Wcn26-2486 the Dilemma of Induction Immunosuppression in Low Immunological Risk Kidney Transplant Recipients- A Prospective Randomised Study From Eastern India Comparing Basiliximab Versus No Induction Immunosuppression

Introduction: Tacrolimus is the drug of choice immunosuppressant in renal transplant (RTx) recipients, but due to its narrow therapeutic index, wider inter and intra patient variability and difficult pharmacogenomics, optimized dose of tacrolimus is difficult to achieve.The study is focused to investigate the cytochrome P450 3A5 (CYP3A5) and ATP-Binding Casette transporter B1 (ABCB1) polymorphisms among RTx recipients in association with daily tacrolimus dose requirements, tacrolimus blood trough levels and clinical outcomes in terms of rejection, co-infections and side effects.Methods: This retrospective cross-sectional study is conducted at Renal transplant Unit of Dow University Hospital, DUHS.A total of 83 subjects who have received renal transplant and on tacrolimus for more than one year have been recruited for genotyping analysis (via primer specific PCR, Gel electrophoresis and RFLP enzymes) of CYP3A5 and ABCB1 polymorphisms in association with pharmacokinetic details of tacrolimus and relevant clinical outcomes.Results: In this study, 79.8% (n = 64) were males, the mean age of transplant recipients were 37 years while median duration since transplantation was 28 months.15.6% (n = 10) were pre-emptive transplant while hypertensive nephropathy (42.35%, n = 27) was found to be the most common cause of ESRD in our study.Post transplant Diabetes Mellitus was common in 57.83% (n = 48) of subjects.The mean daily dose of tacrolimus was 2.5 0.5mg, oral predinisolone (15mg) and mycophenolate mofetil (1000mg).The mean tacrolimus blood trough levels were 7.6 3.7 mg/dl, 7.1 2.1 mg/dl and 5.9 3.9 mg/dl at 0, 3 and 6 months, retrospectively.All subjects were tested CYP3A5*1/3 (non-expressors) genotype while homozygous mutants ABCB1 rs1045642 and rs2032582 have considerably higher blood trough concentration levels as compared to heterozygous or homozygous wild type (9.3 1.1 mg/dl versus 6.3 3.2 mg/dl).Significant association of higher neutrophils/ platelets ratio (p # 0.001), higher CRP levels (p # 0.045), frequent infections and hospitalization (p # 0.001) was reported in homozygous mutants ABCB1 rs2032582 while CYP3A5*1/3 non expressors has significantly increased fasting blood sugar levels, hypertriglyceridemia and hyperuricemia.Conclusion: Our results support the hypothesis that CYP3A5 and ABCB1 polymorphisms have major influence in achieving targeted tacrolimus blood trough levels and polymorphisms may lead to abnormally higher rate of adverse effects which may affect long term graft functions.It is highly recommended that timely detection of theses notable polymorphisms may reduce the titration time in tacrolimus dose optimization thus reducing side effects and improving the outcomes.