Complement in Kidney Transplantation

Abstract

The complement system is considered to be an important part of innate immune system with a significant role in inflammation processes. The activation can occur through classical, alternative, or lectin pathway, resulting in the creation of anaphylatoxins C3a and C5a, possessing a vast spectrum of immune functions, and the assembly of terminal complement cascade, capable of direct cell lysis. The activation processes are tightly regulated; inappropriate activation of the complement cascade plays a significant role in many renal diseases including organ transplantation. Moreover, complement cascade is activated during ischemia/reperfusion injury processes and influences delayed graft function of kidney allografts. Interestingly, complement system has been found to play a role in both acute cellular and antibody-mediated rejections and thrombotic microangiopathy. Therefore, complement system may represent an interesting therapeutical target in kidney transplant pathologies.

Is Early Complement Activation in Renal Transplantation Associated with Later Graft Outcome?

“…In addition, both factors are included in calculation of risk quantification for selection of deceased kidney donors [33]. Here, we suggest that these negative effects are possibly mediated by complement activation since there is a large body of evidence indicating that renal injury in transplantation is mediated by complement [1]. …”

The complex functioning of the complement system in xenotransplantation

“…There is considerable overlap between its roles in allo‐ and xenotransplantation. For example, the complement system is activated during ischemia‐reperfusion injury and is involved in antibody‐ and cell‐mediated rejection and the development of thrombotic microangiopathy and transplant vasculopathy …”

“…For example, the complement system is activated during ischemia-reperfusion injury and is involved in antibody-and cell-mediated rejection and the development of thrombotic microangiopathy and transplant vasculopathy. 87 After ischemia, tissue damage is caused when, during reperfusion, there is reduced aerobic metabolism. Oxygen radicals are generated, accompanied by inflammation, resulting in IRI (ischemia-reperfusion injury).…”

Safety and efficacy of eculizumab for the prevention of antibody-mediated rejection after deceased-donor kidney transplantation in patients with preformed donor-specific antibodies

“…[18][19][20] These patients face prolonged wait times for transplant and are disproportionately represented on transplant waitlists. 21 Eculizumab is a humanized monoclonal anti-C5 antibody that blocks the cleavage of complement component C5 and thereby inhibits the formation of terminal complement products. 1,2,4,20 Activation of the terminal complement system through the classic pathway is thought to be responsible for many of the manifestations of acute AMR.…”

“…20 As described by Jordan et al, the financial and emotional costs of maintaining highly sensitized transplant candidates on dialysis for years are extremely high, and these patients experience low quality of life and high mortality while waiting for transplant. In a rat 21 Independent Consultant, Bellevue, Washington Correspondence Denis Glotz Email: denis.glotz@aphp.fr Terminal complement products damage the capillary vascular endothelium directly through the C5b9 membrane attack complex and indirectly initiate intense, local, acute inflammatory responses through the actions of C5a, the most potent anaphylatoxin in the body.…”