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

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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.

Section snippets

Study design and patients

The trial was an investigator-initiated, randomized, double-blind, placebo-controlled, clinical trial conducted at a national lung transplant center. The program has been described in detail previously.16 Briefly, recipients received induction therapy with anti-thymocyte globulin (1.5 mg/kg daily) for the first 3 days. Azathioprine (1.5 mg/kg) was initiated at admission and cyclosporine (Sandimmun Neoral, Novartis Healthcare AG, Basel, Switzerland) was initiated on the first post-operative day

Results

A total of 41 patients underwent randomization; 2 had their transplant procedure canceled after randomization but were rerandomized and transplanted later, 20 were assigned to receive felodipine, and 19 to receive placebo (Figure 1). As shown in Table 1, the baseline characteristics were similar in the 2 groups except for a higher s-albumin in the felodipine group, a difference that disappeared 1 week after transplantation. The minimum follow-up time was 365 days.

The median daily dose of

Discussion

In this randomized placebo-controlled trial, 12 weeks of intended treatment with the calcium channel blocker felodipine reduced the decline in the GFR at 12 weeks after LTX by 35%. This result was obtained with only 50% patient compliance; only pre-operatively all patients received intended treatment (Figure 2). The pre-operative initiation of the treatment and the peri-operative blood pressure response indicated by the need for more inotropy in the felodipine group during surgery may have been

Disclosure statement

Dr Hornum was supported by an unrestricted grant from the Helen and Ejnar Bjørnow Foundation. Dr Perch reports grants from Roche, non-financial support from Boeringer Ingelheim, personal fees from Novartis, BTG, outside the submitted work. The rest of the authors have no conflicts of interest.

The authors thank the patients who participated in this study. The authors also thank Laboratory Technician Andreas Haltorp and Study Nurse Jytte Grarup and Helle Corinth for their skillful work.

Mads

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