title: Pretransplant transcriptome profiles identify among kidneys with delayed graft function those with poorer quality and outcome.
abstract: Robust biomarkers are needed to identify donor kidneys with poor quality associated with inferior early and longer-term outcome. The occurrence of delayed graft function (DGF) is most often used as a clinical outcome marker to capture poor kidney quality. Gene expression profiles of 92 preimplantation biopsies were evaluated in relation to DGF and estimated glomerular filtration rate (eGFR) to identify preoperative gene transcript changes associated with short-term function. Patients were stratified into those who required dialysis during the first week (DGF group) versus those without (noDGF group) and subclassified according to 1-month eGFR of >45 mL/min (eGFR(hi)) versus eGFR of ≤45 mL/min (eGFR(lo)). The groups and subgroups were compared in relation to clinical donor and recipient variables and transcriptome-associated biological pathways. A validation set was used to confirm target genes. Donor and recipient characteristics were similar between the DGF versus noDGF groups. A total of 206 probe sets were significant between groups (P < 0.01), but the gene functional analyses failed to identify any significantly affected pathways. However, the subclassification of the DGF and noDGF groups identified 283 probe sets to be significant among groups and associated with biological pathways. Kidneys that developed postoperative DGF and sustained an impaired 1-month function (DGF(lo) group) showed a transcriptome profile of significant immune activation already preimplant. In addition, these kidneys maintained a poorer transplant function throughout the first-year posttransplant. In conclusion, DGF is a poor marker for organ quality and transplant outcome. In contrast, preimplant gene expression profiles identify "poor quality" grafts and may eventually improve organ allocation.
authors.affiliation: Department of Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, Virginia, United States of America. vmas@mcvh-vcu.edu
authors.forename: Valeria R
authors.initials: VR
authors.lastname: Mas
authors.forename: Mariano J
authors.initials: MJ
authors.lastname: Scian
authors.forename: Kellie J
authors.initials: KJ
authors.lastname: Archer
authors.forename: Jihee L
authors.initials: JL
authors.lastname: Suh
authors.forename: Krystle G
authors.initials: KG
authors.lastname: David
authors.forename: Qing
authors.initials: Q
authors.lastname: Ren
authors.forename: Todd W B
authors.initials: TW
authors.lastname: Gehr
authors.forename: Anne L
authors.initials: AL
authors.lastname: King
authors.forename: Marc P
authors.initials: MP
authors.lastname: Posner
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Mueller
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Maluf
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D051799:Delayed Graft Function / Q000097:blood / Q000235:genetics*; D003710:Demography; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D003404:Creatinine