Background

Antibody-mediated rejection (ABMR) can occur in patients with pre-existing anti-HLA donor-specific antibodies (DSA) or in patients who develop de novo DSA. However, how these processes compare in terms of kidney allograft outcome has not been addressed.

Methods

From a cohort of 771 kidney biopsies from two North-American and five European centers, we included all patients with a diagnosis of ABMR. We used an integrative analysis strategy comprising a systematic assessment of clinical-biological parameters, transplant characteristics, histopathology, immunohistochemistry, type of treatment and circulating anti-HLA DSA assessment at day of transplant and at the time of ABMR.

Results

Among the 205 patients with ABMR, 103 (50%) were related to pre-existing DSA while 102 (50%) were related to de novo DSA. ABMR due to de novo DSA displayed increased proteinuria and transplant glomerulopathy lesions, lower glomerulitis, but similar peritubular-capillaritis Banff scores and C4d-deposition than patients with ABMR due to pre-existing DSA. Graft survival was superior in the group of patients with pre-existing DSA ABMR compared to patients with de novo DSA ABMR (graft survival at 8 years post ABMR of 63% vs 35% respectively, p<0.001). After adjusting for clinical, histological, immunological characteristics and treatment, we identified de novo DSA ABMR (HR=1.82 compared to pre-existing DSA ABMR); low (<30mL/min/1.73m²) eGFR at diagnosis (HR=3.273; p<0.001); ≥0.30g/g proteinuria/creatinine ratio (HR=2.44; p<0.001); and presence of cg-lesions (HR=2.25; p=0.002) as the main independent determinants of allograft loss. The inferior graft survival of patients with de novo DSA ABMR compared to pre-existing remained significant irrespective of type of treatment, time of diagnosis and degree of allograft injury and atrophy scarring at the time of diagnosis.

Conclusion

This study is the first to assess combined cohorts of ABMR due to pre-existing DSA and de novo DSA. We found that these diseases have distinct prognosis with an acceptable and superior allograft survival in patients with preexisting/persisting DSA-related ABMR compared to ABMR due to de novo DSA. This supports the transplantation of highly-sensitized patients but also encourage efforts to monitor patients for de novo DSA and avoid minimization strategies.

CITATION INFORMATION: Aubert O, Lefaucheur C, Higgins S, Hidalgo L, Duong Van Huyen J, Viglietti D, Jouven X, Glotz D, Halloran P, Loupy A. Long-Term Outcome of Antibody-Mediated Rejection Due to Pre-Existing vs. De Novo DSA in Kidney Allograft Recipients. Am J Transplant. 2017;17 (suppl 3).

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