Microvascular Inflammation in Kidney Transplantation

De novo donor-specific anti-HLA antibody, microvascular inflammation, and T-cell-mediated rejection events frequently occurred concomitantly or serially, and their interconnectedness and complexity are underappreciated. Microvascular inflammation without donor-specific anti-HLA antibody did not independently worsen prognosis after adjustment for serial or concomitant T-cell-mediated rejection and de novo donor-specific anti-HLA antibody events in time-dependent models. HLA-DR/DQ alloimmune risk categories were multivariable correlates of microvascular inflammation-free survival, suggesting an association with HLA mismatch.

Microvascular inflammation (sum of glomerulitis [g] and peritubular capillaritis [ptc] scores ≥2) frequently occurs without donor-specific anti-HLA antibodies (DSAs), often alongside T-cell-mediated rejection (TCMR), yet its independent prognostic significance remains uncertain.

In a consecutive single-center cohort of 689 kidney transplant recipients (2004-2021), we examined the impact of first g+ptc≥2, TCMR, and de novo DSA (dnDSA) events on death-censored allograft loss using Cox models with time-dependent covariates to account for event timing and overlap.

A first g+ptc≥2 occurred in 106/689 (15%) recipients, and 88% had concomitant or sequential TCMR and/or dnDSA. Most g+ptc≥2 biopsies were associated with TCMR (76%), including those with g=0. When assessed individually, the first g+ptc≥2 (hazard ratio [HR], 4.33; 95% confidence interval [CI], 2.5 to 7.5), TCMR (HR, 4.07; 95% CI, 2.3 to 7.1), and dnDSA (HR, 4.26; 95% CI, 2.2 to 8.3) events were each associated with death-censored allograft loss. However, in a combined time-dependent model, first TCMR (HR, 2.74; 95% CI, 1.4 to 5.4) and dnDSA (HR, 2.32; 95% CI, 1.1 to 5.1) remained independently associated with death-censored allograft loss, whereas g+ptc≥2 did not (HR, 1.77; 95% CI, 0.84 to 3.73).

In a modern tacrolimus-based cohort, g+ptc≥2 without DSA was not associated with worse outcomes after adjustment for serial or concomitant TCMR and dnDSA events.