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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Nephrology, Hospital Clinic Barcelona, Barcelona, Spain.
Erika
E
De Sousa-Amorim
Nephrology, Hospital Clinic Barcelona, Barcelona, Spain.|Laboratori Experimental de Nefrologia i Trasplantament (LENIT), CRB CELLEX.
Ignacio
I
Revuelta
Nephrology, Hospital Clinic Barcelona, Barcelona, Spain.|Laboratori Experimental de Nefrologia i Trasplantament (LENIT), CRB CELLEX.
Fritz
F
Diekmann
Nephrology, Hospital Clinic Barcelona, Barcelona, Spain.
Frederic
F
Cofan
Hemotherapy and Hemostasis, Hospital Clinic Barcelona, Barcelona, Spain.
Miquel
M
Lozano
Hemotherapy and Hemostasis, Hospital Clinic Barcelona, Barcelona, Spain.
Joan
J
Cid
Immunology, Hospital Clinic Barcelona, Barcelona, Spain.
Eduard
E
Palou
Histopathology, Hospital Clinic Barcelona, Barcelona, Spain.
Manel
M
Sole
Nephrology, Hospital Clinic Barcelona, Barcelona, Spain.|Laboratori Experimental de Nefrologia i Trasplantament (LENIT), CRB CELLEX.
Josep María
JM
Campistol
Nephrology, Hospital Clinic Barcelona, Barcelona, Spain.|Laboratori Experimental de Nefrologia i Trasplantament (LENIT), CRB CELLEX.
Federic
F
Oppenheimer
D000208:Acute Disease; D061605:Administration, Intravenous; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D000069286:Bortezomib / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D061988:Proteasome Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D020127:Recovery of Function; D006435:Renal Dialysis; D012189:Retrospective Studies; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D061988:Proteasome Inhibitors; D000069286:Bortezomib
acute humoral rejection; bortezomib; kidney transplantation; proteasome inhibitor; treatment