Abstract
Introduction: Chronic antibody-mediated rejection (cAMR) has very few effective therapeutic options. Interleukin-6 is an attractive target because it is involved in inflammation and humoral immunity. Therefore, the use of tocilizumab (anti-IL6 receptor, TCZ) is a potential valuable therapeutic option to treat cABMR in kidney-transplant (KT) recipients.Materials and Methods: This single-center retrospective study included all KT recipients that received monthly TCZ infusions in the setting of cABMR, between August 2018 and July 2021. We assessed 12-month renal function and KT histology during follow-up.Results: Forty patients were included. At 12-months, eGFR was not significantly different, 41.6 ± 17 vs. 43 ± 17 mL/min/1.73 m2 (p = 0.102) in patients with functional graft. Six patients (15%) lost their graft: their condition was clinically more severe at the time of first TCZ infusion. Histological follow-up showed no statistical difference in the scores of glomerulitis, peritubular capillaritis, and interstitial fibrosis/tubular atrophy (IFTA). Chronic glomerulopathy score however, increased significantly over time; conversely arteritis and inflammation in IFTA ares improved in follow-up biopsies.Conclusion: In our study, the addition of TCZ prevented clinical and histological worsening of cABMR in KT recipients, except for more severely ill patients. Randomized studies are needed to clarify the risk/benefit of TCZ in cABMR.
Highlights
Chronic antibody-mediated rejection has very few effective therapeutic options
The most frequent primary or secondary causes leading to graft failure were intercurrent medical events in 36.3% of graft failures followed by T cell-mediated rejection (TCMR) in 34% and ABMR in 30.7%
In the present single-center study, we report on the long-term effects on tocilizumab monthly therapy in kidney transplant recipients presenting with chronic antibody-mediated rejection (cABMR) and/or transplant glomerulopathy
Summary
Chronic antibody-mediated rejection (cAMR) has very few effective therapeutic options. Kidney transplantation remains the best therapeutic option regarding end-stage kidney disease for various reasons including improved survival and quality-of-life compared to those receiving dialysis therapy [1–4] the half-life of kidney transplants has not changed that much within the last decades at least in the United States as demonstrated by Lamb et al This was the case in low-risk populations like livingdonor-recipients where half-life was 11.4 years in 1989 and 11.9 years in 2005. In 2012 Sellarés et al have shown in a prospective cohort of 315 allograft recipients who underwent indication biopsies at 6 days to 32 years posttransplant that many actual failures after indication biopsies manifest phenotypic features of antibody-mediated (ABMR) or mixed rejection. They underscore the major role of non-adherence [6]. In 77.9%, a primary cause could be attributed to graft loss, of which ABMR was the most frequent etiology (21.5%)
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