MO1009: Early Switch from Fast IR-TAC Metabolizers to LCP-TAC Improves Renal Allograft Function

Abstract

BACKGROUND AND AIMS In contrast to slow tacrolimus (Tac) metabolism, fast metabolism is associated with a more rapid decline in renal function [1–3]. Because the pharmacokinetics of LCP-Tac (LCPT) differ from those of immediate-release Tac (IR-Tac), we hypothesized that the estimated glomerular filtration rate (eGFR) of fast metabolizers, in particular, would be improved by switching from IR-Tac to LCPT. METHOD We included renal allograft recipients receiving a de novo immunosuppression with IR-Tac, mycophenolate and prednisolone. A Tac concentration-to-dose ratio (C/D ratio, surrogate for bioavailability) <1.05 ng/mL*1/mg defined fast metabolizers and ≥ 1.05 ng/mL*1/mg slow metabolizers one months after renal transplantation (RTx). All patients were switched to LCPT 1 month after transplantation or later. During a 3-year follow-up, Tac doses, C/D ratios, eGFR, infection and rejection rates were compared between the metabolizer groups. RESULTS Fast metabolizers (n = 58) were switched to LCPT earlier than slow metabolizers (n = 22) after RTx (2.0 (1.0–253.1 versus 13.2 (1.2–172.8 months, P = .005). Tac doses were decreased by ∼65% in both groups after 12 months of conversion to LCPT. C/D ratios at 12 months increased from 0.66 (0.24–2.10) to 1.74 (0.42–5.43) (+163%) in fast and from 1.15 (0.32–3.60) to 2.75 (1.08–5.90) (+139%) in slow metabolizers. Fast metabolizers showed significant recovery of mean eGFR as early as one month after conversion (48.5 ± 17.6 versus 41.5 ± 17.0 mL/min/1.73 m²; P = .032) and at all subsequent time points. Conversion to LCPT did not result in relevant eGFR changes in slow metabolizers. Infection and rejection rates were low and did not differ between the groups before and after conversion. CONCLUSION Switching to LCPT increases the Tac bioavailability. This was associated with a significant recovery of renal function in fast metabolizers. Conversion to LCPT is safe and beneficial early after RTx.