Higher Donor Age and Severe Microvascular Inflammation Are Risk Factors for Chronic Rejection After Treatment of Active Antibody-Mediated Rejection

Abstract

Recent developments in intensive desensitization protocols have enabled kidney transplantation in human leukocyte antigen (HLA)-sensitized recipients. However, cases of active antibody-mediated rejection (AABMR), when they occur, are difficult to manage, graft failure being the worst-case scenario. We aimed to assess the impact of our desensitization and AABMR treatment regimen and identify risk factors for disease progression. Among 849 patients who underwent living-donor kidney transplantation between 2014 and 2021 at our institution, 59 were diagnosed with AABMR within 1 year after transplantation. All patients received combination therapy consisting of steroid pulse therapy, intravenous immunoglobulin, rituximab, and plasmapheresis. Multivariable analysis revealed unrelated donors and preformed donor-specific antibodies as independent risk factors for AABMR. Five-year death-censored graft survival rate was not significantly different between patients with and without AABMR although 27 of 59 patients with AABMR developed chronic AABMR (CABMR) during the study period. Multivariate Cox proportional hazard regression analysis revealed that a donor age greater than 59 years and microvascular inflammation (MVI) score (g + ptc) ≥4 at AABMR diagnosis were independent risk factors for CABMR. Our combination therapy ameliorated AABMR; however, further treatment options should be considered to prevent CABMR, especially in patients with old donors and severe MVI.

Keywords: Banff classification; antibody-mediated rejection; graft survival; kidney transplantation; treatment outcomes.

FIGURE 1

Development of active antibody-mediated rejection (AABMR) within 1 year after kidney transplantation Kaplan-Meier curves for AABMR-free survival between (A) relative and unrelated donors, (B) primary and multiple kidney transplantation (KTx), and (C) positive and negative for preformed donor-specific antibody (DSA). p-values calculated by Log-rank tests were shown.

FIGURE 2

Five-year death-censored graft survival rate between active antibody-mediated rejection (AABMR) and non-AABMR groups. The graft survival rates were compared between patients with AABMR within 1 year of kidney transplantation and those without it. The five-year death-censored graft survival rates did not differ between the groups. Kaplan-Meier curves depicting the five-year death-censored graft survival rate from kidney transplantation were presented, and the p-value was calculated using the Log-rank test.

FIGURE 3

The treatment regimen for active antibody-mediated rejection. Y-axis: number of patients. Steroid pulse therapy, methylprednisolone, 250–2,500 mg/body; intravenous immunoglobulin (IVIG) therapy, 0.5–5.2 g/kg; rituximab administration, 200–300 mg/body; plasmapheresis, 2–10 times including plasma exchange or double-filtration plasmapheresis with fresh frozen plasma or albumin replacement.

FIGURE 4

Development of chronic active antibody-mediated rejection (CABMR). Kaplan-Meier curves of the CABMR-free rate after AABMR diagnosis comparing (A) the patients with donor ages of ≥59 and <59 years (p = 0.01); and (B) the patients with MVI score ≥4 and <4 at diagnosis of AABMR (p = 0.005). p-values calculated by the Log-rank test were shown.