Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Department of Cardiology, Section for Lung Transplantation, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
J Heart Lung Transplant. 2020 Jun;39(6):541-550. doi: 10.1016/j.healun.2020.01.1342. Epub 2020 Feb 13.
Calcium channel blockers may ameliorate the decline in renal function caused by calcineurin inhibitors in lung transplantation (LTX) recipients. We hypothesized that pre-operative and 12-week post-operative treatment with the calcium channel blocker felodipine would reduce the decline in glomerular filtration rate (GFR).
In this prospective, randomized, double-blind trial, 39 LTX recipients were transplanted and received placebo (n = 19; GFR, 102 ml/min/1.73 m [range, 91-113 ml/min/1.73 m]) or felodipine (n = 20, GFR, 96 ml/min/1.73 m [range, 88-104 ml/min/1.73 m]). Pre-operative treatment was titrated post-operatively to 10 mg or the maximum tolerable dose. The primary end-point was the change in GFR using Cr-51-labeled EDTA from LTX to 12 weeks thereafter, and follow-up was 52 weeks.
The treatment group showed an absolute mean decline in GFR of 31 ml/min/1.73 m (95% CI: -40 to 22 ml/min/1.73 m), whereas that of the placebo group was 48 ml/min/1.73 m (95% confidence interval [CI]: -56 to 40 ml/min/1.73 m). Thus, the difference between groups at 12 weeks was 17 ml/min/1.73 m (95% CI: 4-29 ml/min/1.73 m; p = 0.01). Half of the patients were unable to complete the 3-month primary follow-up, and the analysis includes these patients by intention-to-treat. After 52 weeks (40 weeks after termination of treatment), the treatment effect was maintained at 12 ml/min/1.73 m (95% CI: 0-24 ml/min/1.73 m, p = 0.05). The number of days with registered hypotension was significantly higher in the felodipine group than in the placebo group (39 days vs 13 days, rate ratio: 2.9 [95% CI: 1.5-5.3]).
Use of felodipine in select patients was associated with greater preservation in renal function early (90 days) after LTX. The observed benefits were attenuated by 1 year, although trends in better renal function were noted.
钙通道阻滞剂可能改善肺移植（LTX）受者中环孢素抑制剂引起的肾功能下降。我们假设术前和术后 12 周用钙通道阻滞剂非洛地平治疗可降低肾小球滤过率（GFR）的下降。
在这项前瞻性、随机、双盲试验中，39 名 LTX 受者接受移植并接受安慰剂（n=19；GFR，102 ml/min/1.73 m [范围，91-113 ml/min/1.73 m]）或非洛地平（n=20，GFR，96 ml/min/1.73 m [范围，88-104 ml/min/1.73 m]）。术前治疗在术后滴定至 10 mg 或最大耐受剂量。主要终点是使用 Cr-51 标记的 EDTA 从 LTX 到 12 周后的 GFR 变化，随访时间为 52 周。
治疗组 GFR 绝对平均下降 31 ml/min/1.73 m（95%CI：-40 至 22 ml/min/1.73 m），而安慰剂组为 48 ml/min/1.73 m（95%置信区间[CI]：-56 至 40 ml/min/1.73 m）。因此，12 周时两组之间的差异为 17 ml/min/1.73 m（95%CI：4-29 ml/min/1.73 m；p=0.01）。一半的患者无法完成 3 个月的主要随访，分析包括这些按意向治疗的患者。52 周（治疗结束后 40 周）后，治疗效果仍保持在 12 ml/min/1.73 m（95%CI：0-24 ml/min/1.73 m，p=0.05）。非洛地平组记录低血压天数明显高于安慰剂组（39 天 vs 13 天，比率比：2.9 [95%CI：1.5-5.3]）。
在某些患者中使用非洛地平与 LTX 后早期（90 天）肾功能的更好保存相关。虽然观察到肾功能更好的趋势，但 1 年后观察到的益处减弱。
