma endotrophin, a pro-collagen type VI fragment, is associated with graft failure and mortality among KTRs | ||
| 520 | |a METHODS: In cohort A (57% male, age 53 ± 13 years), we measured plasma endotrophin in 690 prevalent KTRs ≥1 year after transplantation. The non-overlapping cohort B included 500 incident KTRs with serial endotrophin measurements before and after kidney transplantation to assess trajectories and intra-individual variation of endotrophin | ||
| 520 | |a RESULTS: In cohort A, endotrophin was higher in KTRs compared with healthy controls. Concentrations were positively associated with female sex, diabetes, cardiovascular disease, markers of inflammation and kidney injury. Importantly, endotrophin was associated with graft failure {hazard ratio [HR] per doubling 1.87 [95% confidence interval (CI) 1.07-3.28]} and mortality [HR per doubling 2.59 (95% CI 1.73-3.87)] independent of potential confounders. Data from cohort B showed that endotrophin concentrations strongly decrease after transplantation and remain stable during post-transplantation follow-up [intra-individual coefficient of variation 5.0% (95% CI 3.7-7.6)] | ||
| 520 | |a CONCLUSIONS: Plasma endotrophin is strongly associated with graft failure and mortality among KTRs. These findings suggest a key role of abnormal extracellular matrix turnover and fibrosis in graft and patient prognosis among KTRs and highlight the need for (interventional) studies targeting the profibrotic state of KTRs. The intra-individual stability after transplantation indicates potential use of endotrophin as a biomarker and outcome measure of fibrosis | ||
| 520 | |a TRIAL REGISTRATION: ClinicalTrials.gov NCT02811835 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 4 | |a fibrosis | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a kidney transplantation | |
| 650 | 4 | |a mortality | |
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| 650 | 7 | |a Collagen Type VI |2 NLM | |
| 700 | 1 | |a Alkaff, Firas F |e verfasserin |4 aut | |
| 700 | 1 | |a Post, Adrian |e verfasserin |4 aut | |
| 700 | 1 | |a Knobbe, Tim J |e verfasserin |4 aut | |
| 700 | 1 | |a Tepel, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Thaunat, Olivier |e verfasserin |4 aut | |
| 700 | 1 | |a Berger, Stefan P |e verfasserin |4 aut | |
| 700 | 1 | |a van den Born, Jacob |e verfasserin |4 aut | |
| 700 | 1 | |a Genovese, Federica |e verfasserin |4 aut | |
| 700 | 1 | |a Karsdal, Morten A |e verfasserin |4 aut | |
| 700 | 1 | |a Rasmussen, Daniel G K |e verfasserin |4 aut | |
| 700 | 1 | |a Bakker, Stephan J L |e verfasserin |4 aut | |
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