Successful Salvage Treatment of Resistant Acute Antibody-Mediated Kidney Transplant Rejection with Eculizumab

Abstract

Antibody-mediated rejection (ABMR) jeopardises short-and long-term transplant survival and remains a challenge in the field of organ transplantation. We report the first use of the anticomplement agent eculizumab in Oman in the treatment of a 61-year-old female patient with ABMR following a living unrelated kidney transplant. The patient was admitted to the Sultan Qaboos University Hospital in Muscat, Oman, in 2013 on the eighth day post-transplantation with serum creatinine (Cr) levels of 400 µmol/L which continued to rise, necessitating haemodialysis. A biopsy indicated ABMR with acute cellular rejection. No improvement was observed following standard ABMR treatment and she continued to require dialysis. Five doses of eculizumab were administered over six weeks with a subsequent dramatic improvement in renal function. The patient became dialysis-free with serum Cr levels of 119 µmol/L within four months. This case report indicates that eculizumab is a promising agent in the treatment of ABMR.

The role of anticomplement therapy in the management of the kidney allograft

“…The authors emphasized the need to modify the therapeutic approach since eculizumab therapy was offered when all other therapeutic alternatives had failed and considerable cortical necrosis and fibrosis had already occurred 47 . Similar conflicting results were also reported in other case series 48–57 …”

“…47 Similar conflicting results were also reported in other case series. [48][49][50][51][52][53][54][55][56][57] Another single-center retrospective study involving 102 kidney transplant recipients with biopsy-proven AMR who were treated initially with plasmapheresis or immunoadsorption, followed by a single course of IVIG, and in the case of nonresponse or recurrence, with added additional immunosuppressive medications, such as rituximab, bortezomib, thymoglobulin, or eculizumab. 58 However, only three patients received eculizumab, so, from the point of view of eculizumab, it amounted to a case series.…”

Applications of Transcriptomics in the Research of Antibody-Mediated Rejection in Kidney Transplantation: Progress and Perspectives

“…Likewise, studies evaluating the beneficial effect of eculizumab, a humanized monoclonal antibody that binds to the human C5 complement protein, have reported mixed results in treating ABMR. 29–31 Therefore, there is a constant unmet need for increasing the diagnostic precision in ABMR and in-depth knowledge of the interplay between the immune and nonimmune cells in the onset and progression of ABMR.…”

Inhibition of Complement

“…With the recent reports of complement component 5 (C5) inhibition with eculizumab providing an efficient way to combat antibody mediated rejection 8 and atypical hemolytic uremic syndrome 9 after kidney transplants, these are exciting times to be following the ongoing preclinical and clinical efforts in complement inhibition. The current knowledge of complement inhibition, particularly the clinical utility of plasma-derived C1 inhibitor are reviewed recently 10 and make for an engaging reading.…”