Herein we provide, for the first time, evidence that (1) blockade of necroptosis with Nec-1 or AKF-PD can attenuate renal injury, inflammatory responses, and renal fibrosis in UUO mice and (2) the underlying mechanism seems to involve inhibition of the RIPK1/RIPK3/MLKL pathway. Here, RIPK3 is linked to renal fibrosis.