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

Abstract

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 nanocalcifications coexist: calcified organic vesicles and nanometric mineral granules mainly composed of calcium phosphate with carbonate in their core. Interestingly, some of these nanocalcifications 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.

Osteogenic Differentiation of Renal Interstitial Fibroblasts Promoted by lncRNA MALAT1 May Partially Contribute to Randall’s Plaque Formation

“…Additionally, upregulation of osteogenesis-specific genes in the renal interstitium was identified in rats with hyperoxaluria induced by hydroxy-Lproline (Joshi et al, 2015). Moreover, in a recent study, nanoscale analysis of incipient RP was performed through electron energy loss spectrometry (Gay et al, 2020) and this study showed that some nanocalcifications exhibited similarities with physiological bone or cardiovascular pathological calcifications. In the current study, we similarly discovered The protein expression level of Runx2 was confirmed by WB in hRIFs treated with the miR-320a-5p mimic or miR-320a-5p inhibitor.…”

Bone Mineral Analogue Ceramic Block as an Instant Adhesive to Biological Soft Tissue

“…Furthermore, this model can be adapted to formation processes of other hard tissues composed of calcium phosphate and organic matters, such as Randall's plaques of urinary stones. [ 27 ]…”

“…Furthermore, this model can be adapted to formation processes of other hard tissues composed of calcium phosphate and organic matters, such as Randall's plaques of urinary stones. [27] The demand and number of implantable devices is growing each year. Although tight attachment to tissues is an essential property of implantable devices such as heart pacemakers, a number of devices (such as external fixation pins) must be safely removed after serving their clinical purpose.…”

Multiple Pathways for Pathological Calcification in the Human Body

“…Interestingly, a similar juxtaposition of collagen fibrils and mineral deposits has been described for early stages of kidney stone formation. [ 259 ] Finally, in many cases there is no fibrillar collagen in contact with the mineral, as in the example shown within a case of low‐grade ductal carcinoma in situ (DCIS) (Figure 3k–n). Note that as we discuss additional examples of pathological mineralization (Section 3.3), we will see additional examples of a range of collagen–mineral interactions.…”