TY - JOUR
T1 - Gene expression profiling of the donor kidney at the time of transplantation predicts clinical outcomes 2 years after transplantation
AU - Bodonyi-Kovacs, Gabor
AU - Putheti, Prabhakar
AU - Marino, Miguel
AU - Avihingsanon, Yingyos
AU - Uknis, Marc E.
AU - Monaco, Anthony P.
AU - Strom, Terry B.
AU - Pavlakis, Martha
PY - 2010/5
Y1 - 2010/5
N2 - We have previously demonstrated that biomarkers of inflammation and immune activity detected within intraoperative renal transplant allograft biopsies are linked to adverse short-term post-transplantation clinical outcomes. Now we provide a post hoc analysis of our earlier data in the light of longer clinical follow-up. A total of 75 consecutively performed renal allografts were analyzed for gene expression of proinflammatory molecules, inflammation-induced adhesion molecules, and antiapoptotic genes expressed 15 minutes after vascular reperfusion to determine whether this analysis can aid in predicting long-term quality of renal function, proteinuria, graft loss, and death-censored graft. We have built predictive models for proteinuria (area under the curve = 0.859, p = 0.0001) and graft loss (area under the curve = 0.724, p = 0.027) 2 years post-transplantation using clinical variables in combination with intragraft gene expression data of tumor necrosis factor-α, interleukin-6, CD40, CD3, and tumor necrosis factor-α, Bcl-2, and interferon-γ, respectively. This post hoc analysis demonstrates that hypothesis-driven, targeted polymerase chain reaction profiling of gene expression in the donor kidney at the time of engraftment can predict 2-year post-transplantation clinical outcomes.
AB - We have previously demonstrated that biomarkers of inflammation and immune activity detected within intraoperative renal transplant allograft biopsies are linked to adverse short-term post-transplantation clinical outcomes. Now we provide a post hoc analysis of our earlier data in the light of longer clinical follow-up. A total of 75 consecutively performed renal allografts were analyzed for gene expression of proinflammatory molecules, inflammation-induced adhesion molecules, and antiapoptotic genes expressed 15 minutes after vascular reperfusion to determine whether this analysis can aid in predicting long-term quality of renal function, proteinuria, graft loss, and death-censored graft. We have built predictive models for proteinuria (area under the curve = 0.859, p = 0.0001) and graft loss (area under the curve = 0.724, p = 0.027) 2 years post-transplantation using clinical variables in combination with intragraft gene expression data of tumor necrosis factor-α, interleukin-6, CD40, CD3, and tumor necrosis factor-α, Bcl-2, and interferon-γ, respectively. This post hoc analysis demonstrates that hypothesis-driven, targeted polymerase chain reaction profiling of gene expression in the donor kidney at the time of engraftment can predict 2-year post-transplantation clinical outcomes.
KW - Graft loss
KW - PCR
KW - Prediction
KW - Proteinuria
KW - Renal transplantation
UR - http://www.scopus.com/inward/record.url?scp=77951938139&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77951938139&partnerID=8YFLogxK
U2 - 10.1016/j.humimm.2010.02.013
DO - 10.1016/j.humimm.2010.02.013
M3 - Article
C2 - 20156509
AN - SCOPUS:77951938139
VL - 71
SP - 451
EP - 455
JO - Human Immunology
JF - Human Immunology
SN - 0198-8859
IS - 5
ER -