Adrien Flahault1, Dany Anglicheau2,3, Marie-Anne Loriot2,4, Eric Thervet2,5, Nicolas Pallet2,4. 1. College de France, Laboratory of Central Neuropeptides in the Regulation of Body Fluid Homeostasis & Cardiovascular Functions, CIRB, INSERM U1050, Paris, France. 2. Paris Descartes University, Sorbonne Paris Cité, INSERM UMRS 1147, Paris, France. 3. Department of Nephrology & Kidney Transplantation, Necker Hospital, Assistance Publique Hôpitaux de Paris, Paris, France. 4. Clinical Chemistry Department, Hôpital Européen Georges Pompidou Assistance Publique Hôpitaux de Paris, Paris, France. 5. Department of Nephrology, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, Paris, France.
Abstract
AIM: Meta-analyses and large cohort studies provide confusing results on the association of the CYP3A5 6986A>G allelic variant and adverse outcomes in kidney transplant recipients under tacrolimus-based immunosuppressive regimen. A residual effect of CYP3A5 recipient genotype is unexpected if kidney transplant recipients have similar exposure of tacrolimus. PATIENTS & METHODS: We have undertaken a population-based, observational study, to investigate all the consecutive patients who received a kidney transplant at the Necker hospital between 2005 and 2015, who were treated with tacrolimus and for whom the CYP3A5 genotype was available. RESULTS & CONCLUSION: We analyzed 577 patients followed for up to 5 years. We found a significant association of CYP3A5 genotypes with tacrolimus daily dose as well as with tacrolimus dose-adjusted concentrations. We however found no association of CYP3A5 genotypes with histology scores on biopsies, measured renal function, biopsy-proven acute rejection episodes and graft survival.
AIM: Meta-analyses and large cohort studies provide confusing results on the association of the CYP3A5 6986A>G allelic variant and adverse outcomes in kidney transplant recipients under tacrolimus-based immunosuppressive regimen. A residual effect of CYP3A5 recipient genotype is unexpected if kidney transplant recipients have similar exposure of tacrolimus. PATIENTS & METHODS: We have undertaken a population-based, observational study, to investigate all the consecutive patients who received a kidney transplant at the Necker hospital between 2005 and 2015, who were treated with tacrolimus and for whom the CYP3A5 genotype was available. RESULTS & CONCLUSION: We analyzed 577 patients followed for up to 5 years. We found a significant association of CYP3A5 genotypes with tacrolimus daily dose as well as with tacrolimus dose-adjusted concentrations. We however found no association of CYP3A5 genotypes with histology scores on biopsies, measured renal function, biopsy-proven acute rejection episodes and graft survival.
Authors: Karola Warzyszyńska; Michał Zawistowski; Edyta Karpeta; Agnieszka Jałbrzykowska; Maciej Kosieradzki Journal: Ann Transplant Date: 2022-07-26 Impact factor: 1.479