Donor age and ABCB1 1199G>A genetic polymorphism are independent factors affecting long-term renal function after kidney transplantation

Martine De Meyer, Vincent Haufroid, Laure Elens, Fabio Fusaro, Damiano Patrono, Luc De Pauw, Nada Kanaan, Eric Goffin, Michel Mourad

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: In renal tubular cells, cytochrome P4503A enzyme and adenosine triphosphate-binding cassette transporter activities result in intracellular drug or metabolite exposure variability, depending on genetic polymorphisms. Our aim was to establish whether long-term renal function is affected by genetic polymorphisms in biotransformation enzymes and drug transporters of the donor after kidney transplantation. Materials and methods: The study was conducted in a selected cohort of 97 kidney recipients. Genotyping of donors was performed on renal biopsy samples obtained before transplantation. Serum creatinine levels and Cockcroft-Gault estimated glomerular filtration rate were considered 1 y after transplantation and at the last follow-up. Results: Long-term function was significantly better in recipients of an organ from donors carrying the ABCB1 1199A mutated allele (median and range creatinine values were 1.1 mg/dL [0.8-1.5mg/dL] in case of at least one ABCB1 1199A allele versus 1.5 mg/dL [0.7-3.7 mg/dL] for homozygous carriers of wild-type allele, P <0.01). ABCB1 1199G>A polymorphism and donor age had an independent impact on both serum creatinine and estimated glomerular filtration rate. Unlike donor age, the mutated ABCB1 1199A allele was found to have a protective effect on renal function. Conclusions: Donor age and ABCB1 1199G>A polymorphism affect long-term renal function after transplantation. Analysis of genetic factors offers a promising approach to calcineurin inhibitor toxicity risk assessment.

Original languageEnglish
Pages (from-to)988-995
Number of pages8
JournalJournal of Surgical Research
Volume178
Issue number2
DOIs
Publication statusPublished - Dec 2012

Fingerprint

Genetic Polymorphisms
Kidney Transplantation
Tissue Donors
Kidney
Alleles
Creatinine
Transplantation
Glomerular Filtration Rate
Enzymes
Cytochromes
Biotransformation
Serum
Pharmaceutical Preparations
Statistical Factor Analysis
Adenosine Triphosphate
Biopsy

Keywords

  • Donor
  • Genetic polymorphisms
  • Kidney transplantation
  • Renal function

ASJC Scopus subject areas

  • Surgery

Cite this

Donor age and ABCB1 1199G>A genetic polymorphism are independent factors affecting long-term renal function after kidney transplantation. / De Meyer, Martine; Haufroid, Vincent; Elens, Laure; Fusaro, Fabio; Patrono, Damiano; De Pauw, Luc; Kanaan, Nada; Goffin, Eric; Mourad, Michel.

In: Journal of Surgical Research, Vol. 178, No. 2, 12.2012, p. 988-995.

Research output: Contribution to journalArticle

De Meyer, Martine ; Haufroid, Vincent ; Elens, Laure ; Fusaro, Fabio ; Patrono, Damiano ; De Pauw, Luc ; Kanaan, Nada ; Goffin, Eric ; Mourad, Michel. / Donor age and ABCB1 1199G>A genetic polymorphism are independent factors affecting long-term renal function after kidney transplantation. In: Journal of Surgical Research. 2012 ; Vol. 178, No. 2. pp. 988-995.
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AU - De Meyer, Martine

AU - Haufroid, Vincent

AU - Elens, Laure

AU - Fusaro, Fabio

AU - Patrono, Damiano

AU - De Pauw, Luc

AU - Kanaan, Nada

AU - Goffin, Eric

AU - Mourad, Michel

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N2 - Background: In renal tubular cells, cytochrome P4503A enzyme and adenosine triphosphate-binding cassette transporter activities result in intracellular drug or metabolite exposure variability, depending on genetic polymorphisms. Our aim was to establish whether long-term renal function is affected by genetic polymorphisms in biotransformation enzymes and drug transporters of the donor after kidney transplantation. Materials and methods: The study was conducted in a selected cohort of 97 kidney recipients. Genotyping of donors was performed on renal biopsy samples obtained before transplantation. Serum creatinine levels and Cockcroft-Gault estimated glomerular filtration rate were considered 1 y after transplantation and at the last follow-up. Results: Long-term function was significantly better in recipients of an organ from donors carrying the ABCB1 1199A mutated allele (median and range creatinine values were 1.1 mg/dL [0.8-1.5mg/dL] in case of at least one ABCB1 1199A allele versus 1.5 mg/dL [0.7-3.7 mg/dL] for homozygous carriers of wild-type allele, P <0.01). ABCB1 1199G>A polymorphism and donor age had an independent impact on both serum creatinine and estimated glomerular filtration rate. Unlike donor age, the mutated ABCB1 1199A allele was found to have a protective effect on renal function. Conclusions: Donor age and ABCB1 1199G>A polymorphism affect long-term renal function after transplantation. Analysis of genetic factors offers a promising approach to calcineurin inhibitor toxicity risk assessment.

AB - Background: In renal tubular cells, cytochrome P4503A enzyme and adenosine triphosphate-binding cassette transporter activities result in intracellular drug or metabolite exposure variability, depending on genetic polymorphisms. Our aim was to establish whether long-term renal function is affected by genetic polymorphisms in biotransformation enzymes and drug transporters of the donor after kidney transplantation. Materials and methods: The study was conducted in a selected cohort of 97 kidney recipients. Genotyping of donors was performed on renal biopsy samples obtained before transplantation. Serum creatinine levels and Cockcroft-Gault estimated glomerular filtration rate were considered 1 y after transplantation and at the last follow-up. Results: Long-term function was significantly better in recipients of an organ from donors carrying the ABCB1 1199A mutated allele (median and range creatinine values were 1.1 mg/dL [0.8-1.5mg/dL] in case of at least one ABCB1 1199A allele versus 1.5 mg/dL [0.7-3.7 mg/dL] for homozygous carriers of wild-type allele, P <0.01). ABCB1 1199G>A polymorphism and donor age had an independent impact on both serum creatinine and estimated glomerular filtration rate. Unlike donor age, the mutated ABCB1 1199A allele was found to have a protective effect on renal function. Conclusions: Donor age and ABCB1 1199G>A polymorphism affect long-term renal function after transplantation. Analysis of genetic factors offers a promising approach to calcineurin inhibitor toxicity risk assessment.

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