There are 3 clinical trials
The purpose of this study is to determine whether functional genetic variants can affect tacrolimus dose corrected trough levels and associate with the side effects in Chinese renal transplantation and liver transplantation.
Full understanding of this mechanism is important for the personalized use of tacrolimus and reducing the risk of side effects.The CYP3A5*3 (A6986G) resulting in a splicing defect and the absence of protein activity, was identified as a functional variant (Kuehl P.2001). --- A6986G ---
Description: time to acute rejection
Measure: Kidney transplant recipient genotypes Time: Day 0 to Day 30Description: time to Calcineurin Inhibitor (CNI)-related nephrotoxicities
Measure: Kidney transplant recipient genotypes Time: Day 0 to Day 30Description: time to Calcineurin Inhibitor (CNI)-related neurotoxicities
Measure: Kidney transplant recipient genotypes Time: Day 0 to Day 30Description: time to acute rejection
Measure: Liver transplant recipient genotypes Time: Day 0 to Day 30Description: time to Calcineurin Inhibitor (CNI)-related nephrotoxicities
Measure: Liver transplant recipient genotypes Time: Day 0 to Day 30Description: time to Calcineurin Inhibitor (CNI)-related neurotoxicities
Measure: Liver transplant recipient genotypes Time: Day 0 to Day 30Description: time to acute rejection
Measure: Liver donor genotypes Time: Day 0 to Day 30Description: time to Calcineurin Inhibitor (CNI)-related nephrotoxicities
Measure: Liver donor genotypes Time: Day 0 to Day 30Description: time to Calcineurin Inhibitor (CNI)-related neurotoxicities
Measure: Liver donor genotypes Time: Day 0 to Day 30The purpose is to define if calcineurin activity is a better biological parameter than blood concentration for the therapeutic tacrolimus monitoring.
Genotyping of CYP3A5 * 3 (A6986G) and mdr-1: mutations of these proteins could explain the changes of absorption of tacrolimus. --- A6986G ---
Description: Genotyping of CYP3A5 * 3 (A6986G) and mdr-1: mutations of these proteins could explain the changes of absorption of tacrolimus. For each patient, during the first month of treatment, 5 ml of blood will be collected on EDTA tube. Genotyping is realized by the allelic discrimination technique Taqman, on a ABI Prism 7000 (TaqMan ®) in the Molecular Biology unit, Pharmacogenetics and Hormonology Bicêtre Hospital
Measure: Pharmacogenetics (3A5) Time: at day 8, day 15, day 21, day 28, month 2 and month 3Kidney transplantation is the most appropriated treatment in end stage renal failure patients in order to improve quality of life. However, patients have to take immunosuppressive drugs to prevent graft rejection. Tacrolimus is the most common immunosuppressive drug used now. However, tacrolimus has narrow therapeutic level and needs regularly therapeutic monitor because of inter-individual variation in dosage regimen. Not only age, body weight and drug interaction but also genetic factor in metabolic pathway of tacrolimus plays an important role in tacrolimus blood level. Previous data showed CYP3A5 genetic polymorphism was significant effect tacrolimus blood level. From previous study showed the mean dose of tacrolimus required for the induction phase was significantly higher (P= 0.006) in the CYP3A5*1/*1 group at 0.142±0.050 mg/kg/day than that required by patients who carried either the CYP3A5*1/*3 group of 0.097±0.040 mg/kg/day or the CYP3A5*3/*3 group of 0.077±0.020 mg/kg/day. Tacrolimus maintenance dose required for CYP3A5*1/*1 group of 0.12±0.03 mg/kg/day was 1.3 times higher (P<0.0001) than used for the CYP3A5*1/*3 at 0.09±0.03 mg/kg/day and 2.4 times higher than the CYP3A5*3/*3 group of 0.05±0.02 mg/kg/day. Therefore, the investigators plan to investigate a prospective study to determine the clinical outcome of tacrolimus treatment in kidney transplant recipients between genotype guided dosage regimen group and conventional group.
CYP3A5*3, an A to G transition (A6986G) within intron 3 results in the production of a truncated protein, is the most common allele variant. --- A6986G ---
Description: Proportion of patients whose tacrolimus level were in therapeutic range at day 3 post transplantation
Measure: Mean tacrolimus level Time: at day 3 after transplantationDescription: Proportion of patients whose tacrolimus level were in therapeutic range at day 1, 3, 5, 7, 14, 30,60, 90, 120, 150 and 180 days post transplantation
Measure: Mean tacrolimus level Time: at day 1, 3, 5, 7, 14, 30,60, 90, 120, 150 and 180 days post transplantationDescription: Compare incidence of delay graft rejection between 2 groups
Measure: Incidence of delay graft rejection Time: day 1- 6 month after transplantationDescription: Compare mean GFR level at day 7, 14, 30, 60, 90, 120, 150, and 180 days after transplantation
Measure: Mean GFR level Time: at day 7, 14, 30, 60, 90, 120, 150, and 180 days after transplantation