Urological and Genital Diseases: Renal transplantation Urological and Genital Diseases Renal transplantation
Conditions
Interventions
Patients identified as being genetic expressors of CYP3A5 (at least one CYP3A5*1 allele in the absence of CYP3A5*6 or 7*) will be randomised to initial tacrolimus dosing on their CYP3A5 genotype or to
Sponsors
Record Provided by the NHSTCT Register - 2007 Update - Department of Health (UK)
Eligibility
Inclusion criteria
Inclusion criteria: All non-black (genetically from Sub-Saharan Africa) patients on the transplant waiting list for St George's Hospital will be invited to participate. We already give black patients an increased starting dose of tacrolimus as standard practice. At present there are 170 patients on the waiting list and we would anticipate performing 80-100 renal transplant operations annually. All subjects will be given written informed consent. Individuals will be genotyped for SNPs using DNA prepared from peripheral blood leucocytes. We will type for CYP3A5*1/*3, CYP3A%*6 and CYP3A5*7. CYP3A5*6 and CYP3A5*7 are present in <10% of the population and may coexist with CYP3A5*1 resulting in non-expression of CYP3A5. We will determine the genotype of the SNPs in exons 12,21 and 26 of MDR-1 to define the haplotypeas has been recently suggested to be a more satisfactory approach than looking at single polymorphisms. We have established methods based on reverse transcriptase polymerase chain reaction (PCR) followed by use of restriction fragment length polymorphisms (RFLP) for MDR-1 genotyping. CYP3A5 genotyping will be performed using a LightCycler™.
Exclusion criteria
Exclusion criteria: Not provided at time of registration
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of patients achieving target blood tacrolimus concentrations, tacrolimus measurements within the target range of 15-20 ng/ml during the first 7 days after transplantation and 10-15 ng/ml during the following 7 days. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The incidence of all episodes of rejection including episodes treated as rejection without biopsy confirmation 2. The serum creatinine concentration at one year after transplantation with glomerular filtration rate calculated using the MDRD formula 3. The incidence of calcineurin inhibitor toxicity | — |
Countries
United Kingdom
Outcome results
None listed