BACKGROUND Kidney transplantation is an effective renal replacement therapy for improving survival and quality of life in chronic kidney disease patients.Kidney transplant recipients need lifelong immunosuppression to...BACKGROUND Kidney transplantation is an effective renal replacement therapy for improving survival and quality of life in chronic kidney disease patients.Kidney transplant recipients need lifelong immunosuppression to prevent rejection and allograft dysfunction.Tacrolimus,a calcineurin inhibitor,is metabolized differently based on cytochrome P4503A(CYP3A)5 genetic variations and this impacts the graft outcome.AIM To examine the clinical outcomes in kidney transplant recipients affected by the variable metabolism of tacrolimus due to the CYP3A5 genetic variation,emphasizing personalized immunosuppression strategies to optimize efficacy,minimize toxicity,and enhance long-term graft survival.METHODS A retrospective study was conducted at a tertiary care center in Central India on 95 kidney transplant recipients.Patient demographics,medical history,CYP3A5 polymorphism,post-transplant investigations,graft biopsy results,preexisting comorbidities,history of post–kidney transplant infections,and new onset diabetes after transplantation(NODAT)was collected.Tacrolimus was initiated at 0.1 mg/kg/day for CYP3A5 expressors and 0.05 mg/kg/day for non-expressors,with dose adjustments to maintain target C0 levels of 7-10 ng/mL for first 6 months and 5-7 ng/mL from 6 months to 12 months posttransplant.Patients were followed regularly for one year for glomerular filtration rate(GFR),creatinine,and the tacrolimus trough concentration(ng/mL)/daily tacrolimus dose(mg/kg/day)ratio(C/D).A P value≤0.05 was considered statistically significant.RESULTS Kidney transplant recipients were classified as expressors(CYP3A51 carriers,n=35)and non-expressors(CYP3A5*3*3,n=60).Both groups were comparable for age,sex,and donor characteristics.Tacrolimus dose was comparable post-transplant except at 6 months and 12 months,where expressors required higher doses.Kidney function(creatinine and estimated GFR),NODAT,hypomagnesemia,and infections showed no significant differences between the two groups over 12 months of follow-up.Biopsy-proven acute rejection(BPAR)was found to be more in expressors(22.9%vs 13.3%,P=0.2340)though it was not found to be statistically significant.Nonexpressors had a significantly higher tacrolimus levels and C/D ratio at multiple follow-ups.CONCLUSION CYP3A5 expressors require higher tacrolimus doses to maintain therapeutic levels as compared to non-expressors.BPAR was higher in expressors but the difference was not significant.Graft function,infection rate,and NODAT were comparable irrespective of CYP3A5 expression status,emphasizing the importance of pretransplant CYP3A5 genotyping and therapeutic drug monitoring to guide tacrolimus dosing for individualized immunosuppressive management.展开更多
目的:急性脑梗死病情进展迅速,常导致神经不可逆损伤,预后较差,需寻找相关预后标志物以了解预后情况。本研究旨在分析细胞色素P450(cytochrome P450,CYP)3A5基因多态性联合血清微RNA-543(microRNA-543,miR-543)预测急性脑梗死患者预后...目的:急性脑梗死病情进展迅速,常导致神经不可逆损伤,预后较差,需寻找相关预后标志物以了解预后情况。本研究旨在分析细胞色素P450(cytochrome P450,CYP)3A5基因多态性联合血清微RNA-543(microRNA-543,miR-543)预测急性脑梗死患者预后不良的价值。方法:选取2021年5月至2024年1月在郑州市第七人民医院诊断为急性脑梗死的176例患者作为研究对象,依据患者出院90 d后的门诊改良Rankin量表评分结果,将评分≤2的患者纳入预后良好组(n=92),评分>2的纳入预后不良组(n=84)。采用实时荧光定量PCR法检测治疗前血清miR-543水平,采用PCR法检测治疗前CYP3A5基因型,采用多因素Logistic回归分析影响急性脑梗死患者预后不良的因素,采用受试者操作特征(receiver operating characteristic,ROC)曲线分析CYP3A5基因rs776746位点GG基因型联合血清miR-543水平对急性脑梗死患者预后不良的预测价值。结果:CYP3A5基因rs776746位点上检出AA型、GA型、GG型3种基因型。预后不良组发病至溶栓时间长于预后良好组,血清miR-543水平、携带CYP3A5基因rs776746位点GG基因型及G等位基因、入院时美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分≥15和高血压患者比例均显著高于预后良好组(均P<0.001)。携带CYP3A5基因rs776746位点GG基因型和高miR-543水平是急性脑梗死患者预后不良的危险因素(均P<0.05)。CYP3A5基因rs776746位点GG基因型和血清miR-543水平单独及联合预测急性脑梗死患者预后不良的曲线下面积(area under the curve,AUC)分别为0.702、0.833、0.932,敏感度分别为52.38%、75.68%、92.86%,特异度分别为88.04%、78.33%、93.48%。结论:携带CYP3A5基因rs776746位点GG基因型和高miR-543水平均与急性脑梗死患者预后不良有关,二者联合可显著提高预测效能。展开更多
