Clinical Outcomes of Antibody-Mediated Rejection with or without Anti-human Leukocyte Antigen (HLA) Donor-Specific Antibody

Background: Antibody-mediated rejection (ABMR) is a major cause of late kidney allograft loss. It is increasingly recognized that histologic ABMRs without detectable donor-specific antibodies (DSA) can occur. Several studies have examined the prognosis of DSA-negative ABMR; however, there remains a need for further evidence. Methods: From a single-center, retrospective study conducted from 2006 to 2021, 2,498 kidney transplant patients were screened, and 1,483 were available for at least one renal biopsy. Of these, 290 patients with biopsy-proven T-cell mediated rejection (TCMR) or ABMR were included in the study. The patients were categorized into TCMR, DSA-positive ABMR, and DSA-negative ABMR groups. DSAs were measured between the six months before and after the biopsies. The primary outcome was death-censored graft failure, and the secondary outcome was death-uncensored graft failure. Results: The incidences for death-censored graft failure of TCMR, DSA-positive ABMR, and DSA-negative ABMR were 4.56, 4.98, and 6.23 per 100 patient-years. Over a median follow-up period of 5 years, death-censored graft failure occurred in 94 (32.4%) patients, with an incidence of 5.87 per 100 person-years. Compared with the TCMR group, the fully adjusted hazard ratios (HR) with 95% confidence intervals (CI) for death-censored graft failure were 1.28 (0.74-2.23) for the DSA-positive ABMR group and 1.67 (0.89-3.11) for the DSA-negative ABMR group. Furthermore, for death-uncensored graft failure, the DSA-negative group had a significantly higher risk compared with the TCMR group (HR, 1.88; 95% CI, 1.06-3.32), whereas the risk did not differ between the DSA-negative and DSA-positive group. Conclusion: DSA-negative ABMR showed a significantly higher risk for death-uncensored graft failure compared with TCMR, with a similar risk as DSA-positive ABMR. Validation study using a Korean nationwide kidney transplant cohort is ongoing together with exploration of specific causes of DSA-negative ABMR.