Role of Complement Properdin in Renal Ischemia-Reperfusion Injury

Abstract

Renal Ischemia-Reperfusion Injury (IRI) is one of the main causes of Acute Kidney Injury (AKI), and may lead to chronic kidney disease. The high mortality rate of AKI has not changed in the last 5 decades due to non-recognition, nephrotoxin exposure, delayed diagnosis and lack of specific intervention. Complement activation plays important roles in IRI-induced AKI because of its association with immunity, inflammation, cell death and tissue repair. Nevertheless, the role of complement properdin, the sole positive regulator of the alternative pathway, in IRI-induced AKI has not been well defined. This review evaluates the dynamic changes and underlying mechanisms of complement activation with a focus on properdin in both in vitro and in vivo models challenged by hypoxia/ reoxygenation and renal IRI. The multiple actions of properdin associated with HMGB1 and caspase-3, apoptosis and inflammation mediators, are discussed in the context of immunity, injury and repair at both the early and later stages of AKI. The complement activation-independent role of properdin and the effect of modulating properdin with or without genotype alteration are also addressed. Taking together, these might provide new mechanistic insights that potentially benefit timely diagnosis and specific intervention of IRI-induced AKI.

Keywords: Acute kidney injury.; Complement activation; Ischemia-reperfusion injury; Kidney; Properdin; Tissue repair.