Novel aspects of complement in kidney injury

Abstract

Complement activation is integral to the development and progression of multiple forms of kidney disease. The liver is the principal source of serum complement, but various kidney cell types and bone marrow-derived immune cells can produce a full array of complement proteins. Locally produced and activated complement yields cleavage products that function as vital intermediaries, amplifying inflammation in ischemia-reperfusion injury and transplant rejection, among other pathological states. Additional new studies indicate that during cognate T-cell-antigen presenting cell interactions, both cell types produce alternative pathway complement components. The resultant activation products have an essential role in T-cell activation, expansion, and differentiation, which in turn has a profound impact on the development of immune-mediated kidney disease. The recognition of an expanded role for kidney cell-derived and immune cell-produced complement as pathogenic to the kidney supports the need for future studies to test the efficacy of complement inhibitors in the prevention and/or treatment of selected kidney diseases.

Markers of childhood lupus nephritis indicating disease activity

“…There is increasing evidence from animal models that the alternative pathway is importantly involved in LN [47,48]. Here, we show that in children with LN, the alternative complement pathway is indeed activated during renal flares, indicating its pathogenic significance and diagnostic value.…”

Polymorphisms in the lectin pathway of complement activation influence the incidence of acute rejection and graft outcome after kidney transplantation

“…[16][17][18][19] Moreover, complement deficiency or blockade was shown to limit postischemic reperfusion injury in various organs, and protect against acute renal transplant rejection. [20][21][22][23][24] Conflicting data exist on the deleterious versus protective role of the lectin pathway of complement activation in graft rejection, as well as in patient and graft outcomes after SOT. [25][26][27][28] Many of the available studies in kidney transplantation are either retrospective, involve small numbers of patients, or have analyzed outcomes under previous eras of immunosuppression and anti-infectious therapies.…”

Factor H and Properdin Recognize Different Epitopes on Renal Tubular Epithelial Heparan Sulfate

“…Novel aspects are the local production of complement that function as danger signals to initiate and amplify inflammatory reactions and the production of complement by immune cells, having implications for transplantation and autoimmunity (1). The AP of the complement system has been shown to play an important role in various renal diseases (2). Over-or underactivation and mutations of the complement system can result in renal injury.…”

“…Activation of the complement system occurs via three major pathways: (i) the alternative pathway (AP), 2 which is spontaneously and constantly activated on biological surfaces); (ii) the classical pathway, which is triggered by immune complexes; and (iii) the lectin pathway, which is initiated by carbohydrates on microbial surfaces. Activation of each of these pathways results in assembly of the so-called C3 convertase, followed by formation of the C5 convertase, and finally the terminal C5b-9 membrane attack complex (MAC).…”