Analysis of the Effect of Donor CYP3A5 Gene Polymorphism on Early Tacrolimus Concentration and Postoperative Acute Renal Injury After Liver Transplantation

Analysis of the Effect of Donor CYP3A5 Gene Polymorphism on Early Tacrolimus Concentration and Postoperative Acute Renal Injury After Liver Transplantation

Tacrolimus is the most commonly used immunosuppressant for preventing and treating rejection after liver transplantation. However, its treatment window is narrow, the pharmacokinetic individual differences are large, routine dose according to body weight, sometimes low dose will cause graft rejection of patients, or high dose will lead to infection and liver and kidney toxicity and other adverse reactions. Moreover, the conventional drug testing can not fully reflect the efficacy of tacrolimus, and there are shortcomings of lag, experience and passivity. FK506 is metabolized primarily by cytochrome P450 member 3A5 in the liver and intestines. CYP3A5*3 is the most important factor determining the expression level of CYP3A5. This mutation can cause variable shear and produce unstable protein, so that patients carrying CYP3A5*3/*3 gene do not express CYP3A5. Acute kidney injury is a common and important complication after liver transplantation. Despite recent advances in organ preservation, surgical techniques, and immunosuppressive protocols, the incidence of AKI after orthotopic liver transplantation remains high. AKI has a significant impact on both short - and long-term prognosis of orthotopic liver transplantation recipients. Studies have shown that orthotopic liver transplantation recipients with AKI have significantly higher mortality rates in hospital, at 28 days and at 1 year after surgery than those without AKI. In this study, the relationship between donor and recipient CYP3A5 gene polymorphism and tacrolimus concentration was investigated, and the effect of donor and recipient CYP3A5 gene polymorphism and tacrolimus concentration on acute kidney injury after liver transplantation was investigated. To provide guidance for individual administration of gene-directed tacrolimus in patients, and provide basis for prevention and reduction of postoperative acute kidney injury in liver transplantation patients.

Inclusion Criteria:

1. Patients undergoing orthotopic liver transplantation in our center.
2. The postoperative immunosuppression regimen was tacrolimus、methylprednisolone and balipremumab for injection in all cases,and no drugs that interacted with tacrolimus were used.
3. The postoperative follow-up time was greater than 6 months and no serious rejection occurred during the follow-up period.

Exclusion Criteria:

1. Combined organ transplantation.
2. liver transplant patients on other immunosuppressive regimens.
3. Preoperative CKD or need RRT.
4. Preoperative serum creatinine (SCr) > 133 mol/L.
5. Loss of follow-ups.