Meta-analysis of calcineurin-inhibitor-sparing regimens in kidney transplantation

Abstract

Calcineurin-inhibitor-sparing strategies in kidney transplantation may spare patients the adverse effects of these drugs, but the efficacy of these strategies is unknown. Here, we conduct a meta-analysis to assess outcomes associated with reducing calcineurin inhibitor exposure from the time of transplantation. We search Medline, Embase, and Cochrane Register of Controlled Trials for randomized controlled trials published between 1966 and 2010 that compared de novo calcineurin-inhibitor-sparing regimens to calcineurin-inhibitor-based regimens. In this analysis, we include 56 studies comprising data from 11337 renal transplant recipients. Use of the contemporary agents belatacept or tofacitinib, in combination with mycophenolate, decreased the odds of overall graft failure (OR 0.61; 95% CI 0.39-0.96; P = 0.03). Similarly, minimization of calcineurin inhibitors in combination with various induction and adjunctive agents reduces the odds of graft failure (OR 0.73; 95% CI 0.58-0.92; P = 0.009). Conversely, the use of inhibitors of mammalian target of rapamycin (mTOR), in combination with mycophenolate, increases the odds of graft failure (OR 1.43; 95% CI 1.08-1.90; P = 0.01). Calcineurin-inhibitor-sparing strategies are associated with less delayed graft function (OR 0.89; 95% CI 0.80-0.98; P = 0.02), improved graft function, and less new-onset diabetes. The more contemporary protocols did not seem to increase rates of acute rejection. In conclusion, this meta-analysis suggests that reducing exposure to calcineurin inhibitors immediately after kidney transplantation may improve clinical outcomes.

Figure 1.

PRISMA flow diagram identifying de novo CNI sparing trials for inclusion in meta-analysis.

Figure 2.

Forest plot of overall graft survival with CNI avoidance strategies using mTORI/mycophenolate combination.

Figure 3.

Forest plot of overall graft survival with CNI avoidance strategies using new agents (belatacept or tofacitinib).

Figure 4.

Forest plot of overall graft survival with CNI minimization strategies.

Figure 5.

Figure plot showing episodes of delayed graft function comparing all CNI sparing studies with CNI-based regimens.

Figure 6.

Figure plot showing graft function for all CNI sparing versus CNI-based studies.

Figure 7.

Forest plot of episodes of new onset diabetes after transplantation between CNI sparing and CNI-based arms (diagnosis by guidelines).