Factors Predicting Risk for Antibody-mediated Rejection and Graft Loss in Highly Human Leukocyte Antigen Sensitized Patients Transplanted After Desensitization. Issue 7 (July 2015)

• Record Type: Journal Article
• Authors: Vo, Ashley A.; Sinha, Aditi; Haas, Mark; Choi, Jua; Mirocha, James; Kahwaji, Joseph; Peng, Alice; Villicana, Rafael; Jordan, Stanley C.
• Is Part Of: Transplantation. Volume 99:Issue 7(2015)
• Publication Date: 2015-07
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000000525
• Languages: English
• ISSNs: 0041-1337

Abstract

Abstract : Background: Desensitization with intravenous immunoglobulin and rituximab (I+R) significantly improves transplant rates in highly sensitized patients, but antibody-mediated rejection (ABMR) remains a concern. Patients and Methods: Between July 2006 and December 2012, 226 highly sensitized patients received transplants after desensitization. Most received alemtuzumab induction and standard immunosuppression. Two groups were examined: ABMR − (n = 181) and ABMR + (n = 45, 20%). Risk factors for ABMR, pathology, and outcomes were assessed. Results: Significant risks for ABMR included previous transplants and pregnancies as sensitizing events, donor-specific antibody (DSA) relative intensity scores greater than 17, presence of both class I and II DSAs at transplant and time on waitlist. The ABMR − showed a significant benefit for graft survival and glomerular filtration rate at 5 years ( P < 0.0001). Banff pathology characteristics for ABMR + patients with or without graft loss did not differ. C4d + versus C4d − ABMR did not predict graft loss ( P = 0.086). Thrombotic microangiopathy (TMA + ) significantly predicted graft failure ( P = 0.045). The ABMR episodes were treated with I+R (n = 25), or, in more severe ABMR +, plasma exchange (PLEX)+I+R (n = 20). Graft survival for patients treated with I+R was superior ( P = 0.028). Increased mortality was seen in ABMR + patients experiencing graft loss after ABMR treatment ( P = 0.004). The PLEX + Eculizumab improved graft survival for TMA + patients ( P = 0.036). Conclusion: Patients desensitized with I+R who remain ABMR − have long-term graft and patient survival. The ABMR + patients have significantly reduced graft survival and glomerular filtration rate at 5 years, especially TMA + . Severe ABMR + episodes benefit from treatment with PLEX + Eculizumab. The DSA-relative intensity scores at transplant was a strong predictor of ABMR. Donor-specific antibody avoidance and reduction strategies before transplantation are critical to avoiding ABMR and improving long-term outcomes. Abstract : A single-center retrospective study of desensitized renal allograft recipients shows that if antibody-mediated rejection (AMR) does not occur then graft survival is excellent. AMR can be successfully treated with plasmaphorses, intravenous immunoglobulin, anti-CD20, and eculizumab, although avoidance of high titred donor-specific antibodies remains the most effective measure.