One of the major issues in the clinical management of kidney recipients with ABMR is the lack of early and reliable markers that surrogate long-term graft outcomes. We investigated the role of C1q-binding anti-HLA DSAs for decision making in kidney recipients with ABMR receiving standard of care (SOC) treatment.

Among 1196 kidney recipients (2008-2011), we prospectively enrolled all patients with biopsy-proven active ABMR according to the most recent Banff criteria, who received standardized treatment (plasma exchange, high-dose intravenous immunoglobulin, rituximab and steroids). Patients were systematically assessed at ABMR diagnosis and 3-month post-treatment initiation for clinical data, histological characteristics and DSA characteristics (specificity, MFI, C1q-binding capacity).

We included 139 kidney recipients with ABMR diagnosed at a median time of 15.5 months (IQR, 5.8-36.8) post-transplant receiving SOC treatment. At ABMR diagnosis, pts with C1q-binding DSAs (N=91, 65%) showed similar 6-year graft survival compared to pts with non-C1q-binding DSAs (N=48, 35%) (66% vs 83%, p=0.072). At the time of post-treatment evaluation, pts with C1q-binding DSAs (N=38, 27%) had decreased 6-year graft survival compared to pts with non-C1q-binding DSAs (N=101, 73%) (44% vs 83%, p<0.001). After adjusting for GFR, proteinuria, all histological Banff scores and DSA characteristics, post-treatment C1q-binding DSAs were independent predictors of graft loss (adjusted HR=2.6, p=0.007) and outperformed DSA MFI level to predict graft loss (increase in C-statistic from 0.63 to 0.68; cNRI: 0.83, P<0.001; IDI: 0.08, P=0.002). We built a conditional inference tree for evidence-based clinical decision making including the most informative variables after treatment (accuracy: 0.77): GFR, presence of cg and presence of C1q-binding DSA. The decision tree segregated 5 groups of pts with distinct outcomes; for instance, pts with GFR>33 mL/min and without C1q-binding DSA showed a 5-year graft survival of 93% vs 35% in pts with GFR≤33 mL/min, without cg and with C1q-binding DSA.

C1q-binding anti-HLA DSAs are strong and independent predictors of long-term kidney allograft loss after SOC treatment of ABMR and allowed to build a clinical decision tree showing high accuracy in risk stratifying outcomes.

CITATION INFORMATION: Lefaucheur C., Viglietti D., Bouatou Y., Aubert O., Zeevi A., Loupy A. C1q-Binding Donor-Specific Anti-HLA Antibodies for Clinical Decision Making in Kidney Recipients with Antibody-Mediated Rejection Receiving Standard of Care Treatment Am J Transplant. 2017;17 (suppl 3).

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