Impaired metabolism in donor kidney grafts after steroid pretreatment.
Summary We recently showed in a randomized control trial that steroid pretreatment of the deceased organ donor suppressed inflammation in the transplant organ but did not reduce the rate or duration of delayed graft function (DGF). This study sought to elucidate such of those factors that caused DGF in the steroid-treated subjects. Genome-wide gene expression profiles were used from 20 steroid-pretreated donor-organs and were analyzed on the level of regulatory protein-protein interaction networks. Significance analysis of microarrays (SAM) yielded 63 significantly down-regulated sequences associated with DGF that could be functionally categorized according to Protein ANalysis THrough Evolutionary Relationships ontologies into two main biologic processes: transport (P < 0.001) and metabolism (P < 0.001). The identified genes suggest hypoxia as the cause of DGF, which cannot be counterbalanced by steroid treatment. Our data showed that molecular pathways affected by ischemia such as transport and metabolism are associated with DGF. Potential interventional targeted therapy based on these findings includes peroxisome proliferator-activated receptor agonists or caspase inhibitors.
Wilflingseder
Julia
J
Department of Nephrology KH Elisabethinen, Linz, Austria.
Kainz
Alexander
A
Mühlberger
Irmgard
I
Perco
Paul
P
Langer
Robert
R
Kristo
Ivan
I
Mayer
Bernd
B
Oberbauer
Rainer
R
D000368:Aged; D001706:Biopsy; D019295:Computational Biology / Q000706:statistics & numerical data; D051799:Delayed Graft Function / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data*; D006801:Humans; D000860:Hypoxia / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation / Q000706:statistics & numerical data*; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012307:Risk Factors; D013256:Steroids / Q000008:administration & dosage / Q000009:adverse effects*; D014019:Tissue Donors / Q000706:statistics & numerical data
D013256:Steroids