AUTHOR=Piñeiro Gaston J. , Montagud-Marrahi Enrique , Ríos José , Ventura-Aguiar Pedro , Cucchiari David , Revuelta Ignacio , Lozano Miquel , Cid Joan , Cofan Frederic , Esforzado Nuria , Palou Eduard , Oppenheimer Federico , Campistol Josep M. , Bayés-Genís Beatriu , Rovira Jordi , Diekmann Fritz 

TITLE=Influence of Persistent Inflammation in Follow-Up Biopsies After Antibody-Mediated Rejection in Kidney Transplantation

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.761919

DOI=10.3389/fmed.2021.761919

ISSN=2296-858X

ABSTRACT=<p><bold>Background:</bold> Despite recent advances in immunosuppression treatment, antibody-mediated rejection (ABMR) remains the leading cause of kidney graft loss. Information about prognostic markers and the efficacy of treatment is scarce.</p><p><bold>Methods:</bold> Retrospective study with kidney recipients diagnosed an active ABMR from January 1, 2004 to December 31, 2019 to explore the influence of persistent inflammation in follow-up biopsies on graft survival after ABMR treatment.</p><p><bold>Results:</bold> About 116 patients were included. Active ABMR were treated with a combination of plasma exchange (PE), intravenous immunoglobulin (IVIg), rituximab, and steroids. At 6 months of treatment, 63 (54.3%) patients presented a stabilization or improvement in kidney-graft function. The effectiveness varied depending on the timepoint of the presentation between transplantation and rejection, which is lower for those with late ABMR (63 vs. 21% for early vs. late ABMR, respectively). Ninety patients (77%) underwent a control biopsy after ABMR treatment, from which 46 (51%) responded to the treatment. Microvascular inflammation (MVI) persisted in 64 (71%) biopsies, whereas tubulitis persisted in 17 (19%) biopsies. Death-censored graft survival at 1 year was significantly lower in patients with persistent MVI (86% vs. 95% without persistent MVI, <italic>P</italic> = 0.002), or with persistent tubulitis (44% vs. 66% without tubulitis, <italic>P</italic> = 0.02). In the Cox Regression analysis, the persistence of MVI [hazard ratio (HR), 4.50 (95%CI, 1.35–14.96), <italic>P</italic> = 0.01] and tubulitis [HR 2.88 95%CI (1.24–6.69), <italic>P</italic> = 0.01) in follow-up biopsies significantly increased the risk of graft failure.</p><p><bold>Conclusion:</bold> Persistent inflammation in follow-up biopsies after ABMR treatment was associated with an increased risk of graft loss, even without meeting Banff rejection criteria.</p><p><bold>Study Registration:</bold> Agencia Española de Medicamentos y Productos Sanitarios (AEMPS): 14566/RG 24161. Study code: UTRINM-2017-01.</p>