Treatment of Chronic Active Antibody-mediated Rejection With Pulse Steroids, IVIG, With or Without Rituximab is Associated With Increased Risk of Pneumonia

Abstract

Background. The risk of infection associated with specific treatments of chronic active antibody-mediated rejection (cAMR) after kidney transplantation remains unknown. Methods. This was a single-center study of kidney transplant recipients treated with pulse steroids, intravenous immunoglobulin (IVIG) ± rituximab for biopsy-confirmed cAMR. The control group consisted of age- and race-matched patients who underwent donor-specific antibody-based protocol biopsies but had no rejection. We collected data on BK virus (BKV), cytomegalovirus (CMV), urinary tract infection (UTI), and pneumonia postbiopsy. Results. There were 49 patients in each group. In those with cAMR, 21 (43%) were treated with steroids, IVIG, and rituximab; the remaining received steroids and IVIG only. The risk of graft failure was greater in the cAMR group [22 (45%) vs. 3 (6%), P < 0.001]. Kaplan-Meier analyses demonstrated a significantly greater risk of pneumonia in the cAMR group (P = 0.02). This was confirmed by multivariable Cox regression analyses [Hazard ratio (HR) = 6.04, P = 0.027, 95% CI, 1.22-29.75]. None of the patients with pneumonia were affected by opportunistic pathogens. Additionally, the risk of CMV, UTI, and BKV was not increased. Rituximab was not independently associated with any of the infections studied. Conclusions. Treatment of cAMR, but not rituximab, was associated with a 6-fold increased risk of pneumonia. Additional studies are needed to determine the safety and efficacy of prolonged antimicrobial prophylaxis and monitoring strategies, including for hypogammaglobulinemia, to reduce the risk of pneumonia following the treatment of cAMR.