Microvascular Inflammation in Kidney Transplantation

Background: Microvascular inflammation (sum of glomerulitis (g) and peritubular capillaritis (ptc) scores ≥2) frequently occurs without donor-specific anti-HLA antibodies (DSA), often alongside T-cell–mediated rejection (TCMR), yet its independent prognostic significance remains uncertain. Methods: 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. Results: 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 (HR 4.33, 95%CI 2.5-7.5), TCMR (HR 4.07, 95%CI 2.3-7.1), and dnDSA (HR 4.26, 95%CI 2.2-8.3) events were each associated with death-censored allograft loss. However, in a combined time-dependent model, first TCMR (HR 2.74, 95%CI 1.4-5.4) and dnDSA (HR 2.32, 95%CI 1.1-5.1) remained independently associated with death-censored allograft loss, whereas g+ptc≥2 did not (HR 1.77, 95%CI 0.84-3.73). Conclusions: 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.