The complement system is involved in several renal diseases and in renal transplantation (RTx). The authors review the complement cascade and its involvement in innate and adaptive immunity in the field of RTx. The complement cascade is involved in several steps of RTx: ischaemia—reperfusion injury (IRI), T cell-mediated acute rejection (TMR), antibody-mediated rejection (ABMR), and progressive kidney injury and fibrosis. The high frequency of complement involvement in RTx is the subject of several studies because complement could be a relevant target in treating the aforementioned conditions. There is an increasing number of ongoing clinical trials aimed at verifying the efficacy and safety of many drug candidates. The anti-C5 monoclonal antibody is already approved to prevent and treat ABMR and is the subject of trials investigating the treatment of other conditions such as IRI, TMR, and progressive fibrosis. Other molecular targets, such as C1, C3, C5a, and C5a receptor, are the subject of international trials and could prove to be effective in the near future.
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