肾移植后吗替麦考酚酯联合低剂量他克莫司加皮质激素的应用

Application of mycophenolate mofetil combined with low-dose tacrolimus and corticosteroid regimen after renal transplantation

背景:足量吗替麦考酚酯联合低剂量他克莫司和皮质激素可能是目前针对肾移植受者的理想治疗方案,该方案因其具有低肾毒性以及较少的不良反应和较强的免疫抑制作用已在临床上开始逐渐普及。目的:以吗替麦考酚酯联合标准剂量他克莫司加皮质激素为对照,评估吗替麦考酚酯联合低剂量他克莫司加皮质激素在肾移植患者中的疗效和安全性。方法:210例首次接受单一器官同种异体移植的肾移植成人受者被随机分配到他克莫司标准剂量组(n=104)和他克莫司低剂量组(n=106),并接受12个月的治疗。主要疗效指标包括肾移植后第12个月慢性移植物损伤指数(CADI)以及肾小球滤过率;次要疗效指标主要包括急性排斥反应发生率、治疗失败率以及患者和移植肾的存活率等;同时对新发移植后糖尿病,新发高血压,新发高血脂等安全性指标进行评价。结果与结论:两组绝大多数患者使用了足量的吗替麦考酚酯(1.5g/d及以上)。在他克莫司剂量方面,他克莫司标准剂量组大多数受试者的实际血药浓度水平偏低,与低剂量组的实际血药浓度水平类似,由此反映了吗替麦考酚酯联合低剂量他克莫司和皮质激素方案已广泛为目前临床医师接受和使用。因此,两组也表现出类似的疗效和安全性:他克莫司标准剂量组和低剂量组肾移植后12个月肾脏病理改变的平均CADI评分分别为1.82分和2.13分(P=0.0813),平均肾小球滤过率分别为77.08mL/min和80.12mL/min(P=0.7949),急性排斥反应发生率分别为2.6%和5.2%(P=0.6812),患者和移植肾存活率分别高达100%和99.1%(P=1.0000)。在安全性方面,他克莫司标准剂量组和低剂量组新发移植后糖尿病的比例分别为2.9%和1.9%,新发高血脂的比例分别为2.9%和3.8%。结果显示在吗替麦考酚酯联合他克莫司和皮质激素的肾移植免疫抑制治疗方案中,足量吗替麦考酚酯的使用,可以减少他克莫司的剂量,在保持较强的免疫抑制作用即成功地降低急性排斥反应发生率的同时,显著减少他克莫司所致的肾毒性、高血脂和新发糖尿病等不良反应,较好地达到了疗效和毒性间的平衡。

BACKGROUND： Sufficient dose of mycophenolate mofetil combined with low-dose tacrolimus and corticosteroid regimen may be an ideal treatment option for renal transplant recipients, and the regimen has been widely used in clinic due to its low nephrotoxicity, few adverse reactions and strong immunosupprassive effects. OBJECTIVE： To investigate the efficacy and safety of mycophenolate mofetil combined with low-dose tacrolimus and corticosteroid regimen in renal transplantation patients with the control of mycophenolate mofetil combined with standard-dose tacrolimus and corticosteroid. METHODS： A total of 210 patients receiving a single-organ renal allograft were randomly divided into standard-dose tacrolimus group （n=104） and low-dose tacrolimus group （n=106）. Individual patients were treated for 12 months. The primary efficacy endpoints were the chronic allograff damage index and glomerular filtration rate at 12 months after transplantation. The secondary efficacy end points mainly included the acute rejection rate treatment failure rate, and the survival rate of patient and transplant kidney. The safety parameters such as new onset of post-transplantation diabetes mellitus, hypertension and hypedipidemia were also evaluated. RESULTS AND CONCLUSION： The vast majorities of patients were administrated with sufficient dose of mycophenolate mofetil （1.5 g/d or above） in two groups. The majority of the patients in standard-dose tacrolimus group had the mean trough level below the protocol-defined, which led to the similar mean trough level between standard-dose and low-dose tacrolimus group. These could also confirm that the regimen of mycophenolate mofetil combined with low-dose tacrolimus and corticosteroid had been wildly accepted and used by clinicians. The efficacy and safety of two groups were similar. The mean chronic allograft damage index of the renal pathological changes at 12 months after transplantation in standard-dose and low-dose tacrolimus group were 1.82 and 2.13 respectively （P=-0.081 3）, the mean glomerular filtration rates were 77.08 mL/min and 80.12 mL/min （P=0.794 9）, acute rejection rates were 2.6% and 5.2% （P=-0.681 2）, and the survival rates of patients and transplant kidney were 100% and 99.1% （P=-1.000 0）. The rates of new onset of post-transplantation diabetes mellitus in the standard-dose and low-dose tacrolimus group were 2.9% and 1.9%, and the rates of hyperlipidemia were 2.9% and 3.8%, respectively. For the regimen of mycophenolate mofetil combined with tacrolimus and corticosteroid, the utilization of sufficient dose of mycophenolate mofetil could reduce the dose of tacrolimus, thereby significantly reducing the nephrotoxicity, hypedipidemia and new onset of post-transplantation diabetes mellitus caused by tacrolimus and achieving a good balance of efficacy and toxicity when maintaining a strong immune inhibition and reducing the acute rejection incidence successfully.