Cécile Verrier1, Dominique Bazin2, Léa Huguet3, Odile Stéphan4, Alexandre Gloter4, Marie-Christine Verpont3, Vincent Frochot5, Jean-Philippe Haymann6, Isabelle Brocheriou7, Olivier Traxer8, Michel Daudon6, Emmanuel Letavernier9. 1. 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. 2. 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. 3. Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S 1155, Paris, France. 4. Laboratoire de Physique des Solides, Centre National de la Recherche Scientifique Unités Mixtes de Recherche 8502, Université Paris Sud XI, Orsay, France. 5. Physiology Unit, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France. 6. 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. 7. 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. 8. 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. 9. 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.
Abstract
PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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: Benjamin A Sherer; Ling Chen; Misun Kang; Alex R Shimotake; Scott V Wiener; Tom Chi; Marshall L Stoller; Sunita P Ho Journal: Acta Biomater Date: 2018-02-09 Impact factor: 8.947
Authors: Joshua N Curry; Matthew Saurette; Masomeh Askari; Lei Pei; Michael B Filla; Megan R Beggs; Peter Sn Rowe; Timothy Fields; Andre J Sommer; Chizu Tanikawa; Yoichiro Kamatani; Andrew P Evan; Mehdi Totonchi; R Todd Alexander; Koichi Matsuda; Alan Sl Yu Journal: J Clin Invest Date: 2020-04-01 Impact factor: 14.808
Authors: Seth Winfree; Courtney Weiler; Sharon B Bledsoe; Tony Gardner; André J Sommer; Andrew P Evan; James E Lingeman; Amy E Krambeck; Elaine M Worcester; Tarek M El-Achkar; James C Williams Journal: Urolithiasis Date: 2020-10-07 Impact factor: 3.436