Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients.Hahn, D. et al.
Cochrane Database of Systematic Reviews 2019; 12: CD004290.
The primary aim of this study was to assess the benefits and harms of using sirolimus and everolimus (TOR-I) in primary immunosuppressive regimens for recipients of kidney transplant over short and long-term.
The Cochrane Kidney and Transplant Register of Studies, which included studies identified from MEDLINE, EMBASE, CENTRAL, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov and conference proceedings, was searched up to September 20, 2019. Three independent authors were involved in assessment of the study eligibility, methodological quality and extraction of data.
70 studies were included in the analysis.
The primary outcomes included death (all causes), death-censored graft loss, all cause graft loss, acute rejection, incidence of cytomegalovirus (CMV), all malignancies, number needing to change treatment, and all adverse wound outcomes and lymphocoele. The secondary outcomes included graft function, number of BK virus infections, lymphoma/post transplant lymphoproliferative disorder (PTLD), incidence of treatment-related adverse reactions related to TOR-I, and new-onset diabetes mellitus.
This is a thorough and well-conducted Cochrane review from the Cochrane Kidney and Transplant Group, it is an update of their 2006 review of the same topic. Multiple databases were searched following a pre-specified protocol, and including trials registries. 70 studies were included, with a total 17462 randomised patients. Data was extracted independently by three separate authors, but it is not clear if the studies were split three ways, or data was extracted in triplicate and then checked. Risk of bias assessment was done using the Cochrane Collaboration tool, blinding of participants and personnel was particularly poor but blinding of outcome assessment was excellent overall. Funnel plots were produced to assess for risk of publication bias. The results of this review suggest that TOR inhibitors with antimetabolites should not be used as the initial immune suppression in renal transplantation due to a higher risk of acute rejection when compared to CNI with antimetabolite. TOR inhibitors alongside CNI may offer an alternative initial immune suppression, though wound complications and a need to change regimen are more common than when using the combination of CNI with antimetabolite.