Oslo University Hospital Rikshospitalet, Oslo, Norway.
J Heart Lung Transplant. 2012 Mar;31(3):259-65. doi: 10.1016/j.healun.2011.12.010.
The NOCTET (NOrdic Certican Trial in HEart and lung Transplantation) trial demonstrated that everolimus improves renal function in maintenance thoracic transplant (TTx) recipients. Nevertheless, introduction of everolimus is not recommended for patients with advanced renal failure. We evaluated NOCTET data to assess everolimus introduction amongst TTx recipients with advanced renal failure.
This 12-month multicenter Scandinavian study randomized 282 maintenance TTx recipients to everolimus introduction with calcineurin inhibitor (CNI) reduction or standard CNI therapy. The measured glomerular filtration rate (mGFR) was noted at baseline and after 1-year using Cr-ethylenediaminetetraacetic acid clearance.
In 21 patients with a baseline mGFR of 20 to 29 ml/min/1.73 m(2), renal function improved in the everolimus group compared with the control group ((ΔmGFR 6.7 ± 9.0 vs -1.6 ± 5.1 ml/min/1.73 m(2); p = 0.03). Amongst 173 patients with moderate renal impairment (mGFR 30-59 ml/min/1.73 m(2)), renal function improvement was also greater amongst everolimus patients than in controls (ΔmGFR 5.1 ± 11.1 vs -0.5 ± 8.7 ml/min/1.73 m(2); p < 0.01). In 55 patients with mGFR 60 to 89 ml/min/1.73 m(2), mGFR did not change significantly in either group. Improvement in mGFR was limited to patients with a median time since TTx of less than 4.6 years and was also influenced by CNI reduction during the study period.
Everolimus introduction and reduced CNI significantly improved renal function amongst maintenance TTx patients with pre-existing advanced renal failure. This beneficial effect was limited to patients undergoing conversion in less than 5 years after TTx, indicating a window of opportunity that is appropriate for pharmacologic intervention with everolimus.
NOCTET（北欧心脏和肺脏移植认证试验）试验表明依维莫司可改善维持性胸部移植（TTx）受者的肾功能。然而，对于肾功能衰竭的患者，不建议使用依维莫司。我们评估了 NOCTET 数据，以评估依维莫司在肾功能衰竭的 TTx 受者中的引入。
这是一项为期 12 个月的多中心斯堪的纳维亚研究，将 282 例接受维持性 TTx 的患者随机分为依维莫司组（与钙调神经磷酸酶抑制剂[CNI]减少联合使用）和标准 CNI 治疗组。在基线和 1 年后，通过 Cr-乙二胺四乙酸清除率测量肾小球滤过率（mGFR）。
在基线 mGFR 为 20-29 ml/min/1.73 m2 的 21 例患者中，与对照组相比，依维莫司组的肾功能有所改善（mGFR 变化：6.7±9.0 vs -1.6±5.1 ml/min/1.73 m2；p=0.03）。在 173 例中度肾功能不全（mGFR 30-59 ml/min/1.73 m2）的患者中，依维莫司组的肾功能改善也大于对照组（mGFR 变化：5.1±11.1 vs -0.5±8.7 ml/min/1.73 m2；p<0.01）。在 55 例 mGFR 为 60-89 ml/min/1.73 m2 的患者中，两组的 mGFR 均无显著变化。mGFR 的改善仅限于 TTx 后中位时间<4.6 年的患者，并且也受到研究期间 CNI 减少的影响。
依维莫司的引入和 CNI 的减少可显著改善维持性 TTx 患者的肾功能，这些患者存在预先存在的肾功能衰竭。这种有益作用仅限于 TTx 后<5 年内进行转换的患者，表明存在适当的机会窗，可进行依维莫司的药物干预。
