title: Factors Predicting Risk for Antibody-mediated Rejection and Graft Loss in Highly Human Leukocyte Antigen Sensitized Patients Transplanted After Desensitization.
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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1 Kidney Transplant Program and Transplant Immunology, Cedars-Sinai Medical Center, Los Angeles, CA. 2 Division of Pediatric Nephrology, All India Institute of Medical Sciences, New Delhi, India. 3 Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA. 4 Biostatistics Core, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Vo
authors.forename: Aditi
authors.initials: A
authors.lastname: Sinha
authors.forename: Mark
authors.initials: M
authors.lastname: Haas
authors.forename: Jua
authors.initials: J
authors.lastname: Choi
authors.forename: James
authors.initials: J
authors.lastname: Mirocha
authors.forename: Joseph
authors.initials: J
authors.lastname: Kahwaji
authors.forename: Alice
authors.initials: A
authors.lastname: Peng
authors.forename: Rafael
authors.initials: R
authors.lastname: Villicana
authors.forename: Stanley C
authors.initials: SC
authors.lastname: Jordan
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003888:Desensitization, Immunologic / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects*; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007518:Isoantibodies / Q000097:blood*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D000069283:Rituximab / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D000069283:Rituximab