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

Abstract

Chronic-active antibody mediated rejection (caAMR) is the leading causes of long-term kidney graft failure. Tocilizumab (TCZ), an anti-IL-6 receptor antibody, has been suggested as a treatment, but data are conflicting. We retrospectively studied consecutive adult kidney transplant recipients with caAMR or microvascular inflammation (MVI) without Donor-Specific Antibodies (DSA) and without C4d deposition (MVI + DSA-C4d-), who received TCZ as first-line therapy in two European centers. Estimated glomerular filtration rate (eGFR) and DSA were assessed one-year before and after TCZ initiation. The study included 64 patients who received TCZ between July 2018 and September 2023. The eGFR trajectory significantly decreased after TCZ treatment (-1.2 ± 0.2 vs. 0.03 ± 0.2 mL/min/1.73 m²/month pre- vs. post-TCZ, respectively; p = 0.001). The percentage of patients with DSA decreased from 63.9% to 38.9% (p < 0.001), and the average MFI decreased from 9,537 to 7,250 (p = 0.001). In multivariate analysis, younger age (OR = 0.95, p = 0.02), MVI + DSA-C4d- phenotype (OR = 5.2, p = 0.01), and lower chronic glomerulopathy score (OR = 4.5, p = 0.02) were associated with TCZ response (trajectory ≥0 after TCZ). Patient survival was 98.4%, and graft survival was 93.7% at one-year. First-line TCZ therapy for caAMR or MVI + DSA-C4d- is associated with an improvement of eGFR trajectories, reduced DSA numbers and MFI and histological inflammation in glomeruli. These data suggest a potential benefit of TCZ in these settings.

Keywords: chronic-active antibody-mediated rejection; donor-specific antibody; kidney transplantation; microvascular inflammation; tocilizumab.

Graphical abstract

FIGURE 1

Estimated glomerular filtration rate trajectories before versus after Tocilizumab treatment. Panel (A) shows the mixed linear regression between – 12 months and +12 months post-tocilizumab. Panel (B) shows the mixed linear regression between – 12 months and +24 months post-tocilizumab. Grey curves represent patient’s eGFR evolution during each period of follow-up. Time “0” corresponds to the introduction of Tocilizumab to treat antibody-mediated rejection. The p-value for the comparison of the two models, indicating the statistical significance of the difference between the two periods: pre and post tocilizumab.

FIGURE 2

Evolution of Donor-specific antibodies (DSA) and albuminuria post tocilizumab (TCZ). Panel (A) shows boxplots of urinary albuminuria over creatininuria (mg/g) at baseline and at 1-year post TCZ. Panel (B) shows the MFI of the immunodominant DSA (iDSA) at the time of diagnosis (baseline) and after 1-year post TCZ (median and SD). Panel (C) chows Pie chart of the presence of at least one DSA at the time of diagnosis (baseline) and after 1-year post TCZ treatment.

FIGURE 3

Plot of percentage of Banff Scores in biopsies before Tocilizumab (pre-TCZ) and 1-year after TCZ treatment (post-TCZ). Banff scores are g: glomerulitis, Ptc: Peritubular capilaritis, g + ptc: addition of g and ptc scores, c4d: complement deposition, cg: chronic glomerulopathy. *p-value = 0.014.