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Bortezomib for refractory acute antibody-mediated rejection in kidney transplant recipients: A single-centre case series

Authors :
Erika, De Sousa-Amorim
Ignacio, Revuelta
Fritz, Diekmann
Frederic, Cofan
Miquel, Lozano
Joan, Cid
Eduard, Palou
Manel, Sole
Josep María, Campistol
Federic, Oppenheimer
Source :
Nephrology (Carlton, Vic.). 21(8)
Publication Year :
2015

Abstract

Acute antibody-mediated rejection (ABMR) after kidney transplantation (KT) is associated with poor allograft survival. Current therapies for ABMR are able to deplete B-lymphocytes but do not target plasma cells. Bortezomib is a proteasome inhibitor that can eliminate plasma cells and has demonstrated utility in the treatment of ABMR.A retrospective study was carried out from 2010 to 2014, including all patients with ABMR refractory to conventional treatment who received bortezomib. Bortezomib (1.3 mg/m(2) ) was administered intravenously on days 1, 4, 8, and 11. Renal function, graft survival, follow-up biopsies, and donor-specific antibodies (DSA) were recorded.We identified seven patients. Of these, high immunological risk was found in 6 of 7, preformed DSA were found in 5 of 7, flow cytometry crossmatch was positive in 4 of 7, and desensitization before KTx was provided in 6 of 7 patients. ABMR was diagnosed at a median of 90 days (8-167) post-KT. After bortezomib therapy, renal function improved or stabilized in 5 of 7 patients and progressively deteriorated in 2 of 7, leading to haemodialysis after 7 and 11 months, respectively. Follow-up kidney biopsies showed persistence of ABMR in 2 of 7, chronic active ABMR 3 of 7 and inactive chronic lesions in 2 of 7. DSA titres significantly decreased after treatment (P = 0.028). All patients experienced mild adverse events. After a follow-up of 22 ± 18 months, three grafts were lost (42%) and four remained functioning.Bortezomib could be useful as an adjuvant therapy for ABMR refractory to conventional treatment with acceptable mid-term outcomes in these severe cases. More research is needed to develop strategies to better preserve graft function after refractory ABMR.

Details

ISSN :
14401797
Volume :
21
Issue :
8
Database :
OpenAIRE
Journal :
Nephrology (Carlton, Vic.)
Accession number :
edsair.pmid..........9d8a913fed60b846f76b8fd1505f1bca