Role of intrarenal complement production in kidney transplantation

Systemic complement is a major contributor to the onset and progression of kidney graft injury. However, the kidney itself is an important site of complement production. Renal-derived complement plays a key role in graft dysfunction, unlike in some other solid organ transplants. Complement factors are generated by multiple renal cell types under both physiological and pathological conditions. Renal complement production mediates ischemia/reperfusion injury and acute cellular and humoral rejection but protective effects of the complement cascade have been reported as well. More recently, intracellular complement production and activation (complosome) has also been shown to be an important regulator of key metabolic and cellular functions in renal cells and in immune kidney infiltrates, adding complexity to the field. Herein, we review current knowledge on the role of renal-derived complement in the pathophysiology of kidney graft damage and the current landscape of complement targeted therapeutics in kidney transplantation.