High intrapatient variability of tacrolimus exposure associated with poorer outcomes in liver transplantation
Dopazo, Cristina (Universitat Autònoma de Barcelona. Departament de Cirurgia)
Bilbao, Itxarone (Universitat Autònoma de Barcelona. Departament de Cirurgia)
García, Sonia (Hospital Universitari Vall d'Hebron)
Gómez Gavara, Concepción (Hospital Universitari Vall d'Hebron)
Caralt, Mireia (Hospital Universitari Vall d'Hebron)
Campos Varela, Isabel (Hospital Universitari Vall d'Hebron)
Castells, Lluís (Hospital Universitari Vall d'Hebron)
Hidalgo i Llompart, Ernest (Universitat Autònoma de Barcelona)
Moreso, Francisco (Hospital Universitari Vall d'Hebron)
Montoro, Bruno (Hospital Universitari Vall d'Hebron)
Charco, Ramon (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona. Departament de Medicina

Data:	2022
Resum:	Tacrolimus (TAC) is a dose-dependent immunosuppressor with considerable intrapatient variability (IPV) in its pharmacokinetics. The aim of this work is to ascertain the association between TAC IPV at 6 months after liver transplantation (LT) and patient outcome. This single-center cohort study retrospectively analyzed adult patients who underwent transplantation from 2015 to 2019 who survived the first 6 months with a functioning graft. The primary end point was the patient's probability of death and the secondary outcome was the loss of renal function between month 6 and the last follow-up. TAC IPV was estimated by calculating the coefficient of variation (CV) of the dose-corrected concentration (C/D) between the third and sixth months post-LT. Of the 140 patients who underwent LT included in the study, the low-variability group (C/D CV < 27%) comprised 105 patients and the high-variability group (C/D CV ≥ 27%) 35 patients. One-, 3-, and 5-year patient survival rates were 100%, 82%, and 72% in the high-variability group versus 100%, 97%, and 93% in the low-variability group, respectively (p = 0. 005). Moreover, significant impaired renal function was observed in the high-variability group at 1 year (69 ± 16 ml/min/1. 73 m 2 vs. 78 ± 16 ml/min/1. 73 m 2, p = 0. 004) and at 2 years post-LT (69 ± 17 ml/min/1. 73 m 2 vs. 77 ± 15 ml/min/1. 73 m 2, p = 0. 03). High C/D CV 3-6 months remained independently associated with worse survival (hazard ratio = 3. 57, 95% CI = 1. 32-9. 67, p = 0. 012) and loss of renal function (odds ratio = 3. 47, 95% CI = 1. 30-9. 20, p = 0. 01). Therefore, high IPV between the third and sixth months appears to be an early and independent predictor of patients with poorer liver transplant outcomes.
Ajuts:	Instituto de Salud Carlos III PI19/00330
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Clinical and Translational Science, Vol. 15, Num. 6 (june 2022) , p. 1544-1555, ISSN 1752-8062

DOI: 10.1111/cts.13276
PMID: 35373449

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