1. 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
- Author
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Néstor Toapanta, Irina B. Torres, Manel Perelló, Francesc Moreso, Ignacio Cidraque, Joana Sellarés, Betty Chamoun, Eva Castellà, Alejandra Gabaldon, Maite Salcedo, Xavier Guri, Daniel Serón, Institut Català de la Salut, [Chamoun B, Torres IB, Sellarés J, Perelló M, Toapanta NG, Cidraque I] Servei de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Gabaldón A, Salcedo M] Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Castellá E, Guri X] Servei de Radiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Moreso F, Seron D] Servei de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
medicine.medical_treatment ,030232 urology & nephrology ,lcsh:Medicine ,030230 surgery ,Gastroenterology ,0302 clinical medicine ,Fibrosis ,Therapeutics::Renal Replacement Therapy::Kidney Transplantation [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,tacrolimus ,Kidney ,Concentration dose ratio ,medicine.diagnostic_test ,Ronyons - Trasplantació ,enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales::nefritis::nefritis intersticial [ENFERMEDADES] ,Immunosuppression ,General Medicine ,Ronyons - Malalties ,renal transplantation ,Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Immunologic Factors::Immunosuppressive Agents [CHEMICALS AND DRUGS] ,surgical procedures, operative ,protocol biopsies ,medicine.anatomical_structure ,time in therapeutic range ,concentration dose ratio ,medicine.medical_specialty ,Coefficient of variation ,Tubular atrophy ,chemical and pharmacologic phenomena ,Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Nephritis::Nephritis, Interstitial [DISEASES] ,Article ,Tacrolimus ,Nephrotoxicity ,03 medical and health sciences ,stomatognathic system ,Internal medicine ,Biopsy ,Protocol biopsies ,medicine ,Time in therapeutic range ,business.industry ,lcsh:R ,Renal transplantation ,Odds ratio ,terapéutica::tratamiento de reemplazo renal::trasplante de riñón [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,medicine.disease ,coefficient of variation ,stomatognathic diseases ,Medicaments immunosupressors ,business ,acciones y usos químicos::acciones farmacológicas::efectos fisiológicos de los fármacos::factores inmunitarios::inmunosupresores [COMPUESTOS QUÍMICOS Y DROGAS] - Abstract
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-C0), coefficient of variation of tacrolimus (CV-TAC-C0), 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-C0 at the time of biopsy as well as CV-TAC-C0, TTR, and C/D during follow up. Interstitial inflammation (i-Banff score &ge, 1) in the first surveillance biopsy was associated with TAC-C0 (odds ratio (OR): 0.69, 95% confidence interval (CI): 0.50&ndash, 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&ndash, 1.10, p = 0.023). Interstitial inflammation in scarred areas (i-IFTA score &ge, 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&ndash, 0.92, p = 0.026) and IF/TA in the first biopsy (OR: 0.43, 95% CI: 0.24&ndash, 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.
- Published
- 2021