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

doi:10.3969/j.issn.2095-4344.2013.05.003

Abstract

Abstract:

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 immunosuppressive 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 allograft 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 hyperlipidemia 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, hyperlipidemia 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.

Key words: organ transplantation, kidney transplantation, mycophenolate mofetil, tacrolimus, low doses, standard dose, acute rejection, chronic allograft damage index, diabetes after transplantation, glomerular filtration rate, survival rate, National Natural Science Foundation of China

CLC Number:

R318

Ji Shu-ming1, Chen Jiang-hua2, Tan Jian-ming3, Zhang Xiao-dong4, Zhu Tong-yu5, Chen Li-zhong. Application of mycophenolate mofetil combined with low-dose tacrolimus and corticosteroid regimen after renal transplantation[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(5): 777-784.

Figures/Tables 4

2.3 临床疗效评价肾移植第12个月肾脏病理改变的CADI评分平均1.97分，其中他克莫司标准剂量组的平均CADI评分为1.82分，他克莫司低剂量组的平均CADI评分为2.13分，两组比较差异无显著性意义(P=0.081 3)。肾移植第12个月的平均肾小球滤过率为 78.56 mL/min，其中他克莫司标准剂量组平均肾小球滤过率为77.08 mL/min，他克莫司低剂量组平均肾小球滤过率为80.12 mL/min，两组比较差异无显著性意义(P=0.794 9)。肾移植后各个时间点平均肾小球滤过率的变化见图2。肾移植后6个月和12个月急性排斥反应发生率都仅为3.9%，他克莫司标准剂量组和低剂量组分别为2.6%和5.2%，两组差异无显著性意义(P=0.681 2)。肾移植后6个月内和12个月内均未发生移植物丢失。移植后6个月内未出现死亡病例，而移植后12个月内，他克莫司低剂量组1例患者死亡。患者和移植物存活率均为99.5%，其中他克莫司标准剂量组和低剂量组人存活率分别为100%和99.1%，两组差异无显著性意义(P=1.000)。 17例患者(8.1%)肾移植后12个月内治疗失败，其中他克莫司标准剂量组为10例(9.6%)，他克莫司低剂量组为7例(6.6%)，两组差异无显著性意义(P=0.458 6)。在治疗失败的患者中，1例患者死亡，16例患者使用了研究方案对该治疗组规定以外的其他维持治疗的免疫抑制药物，其中8例使用了环孢素，6例使用了咪唑立宾，1例使用了来氟米特和1例使用了麦考酚钠肠溶片。 2.4 安全性评价　仅有8.6%的患者(他克莫司标准剂量组8.7%，他克莫司低剂量组8.5%)出现白细胞计数减少，2.4%的患者(他克莫司标准剂量组2.9%，他克莫司低剂量组1.9%)新发糖尿病，3.3%的患者(他克莫司标准剂量组2.9%，他克莫司低剂量组3.8%)新发高血脂，3.8%的患者出现感染(他克莫司标准剂量组3.8%，他克莫司低剂量组3.8%)，0.5%的患者出现机会性感染(他克莫司标准剂量组无，他克莫司低剂量组0.9%)，所有患者均未出现贫血、中性粒细胞减少、新发血管疾病、新发高血压、新发恶性肿瘤以及移植后最初6个月需要干预的囊状淋巴瘤。出现不良事件的发生率为34.8%(他克莫司标准剂量组31.7%，他克莫司低剂量组37.7%)，最常见的治疗出现不良事件为谷丙转氨酶升高(10.5%)，白细胞计数减少(8.6%)和腹泻(5.7%)。绝大多数治疗出现不良事件为轻度或中度。 6例受试者(2.9%)[他克莫司标准剂量组1例(1.0%)，他克莫司低剂量组5例(4.7%)]报告发生严重不良事件，分别为心血管意外1例、移植肾破裂1例、急性肾移植排斥2例、移植肾输尿管梗阻1例和巨细胞病毒感染1例，其中3例严重不良事件被研究者认为与研究药物相关，分别为急性肾移植排斥2例和巨细胞病毒感染1例。他克莫司低剂量组1例受试者因发生心血管意外严重不良事件导致死亡。本研究临床实验室检查和生命体征均未发现临床显著意义的变化。"

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