Crystal nephropathies: mechanisms of crystal-induced kidney injury

Key Points Crystals cause several types of kidney injury: renovascular damage (type 1), tubular damage (type 2), and urolithiasis (type 3) Renovascular damage (type 1) due to cholesterol crystals (from plaques in cholesterol embolism, for example) leads to ischaemic renal necrosis; stenotic atherosclerosis of renal arteries causes renal atrophy owing to chronic ischaemia Tubular crystallopathy type 2 involves crystals of endogenous metabolites, minerals or proteins or exogenous drugs and toxins and causes acute necroinflammation, tubule obstruction or crystal granuloma formation and chronic tissue remodelling In urolithiasis (type 3 crystallopathy), crystals form at the papilla or in the ducts of Bellini and grow to form calculi and stones, which cause colic, infections, and obstruction-related nephron loss The molecular mechanisms of crystal-induced tissue injury and remodeling have become an exciting area of basic and translational research Crystals can trigger different types of renal injury according to their speed at which they form and their localization. Here, the authors discuss shared and specific mechanisms underlying crystal formation and renal injury, such as regulated cell death and inflammasome activation. Crystals can trigger a wide range of kidney injuries that can lead to acute kidney injury, chronic kidney disease, renal colic or nephrocalcinosis, depending on the localization and dynamics of crystal deposition. Studies of the biology of crystal handling by the kidney have shown that the formation of different crystals and other microparticles and the associated mechanisms of renal damage share molecular mechanisms, such as stimulation of the NLRP3 inflammasome or direct cytotoxicity through activation of the necroptosis signalling pathway. By contrast, crystal granuloma formation is limited to chronic crystallopathies that lead to chronic kidney disease and renal fibrosis. Here, we discuss current understanding of the pathomechanisms underlying the different types of crystal-induced kidney injury and propose a classification of crystal nephropathies based on the localization of crystal deposits in the renal vasculature (type 1), the nephron (type 2), or the draining urinary tract (type 3). Further exploration of the molecular mechanisms of crystal-induced kidney injury and renal remodelling might aid the development of innovative cures for these diseases.