Sánchez-Fructuoso A I, Ruiz J C, Pérez-Flores I, Gómez Alamillo C, Calvo Romero N, Arias M
Department of Nephrology, Hospital Clínico San Carlos, Madrid, Spain.
Transplant Proc. 2010 Oct;42(8):3050-2. doi: 10.1016/j.transproceed.2010.07.083.
Inhibitors of mammalian target of rapamycin (mTORi) have been suggested as an alternative to calcineurin inhibitors (CNIs) to treat stable renal transplant recipients. However, their use has been significantly limited owing to a high incidence of side effects.
To compare the rate of dropout (mTORi elimination and CNI reintroduction) caused by side effects among renal transplant patients converted to everolimus (EVL) or sirolimus (SRL).
Between October 1999 and February 2010, 409 subjects were converted to an mTORi at least 3 months after transplantation, including 220 (53.8%) to EVL and 189 (46.2%) to SRL. Most patients were under CNI therapy. Patients were followed for a median of 35 months (interquartile range [IQR], 18-50 months).
mTORi treatment was prematurely eliminated due to adverse events in 112 patients. The median time between the initiation of mTORi and discontinuation was 5.7 months (IQR, 1.9-15.7 months; range, 0.2-48 months): 5.5 (IQR, 1.6-16.3) in the EVL group and 7.4 (IQR, 2.6-15.6) in the SRL group. In the EVL group, the drug was stopped in 69 patients (31.4%), and in the SRL group in 43 patients (22.8%; P=.051). The most important causes of discontinuation were severe infections (2.3% in EVL group and 4.8% in SRL group; P=.17), pneumonitis (6.8 % in EVL group and 4.8 in SRL group; P=.38), acute rejection episode (4.1% in EVL group and 1.6% in SRL group; P=.13), proteinuria (4.1% in EVL group and 1.6% in SRL group; P=.13), renal function deterioration (2.3% in EVL group and 2.1% in SRL group; P=.91), and severe dermal eruption (2.3% in EVL group and 0.5% in SRL group; P=.14).
Although the overall incidence discontinuations due to side effects was higher in the EVL group, there was no greater frequency of severe side effects, such as pneumonitis, proteinuria, acute rejection episodes, renal function deterioration, or dermal eruptions.
雷帕霉素哺乳动物靶点抑制剂（mTORi）已被提议作为钙调神经磷酸酶抑制剂（CNI）的替代药物，用于治疗稳定的肾移植受者。然而，由于其副作用发生率较高，其应用受到了显著限制。
比较转换为依维莫司（EVL）或西罗莫司（SRL）的肾移植患者中，因副作用导致的停药率（mTORi停用和CNI重新使用）。
在1999年10月至2010年2月期间，409名受试者在移植后至少3个月转换为mTORi，其中220名（53.8%）转换为EVL，189名（46.2%）转换为SRL。大多数患者接受CNI治疗。对患者进行了中位35个月的随访（四分位间距[IQR]，18 - 50个月）。
112名患者因不良事件过早停用mTORi。mTORi开始使用至停药的中位时间为5.7个月（IQR，1.9 - 15.7个月；范围，0.2 - 48个月）：EVL组为5.5个月（IQR，1.6 - 16.3个月），SRL组为7.4个月（IQR，2.6 - 15.6个月）。在EVL组，69名患者（31.4%）停药，SRL组有43名患者（22.8%）停药（P = 0.051）。停药的最重要原因是严重感染（EVL组为2.3%，SRL组为4.8%；P = 0.17）、肺炎（EVL组为6.8%，SRL组为4.8%；P = 0.38）、急性排斥反应（EVL组为4.1%，SRL组为1.6%；P = 0.13）、蛋白尿（EVL组为4.1%，SRL组为1.6%；P = 0.13）、肾功能恶化（EVL组为2.3%，SRL组为2.1%；P = 0.91）和严重皮疹（EVL组为2.3%，SRL组为0.5%；P = 0.14）。
尽管EVL组因副作用导致停药的总体发生率较高，但肺炎、蛋白尿、急性排斥反应、肾功能恶化或皮疹等严重副作用的发生频率并无差异。
