Date: Monday, June 3, 2019
Session Time: 4:30pm-6:00pm
Presentation Time: 5:06pm-5:18pm
Location: Room 210
*Purpose: This study was to develop a clinical pharmacogenetic model to predict the efficacy of sirolimus during the early administration in renal transplant recipients. 70 recipients were enrolled according to the inclusion and exclusion criteria.
*Methods: Blood samples were collected and total DNA was extracted. Target sequencing based on next-generation sequencing was used to detect all single nucleotide polymorphisms (SNPs) in 9 genes related to the sirolimus metabolism in vivo (CYP3A4, CYP3A5, CYP2C8, CYP2C19, ABCB1, POR, PPARA, UGT1A8, UGT1A9, UGT2B7). Medical records related to the sirolimus metabolism were also collected. Logistic regression analysis adjusted by the confounding factors was conducted to identify the potential associations of all detected SNPs with the sirolimus concentrations on 7 days and 1 month after the administration of sirolimus within the first 3 months after kidney transplantation. A clinical score was designed by simplifying regression coefficients of the independent variables. Cutoff levels were chosen based on the clinical score, and positive and negative response rates were calculated. An evaluation of the model was performed in a second group of recipients containing 100 recipients.
*Results: The model for sirolimus efficacy consisted of gender, body mass index, immunosuppressive protocols, the incidence of delayed graft function and acute rejection, as well as 5 SNPs in the CYP3A4, CYP3A5, ABCB1 and UGT1A8 genes. This prediction model was transformed into a scoring system ranging from 0 to 11.5. Scores of ≤3.5 had a true positive response rate of 95%, while scores of ≥8 categorized as either responders or non-responders, whereas 18.6% of the patients were categorized using a non-genetic model. Evaluations of the model in second group supported the results.
*Conclusions: In conclusion, our study established a clinical pharmacogenetics model to predict the efficacy of sirolimus administration in recipients during early phase following renal transplantation. This model may lead to the better-tailored initial treatment decision of sirolimus within the first 3 months in renal transplant recipients.
To cite this abstract in AMA style:Wang Z, Fei S, Han Z, Tao J, Tan R, Gu M. A Clinical Pharmacogenetic Model to Predict the Efficacy of Sirolimus during the Early Administration in Renal Transplant Recipients [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/a-clinical-pharmacogenetic-model-to-predict-the-efficacy-of-sirolimus-during-the-early-administration-in-renal-transplant-recipients/. Accessed July 7, 2020.
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