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Nanoscale Analysis of Randall's Plaques by Electron Energy Loss Spectromicroscopy: Insight in Early Biomineral Formation in Human Kidney.

Idiopathic kidney stones originate mainly from calcium phosphate deposits at the tip of renal papillae, known as Randall's plaques (RPs), also detected in most human kidneys without stones. However, little is known about the mechanisms involved in RP formation. The localization and characterization of such nano-sized objects in the kidney remains a real challenge making their study arduous. This study provides a nanoscale analysis of the chemical composition and morphology of incipient RPs, characterizing in particular the interface between the mineral and the surrounding organic compounds. Relying on data gathered from a calculi collection, the morphology and chemical composition of incipient calcifications in renal tissue was determined using spatially resolved electron energy-loss spectroscopy (EELS). We detected micro-calcifications and individual nano-calcifications found at some distance from the larger ones. Strikingly, concerning the smaller ones, we show that two types of nano-calcifications coexist: calcified organic vesicles and nanometric mineral granules mainly composed of calcium phosphate with carbonate in their core. Interestingly, some of these nano-calcifications present similarities with those reported in physiological bone or pathological cardiovascular biominerals, suggesting possible common formation mechanisms. However the high diversity of these nano-calcifications suggests that several mechanisms may be involved (nucleation on a carbonate core or on organic compounds). In addition, incipient RPs also appear to present specific features at larger scales revealing secondary calcified structures embedded in a fibrillar organic material. Our study proves that analogies exist between physiological and pathological biominerals and provides information to understand the physico-chemical processes involved in pathological calcification formation.