Published in:
Journal of Clinical Medicine, 11 (2022) 5, Seite 1290
Language:
English
DOI:
10.3390/jcm11051290
ISSN:
2077-0383
Origination:
Footnote:
Description:
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·1/mg defined fast metabolizers and ≥1.05 ng/mL·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 m², 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.