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

Catherine Cornu (1) , C. Dufays , Ségolène Gaillard , François Gueyffier (1) , M. Redonnet , Laurent Sebbag (2) , A. Roussoulieres , C. A. Gleissner , J. Groetzner , H. B. Lehmkuhl , L. Potena , L. Gullestad , M. Cantarovich , P. Boissonnat

1 Evaluation et modélisation des effets thérapeutiques
2 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition

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.

Mots clés: Drug; Dose-Response Relationship; Graft Rejection/*chemically induced/epidemiology; *Heart Transplantation/adverse effects/mortality; Randomized Controlled Trials as Topic; Humans; Cause of Death; Creatinine/metabolism; Kidney Diseases/*chemically induced/epidemiology/*physiopathology; Postoperative Complications/*chemically induced/epidemiology/physiopathology; Calcineurin Inhibitors/*administration & dosage/*adverse effects/therapeutic use

Domaines: Sciences du Vivant [q-bio]

Catherine Cornu, C. Dufays, Ségolène Gaillard, François Gueyffier, M. Redonnet, et al.. Impact of the reduction of calcineurin inhibitors on renal function in heart transplant patients: a systematic review and meta-analysis. British Journal of Clinical Pharmacology, 2014, 78 (1), pp.24-32. ⟨10.1111/bcp.12289⟩. ⟨hal-01859376⟩