Clinical Relevance of Corticosteroid Withdrawal on Graft Histological Lesions in Low-Immunological-Risk Kidney Transplant Patients

Domingo Hernández, Juana Alonso-Titos, Teresa Vázquez, Myriam León, Abelardo Caballero, María Angeles Cobo, Eugenia Sola, Verónica López, Pedro Ruiz-Esteban, Josep María Cruzado, Joana Sellarés, Francesc Moreso, Anna Manonelles, Alberto Torío, Mercedes Cabello, Juan Delgado-Burgos, Cristina Casas, Elena Gutiérrez, Cristina Jironda, Julia Kanter, Daniel Serón, Armando Torres, Domingo Hernández, Juana Alonso-Titos, Teresa Vázquez, Myriam León, Abelardo Caballero, María Angeles Cobo, Eugenia Sola, Verónica López, Pedro Ruiz-Esteban, Josep María Cruzado, Joana Sellarés, Francesc Moreso, Anna Manonelles, Alberto Torío, Mercedes Cabello, Juan Delgado-Burgos, Cristina Casas, Elena Gutiérrez, Cristina Jironda, Julia Kanter, Daniel Serón, Armando Torres

Abstract

The impact of corticosteroid withdrawal on medium-term graft histological changes in kidney transplant (KT) recipients under standard immunosuppression is uncertain. As part of an open-label, multicenter, prospective, phase IV, 24-month clinical trial (ClinicalTrials.gov, NCT02284464) in low-immunological-risk KT recipients, 105 patients were randomized, after a protocol-biopsy at 3 months, to corticosteroid continuation (CSC, n = 52) or corticosteroid withdrawal (CSW, n = 53). Both groups received tacrolimus and MMF and had another protocol-biopsy at 24 months. The acute rejection rate, including subclinical inflammation (SCI), was comparable between groups (21.2 vs. 24.5%). No patients developed dnDSA. Inflammatory and chronicity scores increased from 3 to 24 months in patients with, at baseline, no inflammation (NI) or SCI, regardless of treatment. CSW patients with SCI at 3 months had a significantly increased chronicity score at 24 months. HbA1c levels were lower in CSW patients (6.4 ± 1.2 vs. 5.7 ± 0.6%; p = 0.013) at 24 months, as was systolic blood pressure (134.2 ± 14.9 vs. 125.7 ± 15.3 mmHg; p = 0.016). Allograft function was comparable between groups and no patients died or lost their graft. An increase in chronicity scores at 2-years post-transplantation was observed in low-immunological-risk KT recipients with initial NI or SCI, but CSW may accelerate chronicity changes, especially in patients with early SCI. This strategy did, however, improve the cardiovascular profiles of patients.

Keywords: borderline lesions; chronic graft histological changes; corticosteroids withdrawal; kidney transplant; low immunological risk; protocol biopsy; rejection; subclinical inflammation.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Study design timeline.
Figure 2
Figure 2
Evolution of histological data from 3 to 24 months. Patients with acute inflammation at 3- and 24-months post-transplantation with (A) NI and (B) SCI. i, interstitial; t, tubulitis.
Figure 3
Figure 3
Changes in chronicity scores from 3 to 24 months in both study groups in patients with SCI at the 3-month protocol biopsy, excluding patients with isolated mild inflammation without tubulitis (i1, t0) (n = 22).

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