Highly Sensitized Candidates Remain at Risk for Microvascular Inflammation Even When Donor-specific Antibody Is Avoided: A Matched Cohort Study

Abstract

Background. Microvascular inflammation (MVI) is a key feature of antibody-mediated rejection (AMR) among patients with HLA donor-specific antibody (DSA), but MVI at AMR thresholds (Banff glomerulitis [g] + peritubular capillaritis [ptc] score ≥ 2) without DSA has been increasingly recognized. We aimed to determine the incidence of MVI among highly sensitized kidney transplant recipients without DSA. Methods. We performed a single-center, retrospective, matched cohort study comparing outcomes of kidney transplant recipients with cPRA ≥90% with preexisting DSA (n = 49), cPRA ≥90% without preexisting DSA (n = 47), and matched controls with cPRA = 0 without preexisting DSA (n = 49). Controls were matched by age, donor type, and transplant date. Indication and surveillance biopsies combined with annual de novo DSA screening were obtained. Results. Kidney transplant recipients with a cPRA ≥90% and no evidence of preexisting or de novo DSA had a higher incidence of MVI (glomerulitis + peritubular capillaritis ≥ 2) than patients with cPRA = 0 [35% (17/49) versus 12% (6/49), P = 0.0003] over a median (interquartile range) follow-up of 5 (4–6) y posttransplant. Among this cPRA ≥90% group without DSA, MVI persisted in 54% of cases on follow-up biopsy (7/13), and 24% (4/13) of cases developed transplant glomerulopathy (Banff cg score > 0). Conclusions. Highly sensitized transplant recipients have a high incidence of persistent and progressive MVI, even without DSA. The mechanisms underlying these histologic features needs to be elucidated, but this information is important to consider when making decisions about transplantation among highly sensitized individuals.