Improved Kidney Allograft Function after Early Conversion of Fast IR-Tac Metabolizers to LCP-Tac

Fast tacrolimus (Tac) metabolism is associated with a more rapid decline of renal function after renal transplantation (RTx). Because the pharmacokinetics of LCP-Tac (LCPT) and immediate-release Tac (IR-Tac) differ, we hypothesized that switching from IR-Tac to LCPT in kidney transplant recipients would improve the estimated glomerular filtration rate (eGFR), particularly in fast metabolizers. For proof of concept, we performed a pilot study including RTx patients who received de novo immunosuppression with IR-Tac. A Tac concentration-to-dose ratio (C/D ratio) < 1.05 ng/mL center dot 1/mg defined fast metabolizers and >= 1.05 ng/mL center dot 1/mg slow metabolizers one month after RTx. Patients were switched to LCPT >= 1 month after transplantation and followed for 3 years. Fast metabolizers (n = 58) were switched to LCPT earlier than slow metabolizers (n = 22) after RTx (2.0 (1.0-253.1) vs. 13.2 (1.2-172.8) months, p = 0.005). Twelve months after the conversion to LCPT, Tac doses were reduced by about 65% in both groups. The C/D ratios at 12 months had increased from 0.66 (0.24-2.10) to 1.74 (0.42-5.43) in fast and from 1.15 (0.32-3.60) to 2.75 (1.08-5.90) in slow metabolizers. Fast metabolizers showed noticeable recovery of mean eGFR already one month after the conversion (48.5 +/- 17.6 vs. 41.5 +/- 17.0 mL/min/1.73 m(2), p = 0.032) and at all subsequent time points, whereas the eGFR in slow metabolizers remained stable. Switching to LCPT increased Tac bioavailability, C/D ratio, and was associated with a noticeable recovery of renal function in fast metabolizers. Conversion to LCPT is safe and beneficial early after RTx.

Automated summary

A switch from immediate-release tacrolimus (IR-Tac) to extended-release tacrolimus (LCPT) can improve renal function in kidney transplant recipients, particularly in fast metabolizers.