Despite advancements in the care of lupus nephritis, a considerable proportion 
of patients may respond poorly or flare while on conventional immunosuppressive 
agents. Studies in murine and human lupus have illustrated a pathogenic role for 
several cytokines by enhancing T- and B-cell activation, autoantibodies 
production and affecting the function of kidney resident cells, therefore 
supporting their potential therapeutic targeting. To this end, there is limited 
post-hoc randomized evidence to suggest beneficial effect of belimumab, 
administered on top of standard-of-care, during maintenance therapy in lupus 
nephritis. Type I interferon receptor blockade has yielded promising results in 
preliminary SLE trials yet data on renal activity are unavailable. Conversely, 
targeting interleukin-6 and interferon-γ both failed to demonstrate a 
significant renal effect. For several other targets, preclinical data are 
encouraging but will require confirmation. We envision that high-throughput 
technologies will enable accurate patient stratification, thus offering the 
opportunity for personalized implementation of cytokine-targeting therapies.