PURPOSE OF REVIEW: Eculizumab suppresses the effector functions of the complement system and represents a therapeutic breakthrough for patients with paroxysmal nocturnal hemoglobinuria or atypical hemolytic uremic syndrome (aHUS). Safety monitoring is ongoing; so far, most notable is the expected increase in infection risk with encapsulated organisms. Despite potential applicability in multiple complement-mediated disorders, the off-label use of eculizumab has been limited, mainly by its prohibitive cost. The purpose of this review is to summarize the current data relevant to the use of eculizumab in kidney transplantation. RECENT FINDINGS: In aHUS, prone to high rates of recurrence and allograft loss, eculizumab has made the most notable therapeutic impact. Further clarification of complement defects may help predict therapeutic responses and hopefully guide treatment duration. In C3 glomerulopathies, the clinical response to eculizumab appears more heterogeneous and less effective in processes mediated by upstream to C5 complement deregulation. A large clinical trial of eculizumab for prevention of delayed graft function is ongoing. In antibody-mediated rejection, the role of eculizumab is unclear as its use has been limited to very complex, mostly presensitized, patients in mixed combinations of therapeutic modalities. SUMMARY: Overall, eculizumab has raised awareness of complement-mediated disorders as an exciting, new therapeutic option with multiple potential applications in kidney transplantation. Further research is needed to develop a better understanding of eculizumab applicability, efficacy, and treatment monitoring and beyond, to future therapeutic tools targeting the complement.
PURPOSE OF REVIEW: Eculizumab suppresses the effector functions of the complement system and represents a therapeutic breakthrough for patients with paroxysmal nocturnal hemoglobinuria or atypical hemolytic uremic syndrome (aHUS). Safety monitoring is ongoing; so far, most notable is the expected increase in infection risk with encapsulated organisms. Despite potential applicability in multiple complement-mediated disorders, the off-label use of eculizumab has been limited, mainly by its prohibitive cost. The purpose of this review is to summarize the current data relevant to the use of eculizumab in kidney transplantation. RECENT FINDINGS: In aHUS, prone to high rates of recurrence and allograft loss, eculizumab has made the most notable therapeutic impact. Further clarification of complement defects may help predict therapeutic responses and hopefully guide treatment duration. In C3 glomerulopathies, the clinical response to eculizumab appears more heterogeneous and less effective in processes mediated by upstream to C5 complement deregulation. A large clinical trial of eculizumab for prevention of delayed graft function is ongoing. In antibody-mediated rejection, the role of eculizumab is unclear as its use has been limited to very complex, mostly presensitized, patients in mixed combinations of therapeutic modalities. SUMMARY: Overall, eculizumab has raised awareness of complement-mediated disorders as an exciting, new therapeutic option with multiple potential applications in kidney transplantation. Further research is needed to develop a better understanding of eculizumab applicability, efficacy, and treatment monitoring and beyond, to future therapeutic tools targeting the complement.
Authors: Saif A Khan; Dawood Al-Riyami; Yasser W Al-Mula Abed; Saja Mohammed; Marwa Al-Riyami; Nabil M Al-Lawati Journal: Sultan Qaboos Univ Med J Date: 2016-08-19
Authors: Anna-Luisa Volk; Francis Jingxin Hu; Magnus M Berglund; Erik Nordling; Patrik Strömberg; Mathias Uhlen; Johan Rockberg Journal: Sci Rep Date: 2016-08-11 Impact factor: 4.379
Authors: Alex Macpherson; Xiaofeng Liu; Neesha Dedi; Jeffery Kennedy; Bruce Carrington; Oliver Durrant; Sam Heywood; Jean van den Elsen; Alastair D G Lawson Journal: J Biol Chem Date: 2018-07-20 Impact factor: 5.157