Background: Long-term exposure to Calcineurin-Inhibitors (CNIs) has been associated with impaired renal function.

Objective: To obtain parameter estimates of the relative renal safety of commonly used treatment regimens for immunosuppression (IS) post-liver transplant (LTx).

Methods: We conducted a systematic review of the published literature for randomised controlled trials and observational studies reporting renal function (RF) as an outcome of IS regimens post-LTx. A fixed-effect mixed-treatment network analysis was used to compute pooled estimates of the change in RF at 12 months from baseline (day of LTx).

Results: A total of 1,043 publications were identified, of which 77 met the pre-defined eligibility criteria. Data on mean ± standard deviation estimated glomerular filtration rates (eGFR) at baseline and 12 months available for 11 publications (8 clinical and 3 observational studies) allowed a connected network of 8 IS strategies involving 1,506 patients.

Preliminary analyses showed no significant difference in change from baseline between cyclosporine (CsA) and Tacrolimus (Tac) monotherapies (Figure 1) or in combination with azathioprine (AZA). The addition of mycophenolate mofetil (MMF) to Tac significantly improved eGFR vs. Tac monotherapy; the strategy with delayed-dose of Tac was associated with the greatest improvement (41.83 mL/min; 95% Credible Interval [34.72; 48.85]). However, reduced Tac + MMF did not appear to preserve renal function as well as Standard Tac + MMF at 12-months (-15.47 mL/min; 95% Credible Interval [-22.69; -8.27]).

Conclusion: To the best of our knowledge this is the first indirect mixed treatment comparison that attempts to formally analyse the effect of different IS strategies on RF in LTx. More research is required to investigate the full effect of the mix of traditional CNI-based therapies on RF including the effect of more recent IS agents as more data become available.

Bianic, F.: Other, Neoral (Cyclosporine), Contracted as an External Consultant. Davie, A.: Other, Neoral (Cyclosporine), Employed as an External Consultant. Campbell, R.: Other, Neoral (Cyclosporine), Contracted as an External Consultant. Ricci, J.: Other, Neoral (Cyclosporine), Contracted as an External Consultant. Escrig, C.: Employee, Neoral (Cyclosporine). Gokhale, S.: Employee, Neoral (Cyclosporine). Lake, J.: Other, Neoral (Cyclosporine), Contracted as a Clinical Advisor.

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