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Factors Predicting Risk for Antibody-mediated Rejection and Graft Loss in Highly Human Leukocyte Antigen Sensitized Patients Transplanted After Desensitization
- Source :
- Transplantation. 99(7)
- Publication Year :
- 2015
-
Abstract
- Desensitization with intravenous immunoglobulin and rituximab (I+R) significantly improves transplant rates in highly sensitized patients, but antibody-mediated rejection (ABMR) remains a concern.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.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 (P0.0001). 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).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.
- Subjects :
- Adult
Graft Rejection
Male
medicine.medical_specialty
Pathology
Thrombotic microangiopathy
Time Factors
Urology
Renal function
Human leukocyte antigen
Kaplan-Meier Estimate
HLA Antigens
Isoantibodies
Predictive Value of Tests
Risk Factors
Medicine
Humans
Retrospective Studies
Transplantation
biology
business.industry
Histocompatibility Testing
Graft Survival
Immunoglobulins, Intravenous
Eculizumab
Middle Aged
medicine.disease
Kidney Transplantation
Histocompatibility
Immunity, Humoral
Treatment Outcome
Desensitization, Immunologic
Predictive value of tests
biology.protein
Female
Antibody
business
Rituximab
Biomarkers
Immunosuppressive Agents
medicine.drug
Subjects
Details
- ISSN :
- 15346080
- Volume :
- 99
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Transplantation
- Accession number :
- edsair.doi.dedup.....11a273ef143e15d8f238e507afe52651