Conversion from Standard-Release Tacrolimus to MeltDose® Tacrolimus (LCPT) Improves Renal Function after Liver Transplantation

Abstract

Renal impairment is a typical side effect of tacrolimus (Tac) treatment in liver transplant (LT) recipients. One strategy to avoid renal dysfunction is to increase the concentration/dose (C/D) ratio by improving drug bioavailability. LT recipients converted from standard-release Tac to MeltDose^® Tac (LCPT), a novel technological formulation, were able to reduce the required Tac dose due to higher bioavailability. Hence, we hypothesize that such a conversion increases the C/D ratio, resulting in a preservation of renal function. In the intervention group, patients were switched from standard-release Tac to LCPT. Clinical data were collected for 12 months after conversion. Patients maintained on standard-release Tac were enrolled as a control group. Twelve months after conversion to LCPT, median C/D ratio had increased significantly by 50% (p < 0.001), with the first significant increase seen 3 months after conversion (p = 0.008). In contrast, C/D ratio in the control group was unchanged after 12 months (1.75 vs. 1.76; p = 0.847). Estimated glomerular filtration rate (eGFR) had already significantly deteriorated in the control group at 9 months (65.6 vs. 70.6 mL/min/1.73 m² at study onset; p = 0.006). Notably, patients converted to LCPT already had significant recovery of mean eGFR 6 months after conversion (67.5 vs. 65.3 mL/min/1.73 m² at study onset; p = 0.029). In summary, conversion of LT recipients to LCPT increased C/D ratio associated with renal function improvement.

Keywords: C/D ratio; LCPT; MeltDose®; liver transplantation; metabolism; renal function; tacrolimus.

Figure 1

Study design and patient enrolment. A total of 164 liver transplant (LT) recipients were screened for eligibility. Only LT recipients who were started on IR- or ER-Tac (standard-release tacrolimus) and continued taking this drug until the beginning of the study were included. During the enrolment period (March 2017–August 2018), 121 patients met the inclusion criteria and were either switched to LCPT (once-daily MeltDose^® tacrolimus (Tac); intervention group) or maintained on standard-release tacrolimus (control group). Clinical data were analysed in a 12-month follow-up. We hypothesized that conversion from standard-release Tac to LCPT increases concentration/dose (C/D) ratio and thereby preserves renal function

Figure 2

Boxplots of C/D ratio among patients receiving LCPT (dark grey) or standard-release Tac (light brown) at baseline and 3, 6, 9 and 12 months later. There were significant differences between the two study groups at 6 and 12 months after conversion. p-values reflect differences between the groups at each time point.

Figure 3

Glomerular filtration rate (eGFR; mL/min/1.73 m²) over time and the difference from baseline at each time point (ΔeGFR ± SEM) in each study group. Improved renal function with a significantly increased mean ΔeGFR was already observed 3 months after conversion to LCPT (dark grey). p-values reflect comparison of ΔeGFR between the study groups.