Fig. 4

Potential therapeutic targets for macrophage polarization in CKD. Macrophages demonstrate diverse functional phenotypes with two extreme M1 (pro-inflammatory) and M2 (anti-inflammatory) polarization states in response to renal inflammation, injury, repair and fibrosis, which implies that reduction of M1 polarization and induction of M2 polarization could be a promising therapeutic avenue for treatment of CKD. To reduce M1 polarization, inhibitors of TLRs and NLRP3 inflammasomes are promising therapeutic targets in addition to inhibition of macrophage recruitment, proliferation, and transition to myofibroblasts. Some of these agents are currently in Phase II or III trials [7]. To induce M2 polarization, ex vivo IL-4/M-CSF injection, endotoxin precondition in sepsis injured mice, and induction of M1 to M2 switch have been described [8]. However, roles of M2 macrophages in renal anti- versus pro-fibrotic pathology is controversial. Bardoxolone methyl, an activator of the Nrf2 pathway and an inhibitor of the NF-κB pathway, has been evaluated in phase I to III clinical trials for a variety of human diseases including CKD (www.clinicaltrials.gov)