Progression of Interstitial Fibrosis and Tubular Atrophy in Low Immunological Risk Renal Transplants Monitored by Sequential Surveillance Biopsies : The Influence of TAC Exposure and Metabolism
Chamoun, Betty (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Torres, Irina B. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Gabaldón, Alejandra (Hospital Universitari Vall d'Hebron)
Sellarés Nadal, Joana (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Perelló, Manel (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Castellà Fernández, Eva (Hospital Universitari Vall d'Hebron)
Guri, Xavier (Hospital Universitari Vall d'Hebron)
Salcedo, Maite (Hospital Universitari Vall d'Hebron)
Toapanta, Néstor (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Cidraque, Ignacio (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Moreso, Francesc (Universitat Autònoma de Barcelona. Departament de Medicina)
Seron, Daniel (Universitat Autònoma de Barcelona. Departament de Medicina)

Data:	2021
Resum:	The combination of tacrolimus (TAC) and mycophenolate is the most widely employed maintenance immunosuppression in renal transplants. Different surrogates of tacrolimus exposure or metabolism such as tacrolimus trough levels (TAC-C), coefficient of variation of tacrolimus (CV-TAC-C), time in therapeutic range (TTR), and tacrolimus concentration dose ratio (C/D) have been associated with graft outcomes. We explore in a cohort of low immunological risk renal transplants (n = 85) treated with TAC, mycophenolate mofetil (MMF), and steroids and then monitored by paired surveillance biopsies the association between histological lesions and TAC-C at the time of biopsy as well as CV-TAC-C, TTR, and C/D during follow up. Interstitial inflammation (i-Banff score ≥ 1) in the first surveillance biopsy was associated with TAC-C (odds ratio (OR): 0. 69, 95% confidence interval (CI): 0. 50-0. 96; p = 0. 027). In the second surveillance biopsy, inflammation was associated with time below the therapeutic range (OR: 1. 05 and 95% CI: 1. 01-1. 10; p = 0. 023). Interstitial inflammation in scarred areas (i-IFTA score ≥ 1) was not associated with surrogates of TAC exposure/metabolism. Progression of interstitial fibrosis/tubular atrophy (IF/TA) was observed in 35 cases (41. 2%). Multivariate regression logistic analysis showed that mean C/D (OR: 0. 48; 95% CI: 0. 25-0. 92; p = 0. 026) and IF/TA in the first biopsy (OR: 0. 43, 95% CI: 0. 24-0. 77, p = 0. 005) were associated with IF/TA progression between biopsies. A low C/D ratio is associated with IF/TA progression, suggesting that TAC nephrotoxicity may contribute to fibrosis progression in well immunosuppressed patients. Our data support that TAC exposure is associated with inflammation in healthy kidney areas but not in scarred tissue.
Ajuts:	Instituto de Salud Carlos III PI 18/01704 Instituto de Salud Carlos III PI 18/01382 Ministerio de Economía y Competitividad RD16/0009/0030
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, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglè
Document:	Article ; recerca ; Versió publicada
Matèria:	Tacrolimus ; Renal transplantation ; Protocol biopsies ; Concentration dose ratio ; Time in therapeutic range ; Coefficient of variation
Publicat a:	Journal of clinical medicine, Vol. 10 (january 2021) , ISSN 2077-0383

DOI: 10.3390/jcm10010141
PMID: 33406589

14 p, 1.0 MB

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