Switch from calcineurin inhibitors to belatacept in kidney transplant patients with chronic-active antibody mediated rejection results in lower decline in kidney function at three years

Abstract

Abbreviations AMBR Antibody Mediated Rejection ca-ABMR chronic-active Antibody Mediated Rejection CNI Calcineurin Inhibitors D0 Day 0 DSA Donor Specific eGFR estimated Glomerular Filtration HR Hazard Ratio KT Kidney Transplantation MFI Mean Fluorescence Intensity Donor Specific Antibodies (DSA) bind to the donor endothelial cells, ultimately resulting into allograft vasculopathy, the canonical lesion of chronic-active ABMR (ca-ABMR). Another source of chronic endothelial damages in the scope of kidney transplantation (KT) is the use of Calcineurin Inhibitors (CNI). In this setting, Belatacept, a co-stimulation blockade molecule, has emerged as an interesting alternative, improving eGFR in situations of impaired graft endothelium, such as Extended–Criteria Donors and chronic vascular changes [1]. Moreover, recent studies broaden indications of Belatacept to patients with a high immunological risk with benefits in reducing DSA titer [2]. Therefore, we conducted a retrospective multicentric study to assess the beneficial effect on KT function and survival of a switch from CNI to Belatacept in case of ca-ABMR. Based on pathology databases from four KT centers, all KT biopsies performed between 2007 and 2020 were screened and selected when they met all ca-ABMR diagnosis criteria according to Banff 2019 classification. All patients with a diagnosis of ca-ABMR and switched to Belatacept were included. The control group consisted of all patients from Rouen pathological database with a histological diagnosis of ca-ABMR who remained on CNI. Day 0 (D0) was the day of the biopsy. Detailed method is available in supplementary data 1. Nineteen patients were switched to Belatacept at the time of ca-ABMR diagnosis and compared to 58 control patients. Baseline characteristics are detailed in supplementary table S1. There was one death in the control-group at month-16, with functioning KT. After the diagnosis of ca-ABMR, there was no acute rejection in any group. At one, two and three years, death-censored KT survival in the Belatacept-treated * Tristan de Nattes [email protected]