The mechanisms underlying beneficial influences of low-protein diets on the progressive nature of chronic kidney disease are incompletely understood. Gao et al. identify a downregulation of Kruppel-like factor-15 (KLF15) associated with increased renal fibrosis. The KLF15 downregulation and renal fibrosis are reversed with dietary protein restriction, especially when ketoacids are added. The results suggest that KLF15 may play a role in suppressing renal fibrosis and could contribute to the benefits of dietary protein restriction.