NLRP3 Inflammasome Activation in Renal Injury: Long-Term Effectiveness and Safety of Blocking the IL-1 System in a Kidney Transplanted Patient Affected by AA Amyloidosis Secondary to Cryopyrin-Associated Periodic Syndromes (CAPS)

Abstract

NLRP3 inflammasome activation is recognized to play a key role in the pathogenesis of several chronic diseases such as chronic tubulointerstitial diseases, glomerulonephritis and calcium oxalate crystal nephropathy. Genetic variants of NLPR3 are likely associated to pro-inflammatory/autoimmune disorders, by the altered self-regulation of inflammasome with overproduction of inflammatory cytokines. Recently experimental and human studies have focused on the interest in both acute and chronic renal diseases. Inhibition of the Interleukin-1 (IL-1) system has become an attractive potential therapeutic target in a variety of renal disorders, including IgA nephropathy, ischemic reperfusion injury, after unilateral ureteral obstruction, rhabdomyolisys-induced Acute Kidney Injury (AKI), contrast-induced AKI, crystalline nephropathy, and recently also in diabetic nephropathy.NLRP3 activation in kidney diseases magnify inflammation and subsequent fibrosis, and this effect is abrogated by genetic or pharmacologic deletion of NLRP3. Inflammasome-dependent NLRP3 mediates the progression of kidney diseases by rapidly increasing the inflammatory response in immune cells as demonstrated also in hereditary autoimmune syndromes, like CAPS. We describe the renal involvement in one patient affected by Muckle-Wells syndrome (MWS), biopsy-proven reactive AA amyloidosis and proteinuric renal failure, by focusing the interest above all on the efficacy and safety profile of therapy with anti-IL1 antibody on a clinical continuum from the reduced renal function to the kidney transplant.