Topography, composition and structure of incipient Randall’s plaque at the nanoscale level

International audiencePurposeAlexander Randall identified calcium phosphate plaques in renal papillae as the origin of kidney stones. However, little is known about the early steps of Randall’s plaque formation, preceding the onset of urolithiasis. Our objectives were to characterize the composition and the initial formation site of incipient Randall’s plaque in non-stone formers living patients.Material and MethodsMedian age of the patients was 67.7 years. Fifty-four healthy papillae from kidneys removed for cancer and without stones have been analyzed by immunohistochemistry and Von Kossa staining, Field Emission-Scanning Electron Microscopy with Energy Dispersive X-ray analysis, μ-Fourier Transform Infrared Spectroscopy, Cryo-Transmission Electron Microscopy coupled to Selected-Area Electron Diffraction and Electron Energy Loss Spectroscopy.ResultsIncipient Randall’s plaque has been observed in 72.7% of kidneys. Carbonated apatite was as expected the main component of microcalcifications but amorphous calcium phosphate and whitlockite have been identified in 80% and 40% of the papillae, respectively. Incipient plaques stood in the deepest part of the papillae, around the loop of Henle tip but also around vasa recta (respectively 62.4 % and 37.2 % of microcalcifications) and rarely close to collecting ducts. At the nanoscale level, incipient calcifications were often made of several nanocrystals inside organic material looking like microvesicles.ConclusionsIncipient Randall’s plaque is frequent and appears at the extreme tip of renal papillae, around the hairpin structure of the loop of Henle but also around vasa recta. Nanoscale analyses suggest a local nucleation process promoting nanocrystal growth in a supersaturated milieu. In addition, plaques contain various calcium and magnesium phosphates and not only carbonated apatite