目的评价基于细胞色素P450(CYP)3A5*1基因多态性指导肝移植术后他克莫司(FK506)个体化用药的安全性和有效性。方法分析连续入组的100例首次行肝移植术受者的临床资料,并随机分为实验组和对照组,每组各50例。实验组术前对供、受者进行CYP...目的评价基于细胞色素P450(CYP)3A5*1基因多态性指导肝移植术后他克莫司(FK506)个体化用药的安全性和有效性。方法分析连续入组的100例首次行肝移植术受者的临床资料,并随机分为实验组和对照组,每组各50例。实验组术前对供、受者进行CYP3A5基因检测,并根据CYP3A5*1基因型确定FK506用药方案。观察术后7、14、28 d以及3、6、9、12个月两组受者FK506目标血药浓度达标率、肝功能恢复正常率以及随访过程中FK506调整用量次数。记录两组受者1年移植物存活率,及急性排斥反应、感染、急性肾损伤、消化道症状、新发高血压、新发糖尿病、感冒、皮疹等并发症的发生率。结果两组受者术后7、14 d FK506目标血药浓度达标率比较,差异均有统计学意义(均为P<0.05)。两组术后28 d及3、6、9、12个月FK506目标血药浓度达标率及术后7个观察时间点肝功能恢复正常率比较,差异均无统计学意义(均为P>0.05)。两组受者随访期间FK506剂量调整次数比较,差异有统计学意义(P=0.021)。两组受者术后及随访期间1年移植物存活率和并发症发生率比较,差异均无统计学意义(均为P>0.05)。结论根据CYP3A5*1基因多态性指导肝移植术后FK506个体化用药是安全的,能在术后早期提高受者FK506目标血药浓度达标率,并且可以有效减少随访期间药量调整次数。展开更多
文摘BACKGROUND Kidney transplantation is an effective renal replacement therapy for improving survival and quality of life in chronic kidney disease patients.Kidney transplant recipients need lifelong immunosuppression to prevent rejection and allograft dysfunction.Tacrolimus,a calcineurin inhibitor,is metabolized differently based on cytochrome P4503A(CYP3A)5 genetic variations and this impacts the graft outcome.AIM To examine the clinical outcomes in kidney transplant recipients affected by the variable metabolism of tacrolimus due to the CYP3A5 genetic variation,emphasizing personalized immunosuppression strategies to optimize efficacy,minimize toxicity,and enhance long-term graft survival.METHODS A retrospective study was conducted at a tertiary care center in Central India on 95 kidney transplant recipients.Patient demographics,medical history,CYP3A5 polymorphism,post-transplant investigations,graft biopsy results,preexisting comorbidities,history of post–kidney transplant infections,and new onset diabetes after transplantation(NODAT)was collected.Tacrolimus was initiated at 0.1 mg/kg/day for CYP3A5 expressors and 0.05 mg/kg/day for non-expressors,with dose adjustments to maintain target C0 levels of 7-10 ng/mL for first 6 months and 5-7 ng/mL from 6 months to 12 months posttransplant.Patients were followed regularly for one year for glomerular filtration rate(GFR),creatinine,and the tacrolimus trough concentration(ng/mL)/daily tacrolimus dose(mg/kg/day)ratio(C/D).A P value≤0.05 was considered statistically significant.RESULTS Kidney transplant recipients were classified as expressors(CYP3A51 carriers,n=35)and non-expressors(CYP3A5*3*3,n=60).Both groups were comparable for age,sex,and donor characteristics.Tacrolimus dose was comparable post-transplant except at 6 months and 12 months,where expressors required higher doses.Kidney function(creatinine and estimated GFR),NODAT,hypomagnesemia,and infections showed no significant differences between the two groups over 12 months of follow-up.Biopsy-proven acute rejection(BPAR)was found to be more in expressors(22.9%vs 13.3%,P=0.2340)though it was not found to be statistically significant.Nonexpressors had a significantly higher tacrolimus levels and C/D ratio at multiple follow-ups.CONCLUSION CYP3A5 expressors require higher tacrolimus doses to maintain therapeutic levels as compared to non-expressors.BPAR was higher in expressors but the difference was not significant.Graft function,infection rate,and NODAT were comparable irrespective of CYP3A5 expression status,emphasizing the importance of pretransplant CYP3A5 genotyping and therapeutic drug monitoring to guide tacrolimus dosing for individualized immunosuppressive management.
