*Purpose: The factors responsible for chronic renal allograft dysfunction and premature graft loss are incompletely understood and likely multifactorial. Immunologic injury partially attributable to the formation of donor specific antibodies (DSAs) is one accepted mechanism contributing to late allograft loss. Selective co-stimulatory blockade with belatacept has demonstrated long-term improvement in glomerular filtration rate and decreased risk of death and graft loss when compared to calcineurin inhibitor (CNI) based regimens. Experimental data and post-hoc analyses of clinical trial cohorts have demonstrated a decreased rate of DSA formation with co-stimulation blockade, suggesting a possible mechanism for the benefits derived from belatacept. To date, in depth evaluation of DSA formation in belatacept-treated patients has been limited to post-hoc analyses of clinical trial cohorts. The purpose of this study is to evaluate the rate of DSA formation in a large, real-world cohort of patients treated with belatacept-based immunosuppression vs. those treated with CNI-based regimens alone.

*Methods: Retrospective review of our institutional database for all patients undergoing renal transplant at our institution between June 1, 2011 and December 31, 2018 was performed. Patient characteristics, immunosuppression protocol, and history of rejection and DSA formation were extracted from our clinical database and patient medical records. Pediatric and multi-visceral recipients were excluded.

*Results: A total of 1547 individual renal transplants met inclusion criteria and occurred during the time period specified. Of these, 1018 transplants were treated with a belatacept-based regimen, while 529 were treated with a CNI-based regimen only. A history of acute cellular rejection (ACR; Grade 1A-3) was similar between the belatacept and CNI-treated patients (32% vs 27%; P = 0.14). Belatacept-treated recipients with a history of ACR, however, were significantly more likely to have experienced multiple episodes of ACR as compared to their CNI-treated counterparts (82% vs. 41%; P <0.001). Despite this, DSA formation remained significantly lower in the belatacept group as compared to the CNI group, both in the presence of ACR (21% vs. 32%; P<0.01) and in its absence (4% vs. 12%; P<0.001).

*Conclusions: In renal transplant recipients with ACR, belatacept-treated patients experience a lower rate of DSA formation as compared to their CNI-treated counterparts, even in the setting of multiple rejection episodes. The preferential inhibition of DSA formation by belatacept may partially underlie the long-term benefits of belatacept observed in clinical trials.

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