Correspondence
Peculiar Morphology of Stones in Primary Hyperoxaluria
N Engl J Med 2008; 359:100-102July 3, 2008
- Article
To the Editor:
Primary hyperoxaluria type 1 is a rare inherited disease leading to recurrent nephrolithiasis, nephrocalcinosis, systemic oxalosis, and renal failure, ultimately requiring combined kidney and liver transplantation.1,2 Because of the rarity of this disorder, the diagnosis is often missed or delayed by several years, especially when the disease first manifests in adulthood, thus depriving patients of the benefits of therapeutic measures that have been instituted in a timely manner.2,3 Therefore, any method allowing early diagnosis is eagerly awaited.4 However, although nephrolithiasis is the revealing symptom in the great majority of patients with this disease at any age, until now little attention has been paid to the analysis of stones as a possible diagnostic tool.
Over the past 20 years, we analyzed stones obtained from 74 patients with a diagnosis of primary hyperoxaluria type 1 established on the basis of complete urinary biochemical tests and evidence of an enzyme defect. In addition to findings on infrared spectroscopy, we examined the morphologic characteristics of the surface and sections of calculi by means of a stereomicroscope.5 All primary hyperoxaluria type 1 calculi were composed of pure or virtually pure (>95%) calcium oxalate monohydrate, or whewellite. As compared with idiopathic calcium stones with a similarly high whewellite content, all primary hyperoxaluria type 1 calculi showed very peculiar morphologic characteristics, including a whitish or pale-yellow surface and a loose, unorganized section, quite different from the dark-brown surface and well-organized, radiating inner structure of common whewellite stones (Figure 1Figure 1
Morphologic Characteristics of a Whewellite Stone in Typical Primary Hyperoxaluria Type 1 and of a Typical, Idiopathic, Common Type of Whewellite Stone.). In addition, scanning electron microscopy confirmed a crystalline structure in the primary hyperoxaluria type 1 stone that was distinct from that of the common type of whewellite stone. This unique morphologic characteristic and the ultrastructure of primary hyperoxaluria type 1 stones suggest a fundamental difference in the mechanism of stone formation, reflecting the very rapid and permanent crystal formation induced by genetic hyperoxaluria. The peculiar morphologic characteristics of stones consistently observed in patients with primary hyperoxaluria type 1 (and in the two patients with primary hyperoxaluria type 2 whose stones were analyzed at our laboratory) appeared to be pathognomonic for this cause, since it was never observed in patients with other hyperoxaluric states (including 45 patients with enteric hyperoxaluria) or in any patient in whom a calcium stone formed without hyperoxaluria. Therefore, such appearance of stones might be a valuable indicator of primary hyperoxaluria type 1, prompting early comprehensive laboratory evaluation, including measurements of urinary oxalate, glycolate, and glycerate in order to achieve a definitive diagnosis.On the basis of our positive clinical experience, we propose that a morphologic examination be performed before compositional analysis by means of x-ray diffraction or infrared spectroscopy, since this direct examination constitutes a simple, rapid, and cheap tool that might point toward the early diagnosis of primary hyperoxaluria type 1. This diagnosis might provide affected patients with a better chance to benefit from the early institution of adequate therapeutic management and might prevent, or substantially retard, the consequences of this devastating disease.
Michel Daudon, Ph.D.
Paul Jungers, M.D.
Necker Hospital, 75015 Paris, France
michel.daudon@nck. aphp. fr Dominique Bazin, Ph.D.
Paris-Sud University, 91405 Orsay, FranceSupported by the Centre National de la Recherche Scientifique and Paris-Sud University.
