title: Human pregnane X receptor genotype of the donor but not of the recipient is a risk factor for delayed graft function after renal transplantation.
abstract: Delayed graft function (DGF) is an important complication in renal transplantation, contributing significantly to decrease in long-term allograft survival. In addition to donor- and recipient-related risk factors such as immunosuppression, altered renal excretion of xenobiotics by membrane transporters may influence DGF. Using DNA samples from recipients and donors, we assessed the impact on DGF of genetic variants in P-glycoprotein (ABCB1), multidrug resistance protein 2 (ABCC2), and the nuclear pregnane X receptor (PXR/NR1I2), which regulates the transcription of enzymes and transporters. In our local cohort of renal transplant recipients (n = 178), DGF occurred in 27.5%. The PXR 8055TT genotype of the donor only (not of the recipient) was significantly associated with an increased risk for DGF. This finding emerged from univariate as well as multivariate logistic regression analysis including 16 nongenetic factors and held true after correction for multiple testing. Our findings provide the first evidence that PXR may be associated with risk of DGF, independent of previously identified risk factors.
authors.affiliation: Department of Nephrology, Medical Clinic II, University Hospital Johann Wolfgang Goethe-University, Frankfurt am Main, Germany. i.hauser@em.uni-frankfurt.de
authors.forename: I A
authors.initials: IA
authors.lastname: Hauser
authors.forename: S
authors.initials: S
authors.lastname: Kruck
authors.forename: S
authors.initials: S
authors.lastname: Gauer
authors.forename: A T
authors.initials: AT
authors.lastname: Nies
authors.forename: S
authors.initials: S
authors.lastname: Winter
authors.forename: J
authors.initials: J
authors.lastname: Bedke
authors.forename: H
authors.initials: H
authors.lastname: Geiger
authors.forename: H
authors.initials: H
authors.lastname: Hoefeld
authors.forename: J
authors.initials: J
authors.lastname: Kleemann
authors.forename: A
authors.initials: A
authors.lastname: Asbe-Vollkopf
authors.forename: J
authors.initials: J
authors.lastname: Engel
authors.forename: O
authors.initials: O
authors.lastname: Burk
authors.forename: M
authors.initials: M
authors.lastname: Schwab
authors.forename: E
authors.initials: E
authors.lastname: Schaeffeler
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D051799:Delayed Graft Function / Q000209:etiology*; D005260:Female; D005838:Genotype; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D015999:Multivariate Analysis; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000235:genetics*; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000089762:Multidrug Resistance-Associated Protein 2; C000625852:NR1I2 protein, human; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid