Risk of Metabolic Complications in Kidney Transplantation After Conversion From Calcineurin Inhibitor to mTOR Inhibitor: A Systematic Review and Meta-Analysis.

Abstract

Background: Mammalian target of rapamycin (mTOR) inhibitors (sirolimus/everolimus) have been used in calcineurin inhibitor (CNI)-sparing regimens in kidney transplantation to minimize CNI-induced vasoconstriction and nephrotoxicity. However, the incidence of metabolic complications after conversion from CNI to mTOR inhibitor is not fully documented. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials reporting incidences of new-onset diabetes after transplant (NODAT) and hypercholesterolemia in transplant recipients converted from CNI- to mTOR inhibitor-based immunosuppressive regimen. The endpoints included relative risks (RR) and incidences of these metabolic complications. Results: A total of 109 publications were identified, of which 9 trials (published from 2005 to 2012), involving a total of 2,312 patients, met the pre-defined eligibility criteria and were included in meta-analysis. The mean follow-up duration of these studies was 17 months. By using the random-effects model, the incidence of NODAT was calculated as 5.7% (95% confidence interval (CI) 3.42-9.3%) in patients receiving mTOR inhibitors in comparison to 4.9% (95% CI 3.2-7.6%) in those receiving CNI, while the incidence of hypercholesterolemia was 29.0% (95% CI, 15.6-47.3%) and 13.8% (95% CI, 4.8-33.5%), respectively. The conversion from CNI-based to mTOR inhibitor-based regimen was associated with a non-significantly increased risk of NODAT (RR, 1.32; 95% CI, 0.92-1.89, p=0.11) and a significantly increased risk of hypercholesterolemia (RR, 1.91; 95% CI, 1.26-2.93, p=0.007).Table: No Caption available.Table: No Caption available.Conclusions: To our knowledge, this is the first meta-analysis to evaluate the risk of metabolic complications associated with conversion from CNIs to mTOR inhibitors in post-kidney transplant recipients in contemporary immunosuppressive regimens. Since cardiovascular mortality is the leading cause of long-term graft loss, clinicians should be aware of these risks when switching from CNI to mTOR inhibitor.