Choong Chiau Ling, Islahudin Farida, Wong Hin-Seng, Yahya Rosnawati, Mohd Tahir Nor Asyikin, Makmor-Bakry Mohd
Center of Quality Medicine Management, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia.
Department of Nephrology, Selayang Hospital, Ministry of Health Malaysia, Batu Caves 68100, Malaysia.
J Pers Med. 2024 Apr 22;14(4):440. doi: 10.3390/jpm14040440.
Personalized medicine in kidney transplantation has the potential to improve outcomes and reduce complications. The aim of this study was to investigate the influence of single nucleotide polymorphisms in genes encoding metabolizing enzymes (CYP3A5) and transporters (ABCC2) on clinical outcomes (acute graft failure and/or acute tubular necrosis (ATN)) in kidney transplant recipients (KTR). This was a multicenter, retrospective cohort study where adult KTR who had undergone kidney transplantation between 2020 and 2021 and received tacrolimus-mycophenolate treatment were enrolled in the study. DNA was extracted from collected blood samples using a commercially available kit. , and SNP were determined by polymerase chain reaction. Of the total 39 patients included, nine (23.1%) KTR had an incidence of acute graft failure and/or ATN. A multiple logistic regression showed wildtype allele had a higher risk of developing acute graft rejection and/or ATN compared to the variant allele carriers (adjusted Odd Ratios [aOR]: 27.675, = 0.038). Recipients who had delayed graft function (aOR: 49.214, = 0.012) and a history of CMV infection (aOR: 18.097, = 0.009) were at 49.2 and 18.1-times increased risk for acute graft failure and/or ATN, respectively. The large aOR was inevitable due to the small sample size and required cautious interpretation. This is the first study to determine the effect of the genetic polymorphism on clinical outcomes in Malaysian KTR and forms the basis for further work on effects in long-term KTR.
肾移植中的个性化医疗有改善治疗效果并减少并发症的潜力。本研究的目的是调查编码代谢酶(CYP3A5)和转运蛋白(ABCC2)的基因中的单核苷酸多态性对肾移植受者(KTR)临床结局(急性移植失败和/或急性肾小管坏死(ATN))的影响。这是一项多中心回顾性队列研究,纳入了2020年至2021年间接受肾移植并接受他克莫司-霉酚酸治疗的成年KTR。使用市售试剂盒从采集的血样中提取DNA。通过聚合酶链反应确定 、 和 SNP。在总共纳入的39例患者中,9例(23.1%)KTR发生了急性移植失败和/或ATN。多元逻辑回归显示,与变异等位基因携带者相比,野生型 等位基因发生急性移植排斥和/或ATN的风险更高(调整后的比值比[aOR]:27.675, = 0.038)。移植功能延迟的受者(aOR:49.214, = 0.012)和有巨细胞病毒感染史的受者(aOR:18.097, = 0.009)发生急性移植失败和/或ATN的风险分别增加49.2倍和18.1倍。由于样本量小,较大的aOR是不可避免的,需要谨慎解释。这是第一项确定 基因多态性对马来西亚KTR临床结局影响的研究,并为进一步研究其对长期KTR的影响奠定了基础。