Felodipine and renal function in lung transplantation: A randomized placebo-controlled trial

Abstract

Background: 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).

Methods: 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.

Results: 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]).

Conclusions: 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.

Keywords: calcineurin inhibitors; calcium channel blockers; glomerular filtration rate; lung transplantation; renal function.