The Role of Proteasome Inhibition With Bortezomib in the Treatment of Antibody-Mediated Rejection After Kidney-Only or Kidney-Combined Organ Transplantation

被引:92
作者
Flechner, Stuart M. [1 ]
Fatica, Richard [1 ]
Askar, Medhat [1 ]
Stephany, Brian R. [1 ]
Poggio, Emilio [1 ]
Koo, Anna [1 ]
Banning, Stacey [1 ]
Chiesa-Vottero, Andres [1 ]
Srinivas, Titte [1 ]
机构
[1] Cleveland Clin Fdn, Glickman Urol & Kidney Inst, Cleveland, OH 44195 USA
关键词
Antibody-mediated rejection; Bortezomib; Alloantibody; Complement; HLA ANTIBODIES; IN-VIVO; DESENSITIZATION; GLOMERULOPATHY; PROTEINURIA; RESPONSES;
D O I
10.1097/TP.0b013e3181fdd9b0
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. We report our initial experience in using the proteasome inhibitor, bortezomib, to treat established antibody-mediated rejection (AMR) in 20 patients. Methods. There were 16 kidney-only and 4 kidney-combined organ recipients with de novo donor-specific antibody (DSA) and histologic evidence of AMR with peritubular capillaries C4d deposition. AMR was diagnosed 19.8 months (range 1-71 months) posttransplant. Patients received intravenous corticosteroids followed by a 2-week cycle on days 1-4-8-11 of plasmapheresis and 1.3 mg/m(2) bortezomib; then 0.5 mg/kg intravenous immunoglobulin four times. Results. De novo class I DSA was detected in 11 (55%) and class II DSA in 18 (90%) recipients. The absolute mean difference between peak-nadir dominant DSA was 68,171 molecules of equivalent soluble fluorochrome (P<0.0001), representing 55%+/- 22%. Only two patients (10%) had undetectable DSA after treatment. Patient survival is 100%, and graft survival is 85% with a mean follow-up of 9.8 months (range 2-20 months). The treatment was generally well tolerated but caused fatigue, gastrointestinal complaints, fluid retention, and thrombocytopenia in a number of patients. The last follow-up estimated glomerular filtration rate was 41.9 +/- 16.8 mL/min (range 20.6-72.2 mL/min). However, only 25% returned to their baseline renal function before AMR, and many have proteinuria with urine protein/creatinine more than 0.5 in 41% and more than 1.0 in 18%. Conclusions. The bortezomib-containing regimen demonstrated activity in AMR but seems to be most effective before the onset of significant renal dysfunction (serum creatinine <3 mg/dL) or proteinuria (<1 g/day). The best use of bortezomib to treat AMR should be evaluated in controlled trials using dosing strategies that include longer courses or retreatment schedules.
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页码:1486 / 1492
页数:7
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