title: Molecular mechanisms of crystal-related kidney inflammation and injury. Implications for cholesterol embolism, crystalline nephropathies and kidney stone disease.
abstract: Crystals are particles of endogenous inorganic or organic composition that can trigger kidney injury when deposited or formed inside the kidney. While decades of research have focused on the molecular mechanisms of solute supersaturation and crystal formation, the pathomechanisms of crystal-induced renal inflammation remain largely unknown. The recent discovery of the intracellular NLRP3 inflammasome as a pattern recognition platform that translates crystal uptake into innate immune activation via secretion of IL-1β and IL-18 revised the pathogenesis of gout, silicosis, asbestosis, atherosclerosis and other crystal-related disorders. As a proof of concept, the NLRP3 inflammasome was now shown to trigger inflammation and acute kidney injury (AKI) in oxalate nephropathy. It seems likely that this and potentially other innate immunity mechanisms drive crystalline nephropathies (CNs) that are associated with crystals of calcium phosphate, uric acid, cysteine, adenine, certain drugs or contrast media, and potentially of myoglobin during rhabdomyolysis and of light chains in myeloma. Here, we discuss the proven and potential mechanisms of renal inflammation and kidney injury in crystal-related kidney disorders. In addition, we list topics for further research in that field. This perspective may also provide novel therapeutic options that can help to avoid progressive tissue remodeling and chronic kidney disease in patients with kidney stone disease or other CNs.
authors.affiliation: Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig Maximilians Universität-Innenstadt, Munich 80336, Germany.
authors.forename: Shrikant R
authors.initials: SR
authors.lastname: Mulay
authors.forename: Andrew
authors.initials: A
authors.lastname: Evan
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Anders
mesh_terms: D000818:Animals; D017700:Embolism, Cholesterol / Q000276:immunology / Q000378:metabolism*; D006073:Gout / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000502:physiology; D007668:Kidney / Q000098:blood supply / Q000276:immunology / Q000473:pathology; D007669:Kidney Calculi / Q000276:immunology / Q000378:metabolism*; D009393:Nephritis / Q000276:immunology / Q000378:metabolism*; D014527:Uric Acid / Q000378:metabolism
chemical_list: D058847:Inflammasomes; D014527:Uric Acid
keywords: cystinosis; gout; myeloma cast nephropathy; nephrolithiasis; rhabdomyolysis