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Impact of Everolimus Plus Calcineurin Inhibitor on Formation of Non-HLA Antibodies and Graft Outcomes in Kidney Transplant Recipients: 12-month Results from the ATHENA Substudy

Abstract

Background: Non-human leukocyte antigen (non-HLA) antibodies including antibodies targeting Angiotensin II type 1 (AT1R) and Endothelin-1 type A (ETAR) receptors represent a topic of interest in kidney transplantation (KTx). This exploratory substudy evaluated the impact of everolimus (EVR) or mycophenolic acid (MPA) in combination with tacrolimus (TAC) or cyclosporine A (CsA) in patients with preformed non-HLA antibodies, potentially associated rejections and/or their impact on renal function over 1 year.

Methods: All eligible patients were randomized (1:1:1) before transplantation to receive either EVR/TAC, EVR/CsA, or MPA/TAC regimen. The effect of these regimens on the formation of non-HLA antibodies within one year post KTx and the association with clinical events was evaluated descriptively in randomized ( = 268) population.

Results: At Month 12, in EVR/TAC group, higher incidence of patients negative for AT1R- and ETAR-antibodies (82.2% and 76.7%, respectively) was noted, whereas the incidence of AT1R- and ETAR-antibodies positivity (28.1% and 34.7%, respectively) was higher in the MPA/TAC group. Non-HLA antibodies had no influence on clinical outcomes in any treatment group and no graft loss or death was reported.

Conclusions: The studied combinations of immunosuppressants were safe with no influence on clinical outcomes and suggested minimal exposure of calcineurin inhibitors for better patient management.

Clinical Trial Registration: https://clinicaltrials.gov/ (NCT01843348; EudraCT number: 2011-005238-21).

Citing Articles

The Influence of Anti-ETAR and Anti-CXCR3 Antibody Levels on the Course of Specific Glomerulonephritis Types.

Szymczak M, Heidecke H, Zabinska M, Janek L, Wronowicz J, Kujawa K J Clin Med. 2025; 13(24.

PMID: 39768675 PMC: 11679591. DOI: 10.3390/jcm13247752.

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