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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,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
NT11227
MZ0
CEP - Centrální evidence projektů
- MeSH
- analýza hlavních komponent MeSH
- atrofie MeSH
- biopsie MeSH
- imunohistochemie MeSH
- ledvinové kanálky patologie MeSH
- lidé MeSH
- logistické modely MeSH
- nádorové supresorové proteiny analýza genetika MeSH
- neurotrofní faktory analýza genetika MeSH
- opožděný nástup funkce štěpu etiologie metabolismus patologie MeSH
- prospektivní studie MeSH
- regulace genové exprese MeSH
- reperfuzní poškození komplikace MeSH
- transplantace ledvin škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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.
Citace poskytuje 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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