title: Topography, Composition and Structure of Incipient Randall Plaque at the Nanoscale Level.
abstract: Randall identified calcium phosphate plaques in renal papillae as the origin of kidney stones. However, little is known about the early steps of Randall plaque formation preceding the onset of urolithiasis. Our objective was to characterize the composition and the initial formation site of incipient Randall plaque in nonstone forming, living patients.
  
  
  
  Median patient age was 67.7 years. A total of 54 healthy papillae from kidneys removed for cancer and without stones were 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.
  
  
  
  Incipient Randall plaque was observed in 72.7% of kidneys. As expected, carbonated apatite was the main component of microcalcifications but amorphous calcium phosphate and whitlockite were identified in 80% and 40% of papillae, respectively. Incipient plaques were noted in the deepest part of the papillae around the loop of Henle tip as well as around the vasa recta, representing 62.4% and 37.2% of microcalcifications, respectively. Plaques were rarely close to collecting ducts. At the nanoscale level incipient calcifications were often composed of several nanocrystals in organic material that looked like microvesicles.
  
  
  
  Incipient Randall plaque is frequent. It appears not only at the extreme tip of the renal papillae around the hairpin structure of the loop of Henle but also around the 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S 1155, Paris, France; Urology Unit, Assistance Publique Hôpitaux de Paris, Hôpital Saint-Louis, Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Verrier
authors.affiliation: Centre National de la Recherche Scientifique, Laboratoire de Chimie de la Matière Condensée de Paris, Université Pierre et Marie Curie, Collège de France, Paris, France; Laboratoire de Physique des Solides, Centre National de la Recherche Scientifique Unités Mixtes de Recherche 8502, Université Paris Sud XI, Orsay, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bazin
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S 1155, Paris, France.
authors.forename: Léa
authors.initials: L
authors.lastname: Huguet
authors.affiliation: Laboratoire de Physique des Solides, Centre National de la Recherche Scientifique Unités Mixtes de Recherche 8502, Université Paris Sud XI, Orsay, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Stéphan
authors.affiliation: Laboratoire de Physique des Solides, Centre National de la Recherche Scientifique Unités Mixtes de Recherche 8502, Université Paris Sud XI, Orsay, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Gloter
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S 1155, Paris, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Verpont
authors.affiliation: Physiology Unit, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Frochot
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S 1155, Paris, France; Physiology Unit, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Haymann
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S 1155, Paris, France; Pathology Unit, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Brocheriou
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 06, Unité Mixte de Recherche S 1155, Paris, France; Urology Unit, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Traxer
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S 1155, Paris, France; Physiology Unit, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Daudon
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S 1155, Paris, France; Physiology Unit, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France. Electronic address: emmanuel.letavernier@tnn.aphp.fr.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Letavernier
mesh_terms: D000368:Aged; D002114:Calcinosis / Q000473:pathology*; D003460:Crystallization; D006801:Humans; D007674:Kidney Diseases / Q000473:pathology*; D007679:Kidney Medulla / Q000737:chemistry / Q000473:pathology*; D008855:Microscopy, Electron, Scanning; D010710:Phosphates / Q000032:analysis
chemical_list: D010710:Phosphates
keywords: calcinosis; calcium phosphate; kidney medulla; nanoparticles; nephrolithiasis