Oxalate crystals in primary hyperoxaluria type 1 activate the NLRP3 inflammasome

Extract

Primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase, resulting in excess oxalate production and subsequent deposition of calcium oxalate crystals in the urinary tract and the renal parenchyma ultimately result in end-stage renal disease with reduced urinary oxalate excretion. This leads to systemic oxalosis with potential calcium oxalate depositions in other tissues, including the heart, blood vessels, joints, bone, retina and skin. In addition, patients often suffer from recurrent urinary tract infections and fever, although little is known about the cause of this inflammatory response. Recently, monosodium urate and calcium pyrophosphate dehydrate crystals have been reported to induce inflammation through activation of NLRP3 inflammasomes. We have studied whether calcium-oxalate is also capable of activating the NLRP3 inflammasome. …