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 language | English |
|---|---|
| Pages (from-to) | 988-995 |
| Number of pages | 8 |
| Journal | Journal of Surgical Research |
| Volume | 178 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Dec 2012 |
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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 journal › Article
}
TY - JOUR
T1 - Donor age and ABCB1 1199G>A genetic polymorphism are independent factors affecting long-term renal function after kidney transplantation
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
PY - 2012/12
Y1 - 2012/12
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.
KW - Donor
KW - Genetic polymorphisms
KW - Kidney transplantation
KW - Renal function
UR - http://www.scopus.com/inward/record.url?scp=84869082325&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84869082325&partnerID=8YFLogxK
U2 - 10.1016/j.jss.2012.06.070
DO - 10.1016/j.jss.2012.06.070
M3 - Article
C2 - 22835948
AN - SCOPUS:84869082325
VL - 178
SP - 988
EP - 995
JO - Journal of Surgical Research
JF - Journal of Surgical Research
SN - 0022-4804
IS - 2
ER -