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Tubular atrophy and low netrin-1 gene expression are associated with delayed kidney allograft function
M. Wohlfahrtova, I. Brabcova, F. Zelezny, P. Balaz, L. Janousek, E. Honsova, A. Lodererova, P. Wohlfahrt, O. Viklicky,
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
NT11227
MZ0
CEP Register
- MeSH
- Principal Component Analysis MeSH
- Atrophy MeSH
- Biopsy MeSH
- Immunohistochemistry MeSH
- Kidney Tubules pathology MeSH
- Humans MeSH
- Logistic Models MeSH
- Tumor Suppressor Proteins analysis genetics MeSH
- Nerve Growth Factors analysis genetics MeSH
- Delayed Graft Function etiology metabolism pathology MeSH
- Prospective Studies MeSH
- Gene Expression Regulation MeSH
- Reperfusion Injury complications MeSH
- Kidney Transplantation adverse effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Delayed graft function (DGF) caused by ischemia/reperfusion injury (I/RI) negatively influences the outcome of kidney transplantation. This prospective single-center study characterized the intrarenal transcriptome during I/RI as a means of identifying genes associated with DGF development. METHODS: Characterization of the intrarenal transcription profile associated with I/RI was carried out on three sequential graft biopsies from respective allografts before and during transplantation. The intragraft expression of 92 candidate genes was measured using quantitative real-time reverse transcriptase polymerase chain reaction (2) in delayed (n=9) and primary function allografts (n=26). RESULTS: Cold storage was not associated with significant changes to the expression profile of the target gene transcripts; however, up-regulation of 16 genes associated with enhanced activation of innate and adaptive immune responses and apoptosis was observed after reperfusion. Multivariate logistic regression analysis revealed that higher tubular atrophy scores (ct) together with a lower expression of Netrin-1 might predict DGF development (training area under the receiver operating curve=0.89, cross-validated area under the receiver operating curve=0.81). CONCLUSIONS: Poor baseline tubular cell quality (defined by a higher rate of tubular atrophy) combined with the reduced potential of apoptotic survival factors represented by decreased Netrin-1 gene expression were associated with delayed kidney graft function.
References provided by Crossref.org
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- $a Wohlfahrtová, Mariana $u 1 Department of Nephrology, Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 2 Transplant Laboratory, Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 3 Department of Cybernetics, Faculty of Electrical Engineering, Czech Technical University, Prague, Czech Republic. 4 Department of Transplant Surgery, Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 5 Clinical and Transplant Pathology Department, Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 6 Address correspondence to: Ondrej Viklicky, M.D., Ph.D., Department of Nephrology, Transplant Center, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 14021 Prague, Czech Republic. $7 xx0166862
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- $a BACKGROUND: Delayed graft function (DGF) caused by ischemia/reperfusion injury (I/RI) negatively influences the outcome of kidney transplantation. This prospective single-center study characterized the intrarenal transcriptome during I/RI as a means of identifying genes associated with DGF development. METHODS: Characterization of the intrarenal transcription profile associated with I/RI was carried out on three sequential graft biopsies from respective allografts before and during transplantation. The intragraft expression of 92 candidate genes was measured using quantitative real-time reverse transcriptase polymerase chain reaction (2) in delayed (n=9) and primary function allografts (n=26). RESULTS: Cold storage was not associated with significant changes to the expression profile of the target gene transcripts; however, up-regulation of 16 genes associated with enhanced activation of innate and adaptive immune responses and apoptosis was observed after reperfusion. Multivariate logistic regression analysis revealed that higher tubular atrophy scores (ct) together with a lower expression of Netrin-1 might predict DGF development (training area under the receiver operating curve=0.89, cross-validated area under the receiver operating curve=0.81). CONCLUSIONS: Poor baseline tubular cell quality (defined by a higher rate of tubular atrophy) combined with the reduced potential of apoptotic survival factors represented by decreased Netrin-1 gene expression were associated with delayed kidney graft function.
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