Antibody-Mediated Rejection in Pediatric Kidney Transplantation: Pathophysiology, Diagnosis, and Management

Abstract

Kidney transplant is the preferred treatment of pediatric end-stage renal disease. One of the most challenging aspects of pediatric kidney transplant is the prevention and treatment of antibody-mediated rejection (ABMR), which is one of the main causes of graft dysfunction and early graft loss. Most challenges are similar to those faced in adult kidney transplants; however, factors unique to the pediatric realm include naivety of the immune system and the small number of studies and randomized controlled trials available when considering pharmacological treatment options. Here, we present a case of ABMR in a pediatric patient and a review of the pathophysiology, diagnosis, and management of ABMR. ABMR in pediatric kidney transplant continues to be a frustrating condition to treat because (1) there still remain many unidentified potential antigens leading to ABMR, (2) children and adults are at different stages of their immune system development, and, thus, (3) the full pathophysiology of alloimmunity is still not completely understood, and (4) the efficacy and safety of treatment in adults may not be directly translated to children. As we continue to gain a better understanding towards the precise alloimmune mechanism that drives a particular ABMR, we can also improve pharmacotherapeutic choices. With continued research, they will become more precise in treating a particular mechanism versus using a broad scope of immunosuppression such as steroids. However, there is much more to be uncovered, such as identifying more non-human leukocyte antigens and their role in alloimmunity, determining the exact mechanism of adults achieving complete operational tolerance, and understanding the difference between pediatric and adult transplant recipients. Making strides towards a better understanding of these mechanisms will lead to continued efficacy and safety in treatment of pediatric ABMR.

Intensive Care of the Child After Kidney Transplantation

“…Acute antibody-mediated rejection (ABMR), also called humoral rejection, is one of the main causes of graft dysfunction and early graft loss (Ng et al 2015). ABMR occurs when there is deterioration in graft function associated with the development of alloreactive antibodies or donorspecific antibodies (DSAs) and characteristic histological changes on biopsy.…”

“…ABMR occurs when there is deterioration in graft function associated with the development of alloreactive antibodies or donorspecific antibodies (DSAs) and characteristic histological changes on biopsy. Diagnosis of acute ABMR involves the presence of acute graft dysfunction, as represented by elevated creatinine and decreased GFR, and should prompt a diagnostic biopsy of the allograft and serological testing for DSAs (Ng et al 2015). The Banff 2013 criteria classify ABMR based on serology and histopathologic findings of tissue and vascular endothelial injury (Haas 2014).…”

“…The Banff 2013 criteria classify ABMR based on serology and histopathologic findings of tissue and vascular endothelial injury (Haas 2014). In the immediate postoperative period, hyperacute (seconds to days) and early acute (days) ABMR may be seen (Ng et al 2015). Treatments for ABMR target the elimination of circulating allograft antibodies, immunomodulation, and/or the deactivation or inhibition of complement.…”

Unraveling the Role of Allo-Antibodies and Transplant Injury

“…Improvements in desensitization therapy have enabled management of high risk recipients, such as those with cross match-positive phenotypes and high organ transplantation sensitivity; as a result, the prevalence of severe hyper acute rejection by preformed DSAs has decreased significantly ( 7 ). Accordingly, Ng et al summarized desensitization protocols and complications using rituximab, bortezomib, eculizumab, and alemtuzumab, and reported promising graft survival in patients across various institutes ( 78 ). However, complications included anemia and thrombocytopenia, likely reflecting myelosuppression by these agents.…”

Impact of complement component 3/4/5 single nucleotide polymorphisms on renal transplant recipients with antibody-mediated rejection

“…Efficient measures, such as timely monitoring of alloreative antibodies, maintaining of adequate immunosuppressive agents, have been already taken. However, even with strict adherence, the development of ABMR still persists due to the lack of knowledge in its detailed mechanisms and the sufficiently noninvasive monitoring system for renal transplant recipients [ 7 , 8 ].…”