早期和晚期心脏移植受者转换为依维莫司免疫抑制治疗后的肾功能恢复：一项为期12个月的分析。

Renal recovery after conversion to an everolimus-based immunosuppression in early and late heart transplant recipients: a 12-month analysis.

作者信息

Michel Sebastian, Bigdeli Amir Khosrow, Hagl Christian, Meiser Bruno, Kaczmarek Ingo

机构信息

Department of Cardiac Surgery, Klinikum Grosshadern, Ludwig Maximilians University, D-81377 Munich, Germany.

出版信息

Exp Clin Transplant. 2013 Oct;11(5):429-34. doi: 10.6002/ect.2013.0036.

DOI:10.6002/ect.2013.0036

PMID:24128136

Abstract

OBJECTIVES

Calcineurin inhibitor-induced nephrotoxicity reduces long-term patient survival after heart transplant. Proliferation signal inhibitors, in combination with or replacing calcineurin inhibitors, may preserve or improve renal function. We evaluated the effect of calcineurin inhibitor-reduction and withdrawal in everolimus-based immunosuppression on renal function after a heart transplant.

MATERIALS AND METHODS

Twenty-four patients with creatinine clearance < 1 mL/s (60 mL/min) were switched from tacrolimus and mycophenolate mofetil to low-dose tacrolimus/everolimus if their heart transplant was ≤ 1 year ago (group 1, n=13) and to everolimus/mycophenolate mofetil if their heart transplant was > 1 year ago (group 2, n=11). Serum creatinine levels and calculated creatinine clearance were analyzed up to 12 months after conversion.

RESULTS

The switch in immunosuppression was associated with a significant decrease/increase of serum creatinine/creatinine clearance in both groups between baseline and month 12 (group 1, creatinine, 221.0 ± 70.7 to 159.1 ± 44.2 μmol/L (2.5 ± 0.8 to 1.8 ± 0.5 mg/dL); creatinine clearance, 0.75 ± 0.45 to 1.01 ± 0.50 mL/s (45.1 ± 26.7 to 60.5 ± 29.7 mL/min) (P < .01 each); group 2, creatinine, 247.5 ± 79.6 to 159.1 ± 44.2 μmol/L (2.8 ± 0.9 to 1.8 ± 0.5 mg/dL), creatinine clearance, 0.57 ± 0.23 to 0.93 ± 0.33 mL/s (34.1 ± 13.8 to 55.7 ± 19.6 mL/min) [P < .05 each]) with no significant group difference in the creatinine and the creatinine clearance levels after switching. No acute rejections or deaths occurred during the 12-month follow-up. Four patients (36.4%) from group 2 and 1 patient (7.7%) from group 1 discontinued everolimus because of adverse events.

CONCLUSIONS

Everolimus allows calcineurin inhibitor-reduction and withdrawal after a heart transplant, resulting in improved renal function. However, adverse effects are common and lead to a high reconversion rate.

摘要

目的

钙调神经磷酸酶抑制剂诱导的肾毒性会降低心脏移植患者的长期生存率。增殖信号抑制剂与钙调神经磷酸酶抑制剂联合使用或替代钙调神经磷酸酶抑制剂，可能会维持或改善肾功能。我们评估了在以依维莫司为基础的免疫抑制方案中减少和停用钙调神经磷酸酶抑制剂对心脏移植后肾功能的影响。

材料和方法

24例肌酐清除率<1 mL/s（60 mL/min）的患者，如果心脏移植时间≤1年（1组，n = 13），则从他克莫司和霉酚酸酯转换为低剂量他克莫司/依维莫司；如果心脏移植时间>1年（2组，n = 11），则转换为依维莫司/霉酚酸酯。转换后长达12个月分析血清肌酐水平和计算的肌酐清除率。

结果

两组在基线和第12个月之间免疫抑制方案的转换均与血清肌酐/肌酐清除率的显著降低/升高相关（1组，肌酐，221.0±70.7至159.1±44.2 μmol/L（2.5±0.8至1.8±0.5 mg/dL）；肌酐清除率，0.75±0.45至1.01±0.50 mL/s（45.1±26.7至60.5±29.7 mL/min）（每项P<.01）；2组，肌酐，247.5±79.6至159.1±44.2 μmol/L（2.8±0.9至1.8±0.5 mg/dL），肌酐清除率，0.57±0.23至0.93±0.33 mL/s（34.1±13.8至55.7±19.6 mL/min）[每项P<.05]），转换后肌酐和肌酐清除率水平无显著组间差异。在12个月的随访期间未发生急性排斥反应或死亡。2组中的4例患者（36.4%）和1组中的1例患者（7.7%）因不良事件停用依维莫司。