Evolution of humoral lesions on follow-up biopsy stratifies the risk for renal graft loss after antibody-mediated rejection treatment.


Journal

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
ISSN: 1460-2385
Titre abrégé: Nephrol Dial Transplant
Pays: England
ID NLM: 8706402

Informations de publication

Date de publication:
23 11 2022
Historique:
received: 14 07 2021
pubmed: 9 6 2022
medline: 25 11 2022
entrez: 8 6 2022
Statut: ppublish

Résumé

The standard-of-care protocol, based on plasma exchanges, high-dose intravenous immunoglobulin and optimization of maintenance immunosuppression, can slow down the evolution of antibody-mediated rejection (AMR), but with high interindividual variability. Identification of a reliable predictive tool of the response to AMR treatment is a mandatory step for personalization of the follow-up strategy and to guide second-line therapies. Interrogation of the electronic databases of 2 French university hospitals (Lyon and Strasbourg) retrospectively identified 81 renal transplant recipients diagnosed with AMR without chronic lesions (cg score ≤1) at diagnosis and for whom a follow-up biopsy had been performed 3-6 months after initiation of therapy. The evolution of humoral lesions on follow-up biopsy (disappearance versus persistence versus progression) correlated with the risk for allograft loss (logrank test, P = .001). Patients with disappearance of humoral lesions had ∼80% graft survival at 10 years. The hazard ratio for graft loss in multivariate analysis was 3.91 (P = .04) and 5.15 (P = .02) for patients with persistence and progression of lesions, respectively. The non-invasive parameters classically used to follow the intensity of humoral alloimmune response (evolution of immunodominant DSA mean fluorescence intensity) and the decline of renal graft function (estimated glomerular filtration rate decrease and persistent proteinuria) showed little clinical value to predict the histological response to AMR therapy. We conclude that invasive monitoring of the evolution of humoral lesions by the mean of follow-up biopsy performed 3-6 months after the initiation of therapy is an interesting tool to predict long-term outcome after AMR treatment.

Sections du résumé

BACKGROUND
The standard-of-care protocol, based on plasma exchanges, high-dose intravenous immunoglobulin and optimization of maintenance immunosuppression, can slow down the evolution of antibody-mediated rejection (AMR), but with high interindividual variability. Identification of a reliable predictive tool of the response to AMR treatment is a mandatory step for personalization of the follow-up strategy and to guide second-line therapies.
METHODS
Interrogation of the electronic databases of 2 French university hospitals (Lyon and Strasbourg) retrospectively identified 81 renal transplant recipients diagnosed with AMR without chronic lesions (cg score ≤1) at diagnosis and for whom a follow-up biopsy had been performed 3-6 months after initiation of therapy.
RESULTS
The evolution of humoral lesions on follow-up biopsy (disappearance versus persistence versus progression) correlated with the risk for allograft loss (logrank test, P = .001). Patients with disappearance of humoral lesions had ∼80% graft survival at 10 years. The hazard ratio for graft loss in multivariate analysis was 3.91 (P = .04) and 5.15 (P = .02) for patients with persistence and progression of lesions, respectively. The non-invasive parameters classically used to follow the intensity of humoral alloimmune response (evolution of immunodominant DSA mean fluorescence intensity) and the decline of renal graft function (estimated glomerular filtration rate decrease and persistent proteinuria) showed little clinical value to predict the histological response to AMR therapy.
CONCLUSION
We conclude that invasive monitoring of the evolution of humoral lesions by the mean of follow-up biopsy performed 3-6 months after the initiation of therapy is an interesting tool to predict long-term outcome after AMR treatment.

Identifiants

pubmed: 35675302
pii: 6604385
doi: 10.1093/ndt/gfac192
doi:

Substances chimiques

Antibodies 0
Isoantibodies 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2555-2568

Informations de copyright

© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.

Auteurs

Antonin Bouchet (A)

Service de Transplantation, Néphrologie et Immunologie Clinique, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
Unité de Formation et de Recherche de Médecine Lyon Est, Université Claude-Bernard Lyon I, Lyon, France.

Brieuc Muller (B)

Service de Néphrologie et Transplantation, Les Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Jerome Olagne (J)

Service de Néphrologie et Transplantation, Les Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Thomas Barba (T)

Unité de Formation et de Recherche de Médecine Lyon Est, Université Claude-Bernard Lyon I, Lyon, France.
Institut National de la Santé et de la Recherche Médicale U1111, Lyon, France.

Mélanie Joly (M)

Service de Néphrologie et Transplantation, Les Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Augustin Obrecht (A)

Service de Néphrologie et Transplantation, Les Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Maud Rabeyrin (M)

Institut de Pathologie Multisite, Groupement Hospitalier Est, Bron, France.

Frédérique Dijoud (F)

Institut de Pathologie Multisite, Groupement Hospitalier Est, Bron, France.

Cécile Picard (C)

Institut de Pathologie Multisite, Groupement Hospitalier Est, Bron, France.

Sarah Mezaache (S)

Service de Transplantation, Néphrologie et Immunologie Clinique, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
Unité de Formation et de Recherche de Médecine Lyon Est, Université Claude-Bernard Lyon I, Lyon, France.

Antoine Sicard (A)

Service de Transplantation, Néphrologie et Immunologie Clinique, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
Unité de Formation et de Recherche de Médecine Lyon Est, Université Claude-Bernard Lyon I, Lyon, France.

Alice Koenig (A)

Service de Transplantation, Néphrologie et Immunologie Clinique, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
Unité de Formation et de Recherche de Médecine Lyon Est, Université Claude-Bernard Lyon I, Lyon, France.
Institut National de la Santé et de la Recherche Médicale U1111, Lyon, France.

Anne Parissiadis (A)

Laboratoire d'Histocompatibilité, Etablissement Français du Sang, Strasbourg, France.

Valérie Dubois (V)

Institut National de la Santé et de la Recherche Médicale U1111, Lyon, France.
Laboratoire d'Histocompatibilité, Etablissement Français du Sang, Lyon, France.

Emmanuel Morelon (E)

Service de Transplantation, Néphrologie et Immunologie Clinique, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
Unité de Formation et de Recherche de Médecine Lyon Est, Université Claude-Bernard Lyon I, Lyon, France.
Institut National de la Santé et de la Recherche Médicale U1111, Lyon, France.

Sophie Caillard (S)

Service de Néphrologie et Transplantation, Les Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Olivier Thaunat (O)

Service de Transplantation, Néphrologie et Immunologie Clinique, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
Unité de Formation et de Recherche de Médecine Lyon Est, Université Claude-Bernard Lyon I, Lyon, France.
Institut National de la Santé et de la Recherche Médicale U1111, Lyon, France.

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