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Dickkopf 3—A New Indicator for the Deterioration of Allograft Function After Kidney Transplantation

Evidence of tubular atrophy and interstitial fibrosis is prognostically unfavorable and associated with a premature graft loss after kidney transplantation. Recently, Dickkopf 3 (DKK3), a profibrotic glycoprotein released by stressed tubular epithelial cells, has been identified to cause IF/TA by re...

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Autores principales: Schuster, Antonia, Steines, Louisa, Müller, Karolina, Zeman, Florian, Findeisen, Peter, Banas, Bernhard, Bergler, Tobias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130628/
https://www.ncbi.nlm.nih.gov/pubmed/35646976
http://dx.doi.org/10.3389/fmed.2022.885018
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author Schuster, Antonia
Steines, Louisa
Müller, Karolina
Zeman, Florian
Findeisen, Peter
Banas, Bernhard
Bergler, Tobias
author_facet Schuster, Antonia
Steines, Louisa
Müller, Karolina
Zeman, Florian
Findeisen, Peter
Banas, Bernhard
Bergler, Tobias
author_sort Schuster, Antonia
collection PubMed
description Evidence of tubular atrophy and interstitial fibrosis is prognostically unfavorable and associated with a premature graft loss after kidney transplantation. Recently, Dickkopf 3 (DKK3), a profibrotic glycoprotein released by stressed tubular epithelial cells, has been identified to cause IF/TA by regulating the Wnt/β-catenin signaling and seems to engage a T-cell response. The aim of our study was to determine if a correlation between DKK3 and graft function exists and if DKK3 could be a new indicator to identify patients at risk for a deterioration in graft function. Patients, transplanted between 2016 and 2018, were analyzed with regard to DKK3 in the urine and graft function (creatinine, eGFR, albuminuria). Multivariable analyzes were used including known factors influencing graft function (PRA, donor age) to stress robustness of DKK3. The 3 and 12 month DKK3 values were significant predictors for subsequent graft function up to 36 months. An increase of DKK3 from month 3 to 12 of ≥ 25% showed a higher risk of an impaired graft function, with, e.g., a reduction in eGFR of about 9–10 ml/min in contrast to patients without intensified DKK3 increase. Induction therapy has an influence on DKK3 as patients induced with a T-cell depleting therapy showed a trend toward lower DKK3 values. In summary, our study is the first investigation of DKK3 in kidney transplant recipients and was able to show that DKK3 could forecast graft function. It is recommended to investigate the potential of DKK3 as a predictor of kidney function after transplantation in further studies.
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spelling pubmed-91306282022-05-26 Dickkopf 3—A New Indicator for the Deterioration of Allograft Function After Kidney Transplantation Schuster, Antonia Steines, Louisa Müller, Karolina Zeman, Florian Findeisen, Peter Banas, Bernhard Bergler, Tobias Front Med (Lausanne) Medicine Evidence of tubular atrophy and interstitial fibrosis is prognostically unfavorable and associated with a premature graft loss after kidney transplantation. Recently, Dickkopf 3 (DKK3), a profibrotic glycoprotein released by stressed tubular epithelial cells, has been identified to cause IF/TA by regulating the Wnt/β-catenin signaling and seems to engage a T-cell response. The aim of our study was to determine if a correlation between DKK3 and graft function exists and if DKK3 could be a new indicator to identify patients at risk for a deterioration in graft function. Patients, transplanted between 2016 and 2018, were analyzed with regard to DKK3 in the urine and graft function (creatinine, eGFR, albuminuria). Multivariable analyzes were used including known factors influencing graft function (PRA, donor age) to stress robustness of DKK3. The 3 and 12 month DKK3 values were significant predictors for subsequent graft function up to 36 months. An increase of DKK3 from month 3 to 12 of ≥ 25% showed a higher risk of an impaired graft function, with, e.g., a reduction in eGFR of about 9–10 ml/min in contrast to patients without intensified DKK3 increase. Induction therapy has an influence on DKK3 as patients induced with a T-cell depleting therapy showed a trend toward lower DKK3 values. In summary, our study is the first investigation of DKK3 in kidney transplant recipients and was able to show that DKK3 could forecast graft function. It is recommended to investigate the potential of DKK3 as a predictor of kidney function after transplantation in further studies. Frontiers Media S.A. 2022-05-11 /pmc/articles/PMC9130628/ /pubmed/35646976 http://dx.doi.org/10.3389/fmed.2022.885018 Text en Copyright © 2022 Schuster, Steines, Müller, Zeman, Findeisen, Banas and Bergler. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Schuster, Antonia
Steines, Louisa
Müller, Karolina
Zeman, Florian
Findeisen, Peter
Banas, Bernhard
Bergler, Tobias
Dickkopf 3—A New Indicator for the Deterioration of Allograft Function After Kidney Transplantation
title Dickkopf 3—A New Indicator for the Deterioration of Allograft Function After Kidney Transplantation
title_full Dickkopf 3—A New Indicator for the Deterioration of Allograft Function After Kidney Transplantation
title_fullStr Dickkopf 3—A New Indicator for the Deterioration of Allograft Function After Kidney Transplantation
title_full_unstemmed Dickkopf 3—A New Indicator for the Deterioration of Allograft Function After Kidney Transplantation
title_short Dickkopf 3—A New Indicator for the Deterioration of Allograft Function After Kidney Transplantation
title_sort dickkopf 3—a new indicator for the deterioration of allograft function after kidney transplantation
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130628/
https://www.ncbi.nlm.nih.gov/pubmed/35646976
http://dx.doi.org/10.3389/fmed.2022.885018
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