文摘目的:急性脑梗死病情进展迅速,常导致神经不可逆损伤,预后较差,需寻找相关预后标志物以了解预后情况。本研究旨在分析细胞色素P450(cytochrome P450,CYP)3A5基因多态性联合血清微RNA-543(microRNA-543,miR-543)预测急性脑梗死患者预后不良的价值。方法:选取2021年5月至2024年1月在郑州市第七人民医院诊断为急性脑梗死的176例患者作为研究对象,依据患者出院90 d后的门诊改良Rankin量表评分结果,将评分≤2的患者纳入预后良好组(n=92),评分>2的纳入预后不良组(n=84)。采用实时荧光定量PCR法检测治疗前血清miR-543水平,采用PCR法检测治疗前CYP3A5基因型,采用多因素Logistic回归分析影响急性脑梗死患者预后不良的因素,采用受试者操作特征(receiver operating characteristic,ROC)曲线分析CYP3A5基因rs776746位点GG基因型联合血清miR-543水平对急性脑梗死患者预后不良的预测价值。结果:CYP3A5基因rs776746位点上检出AA型、GA型、GG型3种基因型。预后不良组发病至溶栓时间长于预后良好组,血清miR-543水平、携带CYP3A5基因rs776746位点GG基因型及G等位基因、入院时美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分≥15和高血压患者比例均显著高于预后良好组(均P<0.001)。携带CYP3A5基因rs776746位点GG基因型和高miR-543水平是急性脑梗死患者预后不良的危险因素(均P<0.05)。CYP3A5基因rs776746位点GG基因型和血清miR-543水平单独及联合预测急性脑梗死患者预后不良的曲线下面积(area under the curve,AUC)分别为0.702、0.833、0.932,敏感度分别为52.38%、75.68%、92.86%,特异度分别为88.04%、78.33%、93.48%。结论:携带CYP3A5基因rs776746位点GG基因型和高miR-543水平均与急性脑梗死患者预后不良有关,二者联合可显著提高预测效能。
文摘目的评价基于细胞色素P450(CYP)3A5*1基因多态性指导肝移植术后他克莫司(FK506)个体化用药的安全性和有效性。方法分析连续入组的100例首次行肝移植术受者的临床资料,并随机分为实验组和对照组,每组各50例。实验组术前对供、受者进行CYP3A5基因检测,并根据CYP3A5*1基因型确定FK506用药方案。观察术后7、14、28 d以及3、6、9、12个月两组受者FK506目标血药浓度达标率、肝功能恢复正常率以及随访过程中FK506调整用量次数。记录两组受者1年移植物存活率,及急性排斥反应、感染、急性肾损伤、消化道症状、新发高血压、新发糖尿病、感冒、皮疹等并发症的发生率。结果两组受者术后7、14 d FK506目标血药浓度达标率比较,差异均有统计学意义(均为P<0.05)。两组术后28 d及3、6、9、12个月FK506目标血药浓度达标率及术后7个观察时间点肝功能恢复正常率比较,差异均无统计学意义(均为P>0.05)。两组受者随访期间FK506剂量调整次数比较,差异有统计学意义(P=0.021)。两组受者术后及随访期间1年移植物存活率和并发症发生率比较,差异均无统计学意义(均为P>0.05)。结论根据CYP3A5*1基因多态性指导肝移植术后FK506个体化用药是安全的,能在术后早期提高受者FK506目标血药浓度达标率,并且可以有效减少随访期间药量调整次数。
