title: The transcriptome of the implant biopsy identifies donor kidneys at increased risk of delayed graft function.
abstract: Improved assessment of donor organ quality at time of transplantation would help in management of potentially usable organs. The transcriptome might correlate with risk of delayed graft function (DGF) better than conventional risk factors. Microarray results of 87 consecutive implantation biopsies taken postreperfusion in 42 deceased (DD) and 45 living (LD) donor kidneys were compared to clinical and histopathology-based scores. Unsupervised analysis separated the 87 kidneys into three groups: LD, DD1 and DD2. Kidneys in DD2 had a greater incidence of DGF (38.1 vs. 9.5%, p < 0.05) than those in DD1. Clinical and histopathological risk scores did not discriminate DD1 from DD2. A total of 1051 transcripts were differentially expressed between DD1 and DD2, but no transcripts separated DGF from immediate graft function (adjusted p < 0.01). Principal components analysis revealed a continuum from LD to DD1 to DD2, i.e. from best to poorest functioning kidneys. Within DD kidneys, the odds ratio for DGF was significantly increased with a transcriptome-based score and recipient age (p < 0.03) but not with clinical or histopathologic scores. The transcriptome reflects kidney quality and susceptibility to DGF better than available clinical and histopathological scoring systems.
authors.affiliation: Division of Nephrology and Transplantation Immunology, Department of Medicine, University of Alberta, Edmonton, AB, Canada. tmueller@ualberta.ca
authors.forename: T F
authors.initials: TF
authors.lastname: Mueller
authors.forename: J
authors.initials: J
authors.lastname: Reeve
authors.forename: G S
authors.initials: GS
authors.lastname: Jhangri
authors.forename: M
authors.initials: M
authors.lastname: Mengel
authors.forename: Z
authors.initials: Z
authors.lastname: Jacaj
authors.forename: L
authors.initials: L
authors.lastname: Cairo
authors.forename: M
authors.initials: M
authors.lastname: Obeidat
authors.forename: G
authors.initials: G
authors.lastname: Todd
authors.forename: R
authors.initials: R
authors.lastname: Moore
authors.forename: K S
authors.initials: KS
authors.lastname: Famulski
authors.forename: J
authors.initials: J
authors.lastname: Cruz
authors.forename: D
authors.initials: D
authors.lastname: Wishart
authors.forename: C
authors.initials: C
authors.lastname: Meng
authors.forename: B
authors.initials: B
authors.lastname: Sis
authors.forename: K
authors.initials: K
authors.lastname: Solez
authors.forename: B
authors.initials: B
authors.lastname: Kaplan
authors.forename: P F
authors.initials: PF
authors.lastname: Halloran
mesh_terms: D001706:Biopsy; D002102:Cadaver; D051799:Delayed Graft Function / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D014019:Tissue Donors