DKD involves activation of chronic inflammatory pathways that contribute to disease progression141 and is associated with multiple inflammatory cell types, molecules, and pathways, including macrophages, mast cells, and NF-κB–mediated transcription of inflammatory cytokines, including IL-1, IL-6, IL-18, and TNF.141, 142, 143, 144, 145 A signature of circulating inflammatory proteins enriched in the TNF receptor superfamily members predicted the 10-year risk of ESKD in diabetes,146 suggesting drugs targeting inflammation could help arrest progression of DKD. This evidence concerns the gene IL18 and diabetic kidney disease.