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Abstract：
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 m2 [range, 91-113 ml/min/1.73 m2]) or felodipine (n = 20, GFR, 96 ml/min/1.73 m2 [range, 88-104 ml/min/1.73 m2]). 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 m2 (95% CI: -40 to 22 ml/min/1.73 m2), whereas that of the placebo group was 48 ml/min/1.73 m2 (95% confidence interval [CI]: -56 to 40 ml/min/1.73 m2). Thus, the difference between groups at 12 weeks was 17 ml/min/1.73 m2 (95% CI: 4-29 ml/min/1.73 m2; 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 m2 (95% CI: 0-24 ml/min/1.73 m2, 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.
In this prospective, randomized, double-blind trial, 39 LTX recipients were transplanted and received placebo (n = 19; GFR, 102 ml/min/1.73 m2 [range, 91-113 ml/min/1.73 m2]) or felodipine (n = 20, GFR, 96 ml/min/1.73 m2 [range, 88-104 ml/min/1.73 m2]). 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 m2 (95% CI: -40 to 22 ml/min/1.73 m2), whereas that of the placebo group was 48 ml/min/1.73 m2 (95% confidence interval [CI]: -56 to 40 ml/min/1.73 m2). Thus, the difference between groups at 12 weeks was 17 ml/min/1.73 m2 (95% CI: 4-29 ml/min/1.73 m2; 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 m2 (95% CI: 0-24 ml/min/1.73 m2, 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.
摘要：
钙通道阻滞剂可以改善肺移植（LTX）受体中钙调磷酸酶抑制剂引起的肾功能下降。我们假设术前和术后12周使用钙通道阻滞剂非洛地平治疗会减少肾小球滤过率（GFR）的下降。
在这个前景中，随机化，双盲审判,39例LTX受者移植并接受安慰剂(n=19；GFR，102毫升/分钟/1.73平方米[范围，91-113ml/min/1.73m2]）或非洛地平（n=20，GFR，96毫升/分钟/1.73平方米[范围，88-104毫升/分钟/1.73平方米])。术前治疗在术后滴定至10mg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GFR的变化，随访52周。
治疗组GFR的绝对平均下降为31ml/min/1.73m2（95％CI：-40至22ml/min/1.73m2），而安慰剂组为48ml/min/1.73m2(95%置信区间[CI]:-56~40ml/min/1.73m2).因此，12周时组间差异为17ml/min/1.73m2(95%CI:4-29ml/min/1.73m2;p=0.01).一半的患者无法完成3个月的主要随访，分析包括这些患者的意向治疗。52周后（治疗终止后40周），治疗效果维持在12ml/min/1.73m2（95％CI：0-24ml/min/1.73m2，p=0.05）。非洛地平组低血压登记天数明显高于安慰剂组(39天对13天,率比率：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）肾功能的更大保留相关。观察到的益处在1年内减弱，尽管观察到肾功能改善的趋势。
在这个前景中，随机化，双盲审判,39例LTX受者移植并接受安慰剂(n=19；GFR，102毫升/分钟/1.73平方米[范围，91-113ml/min/1.73m2]）或非洛地平（n=20，GFR，96毫升/分钟/1.73平方米[范围，88-104毫升/分钟/1.73平方米])。术前治疗在术后滴定至10mg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GFR的变化，随访52周。
治疗组GFR的绝对平均下降为31ml/min/1.73m2（95％CI：-40至22ml/min/1.73m2），而安慰剂组为48ml/min/1.73m2(95%置信区间[CI]:-56~40ml/min/1.73m2).因此，12周时组间差异为17ml/min/1.73m2(95%CI:4-29ml/min/1.73m2;p=0.01).一半的患者无法完成3个月的主要随访，分析包括这些患者的意向治疗。52周后（治疗终止后40周），治疗效果维持在12ml/min/1.73m2（95％CI：0-24ml/min/1.73m2，p=0.05）。非洛地平组低血压登记天数明显高于安慰剂组(39天对13天,率比率：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）肾功能的更大保留相关。观察到的益处在1年内减弱，尽管观察到肾功能改善的趋势。
