Targeting the Roots of Kidney Disease: Systematic Review of the Therapies Targeting the Complement System.

Background/

Objectives

The field of nephrology is increasingly embracing advanced treatments and clinical trials that focus on inhibiting specific components of the complement cascade, a key driver in complement-mediated kidney diseases. Materials and

Methods

This review aims to summarize innovative therapies targeting various pathways, including the inhibition of the terminal part of the complement pathway (mainly C5), the alternative pathway (factor B inhibitors), and the lectin pathway (MASP inhibitors. C5 inhibitors play a critical role in preventing the formation of the membrane attack complex (MAC), offering effective solutions for conditions like atypical hemolytic uremic syndrome (aHUS) and paroxysmal nocturnal hemoglobinuria (PNH). Meanwhile, avacopan, a C5a receptor antagonist, addresses ANCA-associated vasculitis (AAV) by mitigating inflammation and enabling reduced reliance on corticosteroids. Similarly, narsoplimab, which inhibits MASP-2, targets the lectin pathway implicated in conditions such as aHUS. Iptacopan, a factor B inhibitor, focuses on the alternative pathway and demonstrates efficacy in managing C3 glomerulopathy (C3G).

Results

A systematic review of complement-targeted therapies was conducted, analysing studies from 2013 to 2023 that address unmet medical needs in primary and secondary glomerular diseases.

Conclusions

Our systematic review of complement-targeted therapies shows that these tailored and innovative treatments may specifically address unmet medical needs in primary and secondary glomerular diseases.