الفهرس 
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Abstract
Introduction: kidney transplantation is the best treatment for end stage kidney disease. The graft and patient outcomes depend on the use of immunosuppressive drugs. Acute allograft rejection is one of the most common post-transplant complications that mostly occurs in early post-operative months. However, it can occur at any time in the functioning graft. It can be classified into T cell mediated, antibody mediated and vascular rejection according to immunological and pathological mechanism. Over immunosuppression can lead to serious infections and under immunosuppression can lead to allograft rejection, so it was essential for nephrologists to individualize immunosuppression therapy. Tacrolimus is the backbone of immunosuppression that has narrow therapeutic window and great intra and inter individual variation in pharmacokinetics. Tacrolimus is a substrate for multidrug resistant 1 (MDR-1) gene that encodes for Permeation glycoprotein (P-gp). Permeation glycoprotein (P-gp) acts as a membrane efflux pump transporting several molecules through cell membranes. Although many non-genetic factors, including age, ethnicity, and organ function influence the effects of tacrolimus, the pharmaco-genetics and gene sequence variability may account for 20–95% of variability in drug disposition and effects among individuals and different races. Several single nucleotide polymorphisms (SNPs) have been reported in the MDR1 gene which can affect the metabolism of drugs, the pharmacological action and toxicity profile of a vast number of therapeutic agents The aim of work: we aimed to evaluate the effect of 2 SNPs of MDR1 gene: C3435T (rs1045642) and G2677T (rs2032582) on the risk of acute rejection and on tacrolimus trough levels in Egyptian pediatric kidney transplant recipients. Research Plan: We conducted a retrospective case control study including 83 kidney transplant recipients following at kidney transplant clinic at Abo El Reesh hospital in the period between 2019 and 2021 and who weremaintained on tacrolimus immunosuppression. We included 80 age and gender matched healthy controls after exclusion of any renal disease or family history of renal failure among them. Results: The present study concluded that in MDR1 (C3435T), CC, CT genotypes and C allele were significantly associated with risk of AR when compared to none AR (P=0.008, 0.001 and 0.01 respectively). This means that the presence of single C allele of C3435T SNP may be a risk factor for AR. The required TAC doses to achieve the target trough level were significantly higher among CC than CT than TT genotypes through the 1st 6 months after KT. While, in MDR1 (G2677T), GT, TT genotypes and T allele were associated with AR when compared to none AR (P=0.023, 0.033 and 0.028 respectively). This means that the presence of single T allele in G2677T SNP may be a risk factor for AR. The required TAC doses to achieve trough level were significantly higher among TT than GT than GG genotypes through the 1st 6 months after KT. Conclusion: MDR1 gene polymorphism may be a risk factor for AR and this can be attributed to its effect on TAC pharmacokinetics. Tacrolimus therapy may be tailored according to the recipient genotype for better graft and patients’ outcomes. Recommendations: Further multicenter and large sample size studies may be required to provide clear evidence of usefulness of MDR 1 SNP as a clinical tool for personalizing IS therapy.