Tocilizumab-Based Treatment of Microvascular Inflammation in Kidney Transplant Recipients: A Retrospective Study

Area of Science:

• Nephrology
• Transplantation Immunology
• Pharmacology

Background:

• Chronic-active antibody-mediated rejection (caAMR) is a primary cause of long-term kidney graft failure.
• Existing data on Tocilizumab (TCZ), an anti-IL-6 receptor antibody, for caAMR treatment are conflicting.
• Microvascular inflammation (MVI) without Donor-Specific Antibodies (DSA) and C4d deposition (MVI + DSA-C4d-) represents another challenging scenario.

Purpose of the Study:

• To evaluate the efficacy of Tocilizumab (TCZ) as a first-line therapy for kidney transplant recipients with caAMR or MVI + DSA-C4d-.
• To assess the impact of TCZ on estimated glomerular filtration rate (eGFR) trajectories and Donor-Specific Antibodies (DSA) levels.

Main Methods:

• Retrospective study of 64 adult kidney transplant recipients treated with TCZ between July 2018 and September 2023.
• Patients had caAMR or MVI + DSA-C4d- and received TCZ as first-line therapy.
• eGFR and DSA were monitored one year before and after TCZ initiation; histological data were analyzed.

Main Results:

• TCZ treatment stabilized eGFR trajectories (0.03 ± 0.2 mL/min/1.73 m²/month post-TCZ vs. -1.2 ± 0.2 mL/min/1.73 m²/month pre-TCZ; p = 0.001).
• The percentage of patients with DSA decreased significantly (63.9% to 38.9%; p < 0.001), as did mean MFI (9,537 to 7,250; p = 0.001).
• Younger age, MVI + DSA-C4d- phenotype, and lower chronic glomerulopathy scores predicted TCZ response.

Conclusions:

• First-line TCZ therapy for caAMR or MVI + DSA-C4d- kidney transplant recipients is associated with improved eGFR trajectories.
• TCZ treatment led to a reduction in DSA and MFI, alongside improvements in histological inflammation.
• These findings suggest a potential therapeutic benefit of TCZ in managing these specific kidney transplant rejection scenarios.