Rehm B, Keller F, Mayer J, Stracke S
Department of Nephrology, Ulm University, Ulm, Germany.
Transplant Proc. 2006 Apr;38(3):711-3. doi: 10.1016/j.transproceed.2006.01.052.
Sirolimus-induced pneumonitis usually requires the complete cessation of sirolimus. Herein we have reported five cases of recovery from sirolimus pneumonitis after conversion from sirolimus to everolimus.
All five cases were comparable with regard to their clinical conditions. The ages were between 46 and 64 years. They had received kidney transplants 3 to 18 years earlier. In four cases, the reason for sirolimus therapy was toxicity due to calcineurin inhibitors on a transplant biopsy; three of the patients also displayed malignant tumors: renal cell carcinoma, spinocellular carcinoma, or melanoma. Their serum creatinine levels were elevated between 150 and 350 micromol/L. In all five cases, bronchoscopy disclosed lymphocytic pneumonitis and bronchiolitis obliterans. The immunosuppressive co-medications were prednisolone in three, azathioprine in one, and mycophenolate mofetil in four cases. The previous sirolimus dose was 1 to 4 mg/day, with sirolimus trough levels between 5 and 12 ng/mL. The patients were switched to everolimus at doses between 1 x 0.25 and 2 x 0.75 mg/day to achieve trough concentrations between 3 and 8 ng/mL. Pulmonary symptoms and radiological findings resolved completely within 1 to 4 weeks.
Everolimus is more hydrophilic by virtue of differing from sirolimus by one hydroxyl group. Sirolimus-induced pneumonitis improved after conversion to everolimus.
西罗莫司诱发的肺炎通常需要完全停用西罗莫司。在此，我们报告了5例从西罗莫司转换为依维莫司后西罗莫司肺炎恢复的病例。
所有5例患者的临床情况具有可比性。年龄在46至64岁之间。他们在3至18年前接受了肾移植。在4例中，西罗莫司治疗的原因是移植活检时钙调神经磷酸酶抑制剂的毒性；3例患者还患有恶性肿瘤：肾细胞癌、棘细胞癌或黑色素瘤。他们的血清肌酐水平升高至150至350微摩尔/升之间。在所有5例中，支气管镜检查均显示淋巴细胞性肺炎和闭塞性细支气管炎。免疫抑制联合用药方面，3例使用泼尼松龙，1例使用硫唑嘌呤，4例使用霉酚酸酯。之前的西罗莫司剂量为1至4毫克/天，西罗莫司谷浓度在5至12纳克/毫升之间。患者转换为依维莫司，剂量为每天1×0.25至2×0.75毫克，以达到3至8纳克/毫升的谷浓度。肺部症状和影像学表现在1至4周内完全缓解。
依维莫司因比西罗莫司多一个羟基而具有更强的亲水性。转换为依维莫司后，西罗莫司诱发的肺炎有所改善。
