Purpose: We hypothesize that de novo donor specific antibody (DSA) in kidney transplant patients cause endothelial cell injury that is dependent on complement and treatment of these patients with prolonged complement inhibition will reduce endothelial cell associated transcripts (ENDATs) and mitigate antibody-mediated allograft injury. Methods: 16 subjects (5 control:11 treatment) had DSA and deteriorating renal function 12 months prior to enrollment. Treatment group received 6 months of eculizumab therapy followed by 6 months of observation, while controls were only observed. Renal biopsy samples were taken in both groups (baseline, 3m , 6m, 12m) and analyzed for ENDATs that have been associated with acute antibody-mediated injury. A priori statistical assumptions used a two-sided 0.1 significance level in this pilot study. Results: Primary endpoint was change in eGFR trajectory over time, which was assessed by linear mixed effects assuming random subject variation in baseline and eGFR slopes. Treatment group did not have greater occurrence of infections or adverse events. Treatment group had improved eGFR trajectory versus control over six months based on our predetermined 0.1 significance level, but did not reach established statistical significance(p=0.09). Within-subject analysis of treatment group patients comparing the eGFR slopes between 6 month intervals did not show a significant change(P=0.60). Modeling with baseline C1q status showed a linear relationship between C1q positivity and eGFR slope reduction(p=0.03). Renal biopsies showed an elevation of ENDATs in all subjects; however, these markers were not reduced with complement inhibition. Conclusion: We were able to show that eculizumab treatment may stabilize kidney function in patients with chronic-persistent DSA based on our lower significance threshold of 0.1. However, endothelial cell markers of antibody-mediated injury are not reduced with complement inhibition in this setting. Further studies will be necessary to identify which subsets of patients with DSA may benefit from eculizumab therapy.

CITATION INFORMATION: Kulkarni S, Kirkiles-Smith N, Deng Y, Formica R, Gilbert M, Broeckner V, Bow L, Pober J. Eculizumab for Chronic Antibody-Mediated Injury in Kidney Transplant Recipients: A Randomized-Controlled Trial. Am J Transplant. 2016;16 (suppl 3).

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