Conversion from Standard Calcineurin Inhibitor-Based Regimen to Noncalcineurin Inhibitor-Based Regimen in Kidney Transplantation: Systematic Review and Network Meta-Analysis

Background: Calcineurin inhibitors (CNIs) are main immunosuppression (IS) in kidney transplantation (KTx), but their nephrotoxicity remains a major concern. CNI-sparing strategies, such as conversion to sirolimus or belatacept, show potential. But, no standard regimen exists, largely due to the lack of direct comparisons. To address this, we conducted a systematic review and network meta-analysis of trials to guide IS conversion. Methods: We systematically searched MEDLINE for non-CNI conversion regimens with special focus on sirolimus- or belatacept-based regimen in adult KTx recipients. Across eligible studies, random-effects network meta-analyses were performed by frequentist methods to combine effects of individual conversion strategy on acute rejection (AR), graft loss, and patient death at 1-year post-conversion. Results: Of 245 references screened, 48 studies met eligibility criteria for inclusion. After excluding 9 studies were excluded (3 with only 6-month follow-up and 6 as extended follow-up report), 39 studies (n=7,271) were included in the quantitative synthesis. Compared to continued CNI use, conversion to sirolimus or belatacept was associated with higher AR risk at 1-year, odds ratio (OR)-95% confidence interval (CI): 1.37 (0.70-2.66) and OR 5.54 (1.98-15.50), respectively (Fig1). However, belatacept was associated with lower risks of graft loss and mortality. These unique effects, i.e., more kidney rejection but better graft and patient outcomes were not observed with sirolimus. Conclusion: Both sirolimus and belatacept conversion strategies increased rejection risk compared to the standard CNI regimen. However, belatacept was associated with improved graft and patient survival.