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- Citing Articles (12)
Citing Articles
1
A. Dessombz, P. Méria, D. Bazin, E. Foy, S. Rouzière, R. Weil, M. Daudon. (2011) Diversité chimique des calculs prostatiques : une investigation par MEB et spectroscopie infrarouge. Progrès en Urologie 21:13, 940-945
CrossRef2
Dominique Bazin, Gilles André, Raphael Weil, Guy Matzen, Veron Emmanuel, Xavier Carpentier, M. Daudon. (2011) Absence of Bacterial Imprints on Struvite-containing Kidney Stones: A Structural Investigation at the Mesoscopic and Atomic Scale. Urology
CrossRef3
D. Bazin, M. Daudon, Ch. Chappard, J. J. Rehr, D. Thiaudière, S. Reguer. (2011) The status of strontium in biological apatites: an XANES investigation. Journal of Synchrotron Radiation 18:6, 912-918
CrossRef4
Zhiqiang Chen, Guanlin Liu, Zhangqun Ye, Debo Kong, Lingfang Yao, Hui Guo, Weimin Yang, Xiao Yu. (2011) The construction of an oxalate-degrading intestinal stem cell population in mice: a potential new treatment option for patients with calcium oxalate calculus. Urological Research
CrossRef5
K. Bouchireb, O. Boyer, C. Pietrement, H. Nivet, H. Martelli, O. Dunand, F. Nobili, G. L. Sylvie, P. Niaudet, R. Salomon, M. Daudon. (2011) Papillary stones with Randall's plaques in children: clinicobiological features and outcome. Nephrology Dialysis Transplantation
CrossRef6
Jozef Kaiser, Markéta Holá, Michaela Galiová, Karel Novotný, Viktor Kanický, Petr Martinec, Jiří Ščučka, Francesco Brun, Nicola Sodini, Giuliana Tromba, Lucia Mancini, Tamara Kořistková. (2011) Investigation of the microstructure and mineralogical composition of urinary calculi fragments by synchrotron radiation X-ray microtomography: a feasibility study. Urological Research 39:4, 259-267
CrossRef7
Xavier Carpentier, Dominique Bazin, Christelle Combes, Aurélie Mazouyes, Stephan Rouzière, Pierre Antoine Albouy, Eddy Foy, Michel Daudon. (2011) High Zn content of Randall's plaque: A μ-X-ray fluorescence investigation. Journal of Trace Elements in Medicine and Biology 25:3, 160-165
CrossRef8
Xavier Carpentier, Dominique Bazin, Paul Jungers, Solenn Reguer, Dominique Thiaudière, Michel Daudon. (2010) The pathogenesis of Randall's plaque: a papilla cartography of Ca compounds through an ex vivo investigation based on XANES spectroscopy. Journal of Synchrotron Radiation 17:3, 374-379
CrossRef9
Jérôme Harambat, Sonia Fargue, Cécile Acquaviva, Marie-France Gagnadoux, Françoise Janssen, Aurélia Liutkus, Chebl Mourani, Marie-Alice Macher, Daniel Abramowicz, Christophe Legendre, Antoine Durrbach, Michel Tsimaratos, Hubert Nivet, Eric Girardin, Anne-Marie Schott, Marie-Odile Rolland, Pierre Cochat. (2010) Genotype–phenotype correlation in primary hyperoxaluria type 1: the p.Gly170Arg AGXT mutation is associated with a better outcome. Kidney International 77:5, 443-449
CrossRef10
Marcin Słojewski, Bogusław Czerny, Krzysztof Safranow, Marek Droździk, Andrzej Pawlik, Katarzyna Jakubowska, Maria Olszewska, Adam Gołąb, Elżbieta Byra, Dariusz Chlubek, Andrzej Sikorski. (2009) Does smoking have any effect on urinary stone composition and the distribution of trace elements in urine and stones?. Urological Research 37:6, 317-322
CrossRef11
(2009) Leaving No Stone Unturned. BJU International 104:8, ii-v
CrossRef12
Daudon, Michel, Jungers, Paul, , Bazin, Dominique, . (2009) Stones in Primary Hyperoxaluria — A Clarification. New England Journal of Medicine 360:16, 1680-1680
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