Association Between Peripheral Blood CD19-Positive Rate and Antibody-Mediated Rejection Following Rituximab Administration in Kidney Transplant Recipients

Abstract

Background. Rituximab is used widely for desensitization in ABO-incompatible and donor-specific antibody-positive kidney transplantation. However, data about the effects of individual differences in rituximab-induced B-cell suppression on antibody-mediated rejection (AMR) remain unknown. We aimed to assess the association between CD19-positive rate and AMR following rituximab administration after kidney transplantation. Methods. Overall, 42 patients who underwent rituximab therapy for pretransplant desensitization in ABO-incompatible (n = 33) and donor-specific antibody-positive (n = 15) kidney transplantation were observed retrospectively. To predict AMR incidence, the peripheral blood CD19-positive rate was determined and classified into short- and long-acting groups. AMR incidence, allograft function, complications, and rituximab dose were compared. Results. Eight patients (19%) had AMR within 39.2 months after transplantation. The CD19-positive rate cutoff value to predict AMR incidence was 4.4%, 6.4%, and 7.7% at 6, 12, and 18 months after transplantation, respectively. When comparing the short- and long-acting groups stratified according to the CD19-positive rate cutoff value, AMR incidence was significantly higher in the short-acting group than in the long-acting group at 6 (71.4% vs 8.6%), 12 (70.0% vs 3.1%), and 18 (58.3% vs 3.3%) months after transplantation. The CD19-positive rate for all patients with AMR exceeded the cutoff value 6, 12, or 18 months. Conversely, serum creatinine level, tacrolimus trough-level, cytomegalovirus antigenemia-positive rate, neutropenia incidence rate, and total dose of rituximab before transplantation showed no significant differences between the 2 groups. Conclusions. The risk of AMR was higher in patients with short-term B-cell suppression following rituximab administration. Additional rituximab administration after transplantation may prevent AMR in patients with a CD19-positive rate higher than the cutoff value.

Burden of neutropenia and leukopenia among adult kidney transplant recipients: A systematic literature review of observational studies

“…Subsequently, a total of 75 papers were excluded during either full‐text screening or data extraction. Ultimately, 82 citations 2,6–86 including 65,386 participants met inclusion criteria.…”

“…A total of 27 studies reported neutropenia incidence 2 , 6,11,14,15,26,30,31,34,36,39,42,44,46–48,51,60,63,64,68,69,75,76,78,81,85 . The absolute neutrophil count (ANC) threshold to define neutropenia varied widely; the majority of the studies ( n = 12) reported neutropenia with a threshold of ANC <1000/μl 2,6,11,15,26,36,44,51,63,75,81,85 followed by a threshold of <500/μl ( n = 8 11,26,34,42,44,60,81,85 ), <1500/μl ( n = 7 26,44,46,60,68,76,81 ), and <2000/μl ( n = 3 64,78,81 ); in 7 studies 14,30,39,42,47,48,69 , a threshold definition was not reported. In 1 study, 31 neutropenia was defined using an International Classification of Diseases, Ninth Revision (ICD‐9) code.…”