# Complement in Antibody-Mediated Rejection of the Kidney Graft: From Pathophysiology to Clinical Practice

## TL;DR

This paper explores how the complement system contributes to kidney transplant rejection and discusses new treatments targeting this system.

## Contribution

The paper highlights the role of complement activation in AMR and introduces emerging therapies like complement inhibitors.

## Key findings

- Complement activation is crucial in antibody-mediated kidney transplant rejection.
- C4d positivity is no longer mandatory for AMR diagnosis but predicts poor outcomes.
- Complement inhibitors like eculizumab and C1 inhibitors are effective in treating AMR.

## Abstract

Antibody-mediated rejection (AMR) is a leading cause of kidney graft failure. Complement activation is involved in the AMR process. Our aim is to provide the current understanding of the pathophysiology related to complement-mediated injury in AMR, to present the current evidence regarding complement blockade in AMR management, and to point out emerging therapies and future directions in this area. The complement system plays an important role in the onset and progression of AMR. There is a balance between complement-dependent and -independent mechanisms in the development of rejection lesions. Classic and leptin pathways are involved in this process. C4d positivity is no longer a mandatory feature for AMR diagnosis but remains an independent predictor of negative outcomes. The current evidence regarding AMR treatment is limited. Terminal and proximal complement blockade has gained recognition in clinical practice. Eculizumab and C1 inhibitors are effective in the treatment of AMR as adjuvant therapies to the standard of care. The availability of novel complement inhibitors will lead to more effective and tailored treatment strategies.