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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Frontiers Media S.A.
2022-05-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.885018/full |
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| author | Antonia Schuster Louisa Steines Karolina Müller Florian Zeman Peter Findeisen Bernhard Banas Tobias Bergler |
| author_facet | Antonia Schuster Louisa Steines Karolina Müller Florian Zeman Peter Findeisen Bernhard Banas Tobias Bergler |
| author_sort | Antonia Schuster |
| collection | DOAJ |
| 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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| id | doaj.art-efb43aecd4a34802b0095adad592e528 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-12T21:18:57Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-efb43aecd4a34802b0095adad592e5282022-12-22T00:11:40ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-05-01910.3389/fmed.2022.885018885018Dickkopf 3—A New Indicator for the Deterioration of Allograft Function After Kidney TransplantationAntonia Schuster0Louisa Steines1Karolina Müller2Florian Zeman3Peter Findeisen4Bernhard Banas5Tobias Bergler6Department of Nephrology, University Hospital Regensburg, Regensburg, GermanyDepartment of Nephrology, University Hospital Regensburg, Regensburg, GermanyCenter for Clinical Studies, University Hospital Regensburg, Regensburg, GermanyCenter for Clinical Studies, University Hospital Regensburg, Regensburg, GermanyMVZ Laboratory Dr. Limbach, Heidelberg, GermanyDepartment of Nephrology, University Hospital Regensburg, Regensburg, GermanyDepartment of Nephrology, University Hospital Regensburg, Regensburg, GermanyEvidence 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.https://www.frontiersin.org/articles/10.3389/fmed.2022.885018/fullkidney transplantationallograft survivalDickkopf (DKK)albuminuriaglomerular filtration rate |
| spellingShingle | Antonia Schuster Louisa Steines Karolina Müller Florian Zeman Peter Findeisen Bernhard Banas Tobias Bergler Dickkopf 3—A New Indicator for the Deterioration of Allograft Function After Kidney Transplantation Frontiers in Medicine kidney transplantation allograft survival Dickkopf (DKK) albuminuria glomerular filtration rate |
| 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 | kidney transplantation allograft survival Dickkopf (DKK) albuminuria glomerular filtration rate |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.885018/full |
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