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Human Pregnane X Receptor Genotype of the Donor but Not of the Recipient Is a Risk Factor for Delayed Graft Function After Renal Transplantation
Author(s) -
Hauser I A,
Kruck S,
Gauer S,
Nies A T,
Winter S,
Bedke J,
Geiger H,
Hoefeld H,
Kleemann J,
AsbeVollkopf A,
Engel J,
Burk O,
Schwab M,
Schaeffeler E
Publication year - 2012
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2011.346
Subject(s) - pregnane x receptor , transplantation , genotype , renal function , medicine , logistic regression , univariate analysis , immunosuppression , kidney transplantation , kidney , pharmacology , endocrinology , urology , oncology , transcription factor , biology , nuclear receptor , multivariate analysis , genetics , gene
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. Clinical Pharmacology & Therapeutics (2012); 91 5, 905–916. doi: 10.1038/clpt.2011.346