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Meta-Analysis
. 2014 Jul;78(1):24-32.
doi: 10.1111/bcp.12289.

Impact of the reduction of calcineurin inhibitors on renal function in heart transplant patients: a systematic review and meta-analysis

Catherine Cornu  1 , Christophe Dufays, Ségolène Gaillard, François Gueyffier, Michel Redonnet, Laurent Sebbag, Ana Roussoulières, Christian A Gleissner, Jan Groetzner, Hans B Lehmkuhl, Luciano Potena, Lars Gullestad, Marcelo Cantarovich, Pascale Boissonnat
Affiliations
Meta-Analysis

Impact of the reduction of calcineurin inhibitors on renal function in heart transplant patients: a systematic review and meta-analysis

Catherine Cornu et al. Br J Clin Pharmacol. 2014 Jul.

Abstract

Aims: Calcineurin inhibitors (CNIs) taken after heart transplantation lead to excellent short-term outcomes, but long-term use may cause chronic nephrotoxicity. Our aim was to identify, appraise, select and analyse all high-quality research evidence relevant to the question of the clinical impact of CNI-sparing strategies in heart transplant patients.

Methods: We carried out a systematic review and meta-analysis of randomized controlled trials on CNI reduction in heart transplant recipients. Primary outcomes were kidney function and acute rejection after 1 year. Secondary outcomes included graft loss, all-cause mortality and adverse events.

Results: Eight open-label studies were included, with 723 patients (four tested de novo CNI reduction and four maintenance CNI reduction). Calcineurin inhibitor reduction did not improve creatinine clearance at 12 months 5.46 [-1.17, 12.03] P = 0.32 I(2) = 65.4%. Acute rejection at 12 months (55/360 vs. 52/332), mortality (18/301 vs. 15/270) and adverse event rates (55/294 vs. 52/281) did not differ between the low-CNI and standard-CNI groups. There was significant benefit on creatinine clearance in patients with impaired renal function at 6 months [+12.23 (+5.26, +18.82) ml min(-1) , P = 0.0003] and at 12 months 4.63 [-4.55, 13.82] P = 0.32 I(2) = 75%.

Conclusions: This meta-analysis did not demonstrate a favourable effect of CNI reduction on kidney function, but there was no increase in acute rejection. To provide a better analysis of the influence of CNI reduction patterns and associated treatments, a meta-analysis of individual patient data should be performed.

Keywords: calcineurin inhibitor; heart transplantation; meta-analysis; renal function.

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Figures

Figure 1
Figure 1
Flow diagram of studies
Figure 2
Figure 2
Forest plots for the primary outcome. (A) Creatinine clearance after 12 months. (B) Creatinine clearance after 6 months. (C) Acute rejection after 12 months
Figure 3
Figure 3
Subgroup analysis of patients with impaired renal function at inclusion. (A) Creatinine clearance at 12 months. (B) Acute rejection after 6 months.
See this image and copyright information in PMC

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