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

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

doi:10.3389/fmed.2021.761919

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

Front Med (Lausanne). 2021 Nov 12:8:761919. doi: 10.3389/fmed.2021.761919. eCollection 2021.

Authors

Gaston J Piñeiro^{1

2}, Enrique Montagud-Marrahi^{1

2}, José Ríos³, Pedro Ventura-Aguiar^{1

2}, David Cucchiari^{1

2}, Ignacio Revuelta^{1

2}, Miquel Lozano⁴, Joan Cid⁴, Frederic Cofan¹, Nuria Esforzado¹, Eduard Palou⁵, Federico Oppenheimer^{1

2}, Josep M Campistol^{1

2

6}, Beatriu Bayés-Genís^{1

2}, Jordi Rovira^{2

6}, Fritz Diekmann^{1

2

6}

Affiliations

¹ Department of Nephrology and Kidney Transplantation, Hospital Clinic Barcelona, Barcelona, Spain.
² Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
³ Medical Statistics Platform, Institut d'Investigacions Biomques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
⁴ Apheresis Unit, Department of Hemotherapy and Hemostasis, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain.
⁵ Department of Immunology, Hospital Clc de Barcelona, Universitat de Barcelona, Barcelona, Spain.
⁶ Red de Investigación Renal (REDINREN), Madrid, Spain.

Abstract

Background: 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. Methods: 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. Results: 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, P = 0.002), or with persistent tubulitis (44% vs. 66% without tubulitis, P = 0.02). In the Cox Regression analysis, the persistence of MVI [hazard ratio (HR), 4.50 (95%CI, 1.35-14.96), P = 0.01] and tubulitis [HR 2.88 95%CI (1.24-6.69), P = 0.01) in follow-up biopsies significantly increased the risk of graft failure. Conclusion: Persistent inflammation in follow-up biopsies after ABMR treatment was associated with an increased risk of graft loss, even without meeting Banff rejection criteria. Study Registration: Agencia Española de Medicamentos y Productos Sanitarios (AEMPS): 14566/RG 24161. Study code: UTRINM-2017-01.

Keywords: antibody-mediated rejection; follow-up biopsy; graft failure; kidney transplantation; microvascular inflammation.