Infections After Kidney Transplantation: A Comparison of MTOR-Is and CNIs As Basic Immunosuppressants. A Systematic Review and Meta-analysis

Background: Side effects of the immunosuppressive therapy after solid organ transplantation are well known. Recently, significant benefits were shown for mTOR-Is with respect to certain viral infections in comparison with CNIs. However, reported total incidences of infections under mTOR-Is vs CNIs are usually not different. This raises the question to additional differences between these immunosuppressants regarding development and incidence of infections.

Methods: The current literature was searched for prospective randomized controlled trials in renal transplantation. There were 954 trials screened of which 19 could be included (9861 pts.). The 1-year incidence of infections, patient and graft survival were assessed in meta-analyses.

Results: Meta-analysis on 1-year incidence of infections showed a significant benefit of an mTOR-I based therapy when combined with a CNI vs CNI-based therapy alone (OR 0.76). There was no difference between mTOR-I w/o CNI and CNI therapy (OR 0.97). For pneumonia, a significant disadvantage was seen only for mTOR-I monotherapy compared to CNI's (OR 2.09). The incidence of CMV infections was significantly reduced under mTOR-I therapy (combination with CNI: OR 0.30; mTOR w/o CNI: OR: 0.46). There was no significant difference between mTOR-I and CNI therapy with respect to patient survival (mTOR-I w/o CNI vs CNI: OR 1.22; mTOR-I with CNI vs CNI: OR 0.86). Graft survival was negatively affected by mTOR-I monotherapy (OR 1.52) but not when combined with a CNI (OR 0.97).

Conclusion: Following renal transplantation the incidence of infections is lower when mTOR-Is are combined with a CNI compared to a standard CNI therapy. Pneumonia occurs more often under mTOR-I w/o CNI.