Chronic kidney disease and NLRP3 inflammasome: Pathogenesis, development and targeted therapeutic strategies

Abstract

Chronic kidney disease (CKD) is a global health concern and public health priority. The condition often involves inflammation due to the accumulation of toxins and the reduced clearance of inflammatory cytokines, leading to gradual loss of kidney function. Because of the tremendous burden of CKD, finding effective treatment strategies against inflammation is crucial. Substantial evidence suggests an association between kidney disease and the inflammasome. As a well-known multiprotein signaling complex, the NLR family pyrin domain containing 3 (NLRP3) inflammasome plays an important role in inducing renal inflammation and fibrosis. Small molecule inhibitors targeting the NLRP3 inflammasome are potential agents for the treatment of CKD.The NLRP3 inflammasome activation amplifies the inflammation response, promoting pyroptotic cell death. Thus, it may contribute to the onset and progression of CKD, but the mechanism behind inflammasome activation in CKD remains obscure.In this review, we summarized recent findings on the role of the NLRP3 inflammasome in CKD and new strategies targeting the NLRP3 inflammasome.

Keywords: ,IL-18, Interleukin-18; ASC, apoptosis-associated speck-like protein; Ang II, Angiotensin II; CKD, Chronic kidney disease; Chronic kidney disease; DAMPs, damage-associated molecular patterns; ESRD, End-stage renal disease; GFR, glomerular filtration rate; HK-2, renal tubular epithelial cells; IL-1β, Interleukin-1β; Inflammasome; Kidney function; LRR, leucine-rich repeat; NEK7, NIMA-related kinase 7; NF-kB, nuclear factor kappa-B; NLRP3, NLR family pyrin domain containing 3; NOD-like receptor; PAMPs, Pathogen-associated molecular patterns; ROS, reactive oxygen species; TXNIP, thioredoxin-interacting protein.