Di Benedetto Fabrizio, Di Sandro Stefano, De Ruvo Nicola, Spaggiari Mario, Montalti Roberto, Ballarin Roberto, Cappelli Gianni, Gerunda Giorgio E
Liver and Multivisceral Transplant Center, University of Modena and Reggio Emilia, Modena, Italy.
J Clin Gastroenterol. 2009 Mar;43(3):280-6. doi: 10.1097/MCG.0b013e3181739ff8.
Among the adverse effects of different calcineurin inhibitors (CIs), nephrotoxicity is the most common (incidence: 18.1% at 13 y from liver transplantation) and depends on a variable degree of tubular-interstitial injury accompanied by focal glomerular sclerosis. A new immunosuppressive drug was introduced in solid organ transplant management, Sirolimus (SRL). It is a nonnephrotoxic immunosuppressor.
Twenty-six patients who developed nephrotoxicity owing to CIs, showing an increment of serum creatinine levels (>1.8 mg/dL) were switched to SRL monotherapy, initially at a dosage between 3 and 5 mg/d, and subsequently adapted to achieve trough level between 8 to 10 ng/mL.
Patients were followed-up for a mean period of 40.3 months (range, 8.4 to 76.7) from liver transplantation. Mean follow-up after switch was 27.5 months (range, 2 to 71.2). Immunosuppression therapy was converted after a mean period of 12.8 months (range, 0.2 to 43.4). Serum creatinine, urea, and estimated glomerular filtration rate were significantly improved.
Patients developing renal dysfunction after liver transplantation may be successfully treated by conversion from CI to SRL. Hypertriglyceridemia and hypercholesterolemia represent the principal side effects from SRL, but are treatable. Furthermore, SRL can significantly improve glucose tolerance.
在不同的钙调神经磷酸酶抑制剂（CI）的不良反应中，肾毒性最为常见（发生率：肝移植后13年时为18.1%），且取决于不同程度的肾小管间质损伤并伴有局灶性肾小球硬化。一种新的免疫抑制药物西罗莫司（SRL）被引入实体器官移植管理中。它是一种无肾毒性的免疫抑制剂。
26例因CI导致肾毒性、血清肌酐水平升高（>1.8mg/dL）的患者改为接受SRL单药治疗，初始剂量为3至5mg/d，随后进行调整以使谷浓度达到8至10ng/mL。
患者从肝移植开始平均随访40.3个月（范围8.4至76.7个月）。转换治疗后平均随访27.5个月（范围2至71.2个月）。免疫抑制治疗平均在12.8个月（范围0.2至43.4个月）后转换。血清肌酐、尿素和估计肾小球滤过率均有显著改善。
肝移植后出现肾功能障碍的患者从CI转换为SRL治疗可能会取得成功。高甘油三酯血症和高胆固醇血症是SRL的主要副作用，但可治疗。此外，SRL可显著改善糖耐量。
