A prospective observational study on the difference in blood AUC (Area under concentration–time curve) levels of tacrolimus between non-expressers and expressers of CYP3A5 gene polymorphism and its effect on graft outcomes in renal allograft recipients

To study the effects of genetic variation and blood levels of the drug tacrolimus and transplant kidney function in kidney transplant recipient patients in tertiary care hospital. Tacrolimus is an important drug used for suppressing immunity and preventing kidney graft loss. But Tacrolimus drug level in blood should be maintained within a narrow range from 4-11 ng/ml post renal transplant. Tacrolimus is eliminated from the body by the effect of the CYP3A5 gene. Patients in general can have varied gene pattern. If the patient has no genetic variation (non-Expressers), the tacrolimus level will be higher than the recommended range and will lead to toxicity. If the patient has genetic variation (Expressers), tacrolimus level is low than this range it will lead to graft rejection. Thus, it is important to find out the variation in genetics and to study the effects of genetic variation and how it affects tacrolimus blood levels which are necessary for the maintenance of the graft to function properly. This could potentially save graft function and survival.

 This study basically aims to determine if by finding out the genetic variation which affects tacrolimus blood levels, we can give tacrolimus dosage accordingly so that it will be beneficial to avoid either graft loss on one hand if levels are low and tacrolimus toxicity if blood level and exposure is high on another hand. All patients enrolled in the study will be given tacrolimus 0.13mg/kg to look at therapeutic blood levels and to assess for kidney graft function in the form of rejection and drug toxicity. Also, we will find out how frequent is genetic variation among our population in CMC and its effect on graft survival.