Kidney Allograft Outcomes in Borderline and T Cell-Mediated Rejection With Microvascular Inflammation

Microvascular inflammation (MVI) is a hallmark feature of antibody-mediated rejection (ABMR), but its prognostic significance when it occurs with T-cell-mediated rejection (TCMR) in the absence of other ABMR features remains unclear.

We examined the association between pure TCMR phenotypes, defined by the presence or absence of MVI, and graft survival using restricted mean survival time (RMST), and assessed interactions with rejection involving a "v" lesion.

Among 1614 recipients with first biopsy-proven pure TCMR (2010-2023), 85% had no MVI, 8% subthreshold MVI (Banff glomerulitis [g] + peritubular capillaritis [ptc] = 1), and 7% with MVI (g + ptc ≥ 2). Compared with TCMR without MVI, recipients with TCMR + MVI (hazard ratio [HR]; 95% confidence intervals [CI] 1.57 [1.06-2.34]) had a higher risk of all-cause graft loss, whereas subthreshold MVI was not associated with increased risk. The 5-year RMST was lowest in the MVI group (3.93 [3.53-4.26]), compared with the subthreshold group (4.39 [4.11- 4.60]) and the no MVI group (4.32 [4.24-4.40]). Rejection with a "v" lesion modified this association. Recipients with TCMR + MVI and positive "v" lesion had a 2.77-fold higher risk of graft loss (2.77 [1.64-4.67]), whereas no excess risk was observed in those without vascular lesions.

Pure TCMR with MVI, particularly in the setting of a "v" lesion, represents a high-risk phenotype associated with poorer graft survival, warranting mechanistic investigations and targeted therapeutic strategies.