The signaling mechanisms that promote M2-like macrophage polarization toward CaOx nephrocalcinosis, include the ﻿NLRP3, PPARγ-miR-23-Irf1/Pknox1, miR-93-TLR4/IRF1, and miR-185-5p/CSF1 pathways.Proteomic findings have indicated that patients who form kidney stones mainly express M1-like macrophage-related proteins, which might be due to CaOx stimulation of the macrophage exosomal pathway.<h4>Conclusions</h4>This systematic review provides an update regarding the current status of macrophage involvement in CaOx nephrolithiasis. This evidence concerns the gene PKNOX1 and nephrolithiasis.