Discussion
microangiopathy
GRAFT LOSS, ANTIBODY-MEDIATED REJECTION, VASCULAR INFLAMMATION, MICROANGIOPATHY
In this open-label randomized controlled trial, we found that preemptive treatment in patients with dnDSA was associated with a reduction in dnDSA MFI. However, compared with the use of rituximab alone, combination of IVIG to rituximab did not provide additional benefit for dnDSA reduction. dnDSA-induced vascular inflammation and microangiopathy play a major role in antibody-mediated rejection, leading to kidney allograft lossMost previous studies examined the reduction of DSA titer in pre-transplant desensitization of highly sensitized recipientsNo randomized controlled study has investigated the effectiveness of pre-emptive treatment in kidney transplant patients with dnDSA. Therefore, it is not established whether preemptive treatment for dnDSA could be useful or which treatment is better in kidney transplant patients. This randomized clinical trial showed that rituximab alone or combination therapy of rituximab and high-dose IVIG treatment reduced dnDSA MFI. However, our study did not demonstrate clear additional benefits of IVIG combination compared to rituximab alone. As clinical antibody-mediated rejection was not observed in either treatment group during the study period, we could not assess impact of each treatment on the occurrence of antibody-mediated rejection.Among class II dnDSA, anti-DQ dnDSA showed poorer response to treatment than anti-DR dnDSA. In the previous study, most of the immune-dominant DSAs detected in patients with late rejection were anti-DQ DSA and their titer did not respond well to the rejection treatmentConsidering the poor prognosis of dnDSA and the accompanying antibody-mediated rejection, early detection, and preemptive treatment of dnDSA with or without subclinical rejection could be important. Furthermore, preventive strategies are of course more important. Since class II eplet mismatch is an important immunologic risk factor for dnDSA, good eplet matching can be an important method to reduce the development of DSAThis study has several limitations. First, this study enrolled a relatively small number of patients and most of the patients had living-related kidney transplant. Therefore, the potential selection bias could not be ruled out. In addition, the short follow-up duration made it impossible to investigate preemptive treatment's effect on antibody-mediated rejection, kidney function, and graft loss. To overcome this limitation, MFI change was defined as primary endpoint in this study. Based on this study, further large-scale studies with long-term follow-up are needed to assess the long-term benefits of preemptive treatment for dnDSA. Secondly, the lack of allograft biopsy findings at the time of dnDSA detection in this study could not determine the presence of subclinical antibody-mediated rejection. However, the necessity for allograft biopsy in patients with subclinical dnDSAs has not been established in large clinical trialsNevertheless, this study is the first, randomized, controlled study to assess effectiveness of preemptive therapy for subclinical dnDSA and determine a better treatment regimen for subclinical dnDSA in kidney transplant patients. This study could contribute to the field by providing baseline data for establishing effective preemptive treatment of subclinical dnDSA.In conclusion, the preemptive administration of high-dose IVIG combined with rituximab did not show an additional benefit in reducing dnDSA compared to the administration of rituximab alone, although both treatments reduced dnDSA.