BACKGROUND: Delayed graft function (DGF) after kidney transplantation (KTx) ranges between 2% and 50%. The mechanisms leading to DGF deserve special interest because DGF exerts negative influences on long-term outcomes. We studied gene expression profiles in deceased donor kidney (DDK) biopsies with and without DGF. METHODS: Gene expression profiling was performed on donor kidney tissues from 33 DDK with the use of microarrays. DDK were classified as grafts with immediate function (non-DGF; n=21) and grafts with DGF (n=12). DGF was defined as a dialysis requirement in the first week after transplantation. Demographic donor and recipient information was collected. The robust-multiarray average method was used to estimate probe set expression summaries. Logistic regression was used to identify genes significantly associated with DGF development. RESULTS: Patients were followed for 3 months after KTx. Thirty-eight probe sets (n=36 genes) were univariably differentially expressed in DDK with DGF when compared with DDK with non-DGF (alpha=0.001). Sixty-nine probe sets (n=65 genes) were differentially expressed in DDK with DGF when compared with DDK with non-DGF after adjusting for cold ischemia time (alpha=0.001). Gene ontology terms classified the overexpressed genes in DDK with DGF as principally related to cell cycle/growth (e.g., IGFBP5, CSNK2A2), signal transduction (e.g., RASGRP3), immune response (e.g., CD83, BCL3, MX1), and metabolism (e.g., ENPP4, GBA3). TNFRSF1B was overexpressed in DDK with DGF. CONCLUSIONS: Cold ischemia time was a predictor of DGF independently of the preservation method. We identified a set of 36 genes candidates of DGF in DDK, with genes involved in the inflammatory response being the more important.
BACKGROUND: Delayed graft function (DGF) after kidney transplantation (KTx) ranges between 2% and 50%. The mechanisms leading to DGF deserve special interest because DGF exerts negative influences on long-term outcomes. We studied gene expression profiles in deceased donor kidney (DDK) biopsies with and without DGF. METHODS: Gene expression profiling was performed on donor kidney tissues from 33 DDK with the use of microarrays. DDK were classified as grafts with immediate function (non-DGF; n=21) and grafts with DGF (n=12). DGF was defined as a dialysis requirement in the first week after transplantation. Demographic donor and recipient information was collected. The robust-multiarray average method was used to estimate probe set expression summaries. Logistic regression was used to identify genes significantly associated with DGF development. RESULTS:Patients were followed for 3 months after KTx. Thirty-eight probe sets (n=36 genes) were univariably differentially expressed in DDK with DGF when compared with DDK with non-DGF (alpha=0.001). Sixty-nine probe sets (n=65 genes) were differentially expressed in DDK with DGF when compared with DDK with non-DGF after adjusting for cold ischemia time (alpha=0.001). Gene ontology terms classified the overexpressed genes in DDK with DGF as principally related to cell cycle/growth (e.g., IGFBP5, CSNK2A2), signal transduction (e.g., RASGRP3), immune response (e.g., CD83, BCL3, MX1), and metabolism (e.g., ENPP4, GBA3). TNFRSF1B was overexpressed in DDK with DGF. CONCLUSIONS: Cold ischemia time was a predictor of DGF independently of the preservation method. We identified a set of 36 genes candidates of DGF in DDK, with genes involved in the inflammatory response being the more important.
Authors: Konrad S Famulski; Declan G de Freitas; Chatchai Kreepala; Jessica Chang; Joana Sellares; Banu Sis; Gunilla Einecke; Michael Mengel; Jeff Reeve; Philip F Halloran Journal: J Am Soc Nephrol Date: 2012-02-16 Impact factor: 10.121
Authors: Valeria R Mas; Mariano J Scian; Kellie J Archer; Jihee L Suh; Krystle G David; Qing Ren; Todd W B Gehr; Anne L King; Marc P Posner; Thomas F Mueller; Daniel G Maluf Journal: Mol Med Date: 2011-09-06 Impact factor: 6.354
Authors: Insa M Schmidt; Isaac E Hall; Sujata Kale; Sik Lee; Chuan-Hua He; Yashang Lee; Geoffrey L Chupp; Gilbert W Moeckel; Chun Geun Lee; Jack A Elias; Chirag R Parikh; Lloyd G Cantley Journal: J Am Soc Nephrol Date: 2013-01-04 Impact factor: 10.121