Abstract

Kidney transplantation is a life-saving strategy for patients with end-stage renal diseases. Despite the advances in surgical techniques and immunosuppressive agents, the long-term graft survival remains a challenge. Growing evidence has shown that the complement system, part of the innate immune response, is involved in kidney transplantation. Novel insights highlighted the role of the locally produced and intracellular complement components in the development of inflammation and the alloreactive response in the kidney allograft. In the current review, we provide the updated understanding of the complement system in kidney transplantation. We will discuss the involvement of the different complement components in kidney ischemia–reperfusion injury, delayed graft function, allograft rejection, and chronic allograft injury. We will also introduce the existing and upcoming attempts to improve allograft outcomes in animal models and in the clinical setting by targeting the complement system.

Highlights

  • Ruochen Qi and Weijun Qin*Reviewed by: Marina Noris, Mario Negri Pharmacological Research Institute (IRCCS), Italy

  • Kidney transplantation is the preferred treatment for patients with end-stage renal diseases (ESRDs), which greatly improves their quality of life

  • NCT01895127, a study that evaluated the efficacy of eculizumab treatment in kidney transplant recipients with biopsy-proven antibody-mediated rejection (AMR), failed to demonstrate the superiority of eculizumab compared with standard plasmapheresis and immunoglobin treatment

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Summary

Ruochen Qi and Weijun Qin*

Reviewed by: Marina Noris, Mario Negri Pharmacological Research Institute (IRCCS), Italy. Kidney transplantation is a life-saving strategy for patients with end-stage renal diseases. Growing evidence has shown that the complement system, part of the innate immune response, is involved in kidney transplantation. Novel insights highlighted the role of the locally produced and intracellular complement components in the development of inflammation and the alloreactive response in the kidney allograft. We provide the updated understanding of the complement system in kidney transplantation. We will discuss the involvement of the different complement components in kidney ischemia– reperfusion injury, delayed graft function, allograft rejection, and chronic allograft injury. We will introduce the existing and upcoming attempts to improve allograft outcomes in animal models and in the clinical setting by targeting the complement system

INTRODUCTION
OVERVIEW OF THE COMPLEMENT SYSTEM
Initiation Phase
Activation Phase
Complement Regulatory Factors
Complement Receptors
Complement Pathway Triggered in Kidney IRI
Involvement of Complement Regulators in Kidney IRI
Involvement of Complement Receptors in Kidney IRI
Complement Components Interact With Coagulation Factors
Consequences of Complement Activation in Kidney IRI
Complement as a Therapeutic Target of Kidney IRI in Animal Models
Complement Activation Contributes to DGF
Complement Factors as Biomarkers to Predict DGF
Ex Vivo Inhibition of Complement Activation to Prevent DGF
Regulation of Complement Components in Dendritic Cells
ROLE OF COMPLEMENT IN ANTIBODYMEDIATED REJECTION
COMPLEMENT ACTIVATION IN CHRONIC ALLOGRAFT INJURY
TARGETING COMPLEMENT ACTIVATION IN KIDNEY TRANSPLANT RECIPIENTS
Phase II
Phase II Phase III Phase III Phase II
Not yet recruiting
CONCLUSION AND FUTURE PERSPECTIVES

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