Renal involvement in autoinflammatory diseases and inflammasome-mediated chronic kidney damage

Unprovoked activation of innate immune pathways and increased secretion of interleukin (IL)-1β and IL-18 are responsible for the protean clinical manifestations and the marked inflammatory response that characterise most hereditary autoinflammatory disorders. The kidney is a major target organ of this inflammatory process. The deposition of the acute-phase reactant serum amyloid A (SAA) as amyloid causes progressive glomerular and vascular damage and leads to organ failure. In this review we focus on the potential impact of hereditary autoinflammatory diseases on renal function, provide red flags that may guide the clinical suspicion of amyloid kidney damage and discuss the relevance of close renal monitoring for early diagnosis and prompt treatment. Moreover, NLRP3 inflammasome activation is increasingly recognised to play a key causative role in the pathogenesis of several chronic kidney diseases in which activation of caspase-1 and the proteolytic cleavage of IL-1β and IL-18 into their biologically active forms mediate glomerular and tubulointerstitial damage. Although much of the knowledge about the role of the inflammasome in kidney injury has been mostly gathered in experimental models, inhibition of IL-1 is also becoming an attractive potential therapeutic target in a variety of chronic renal disorders with a substantial inflammatory component.