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Previous Volume 359:100-102 July 3, 2008 Number 1 Next

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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 1). 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.

View larger version (79K): [in this window] [in a new window]   Figure 1. Morphologic Characteristics of a Whewellite Stone in Typical Primary Hyperoxaluria Type 1 and of a Typical, Idiopathic, Common Type of Whewellite Stone. Panels A, B, and C show a typical whewellite stone from a patient with primary hyperoxaluria type 1. Panels D, E, and F show a typical, idiopathic, common type of whewellite stone. Panels A and D show the stone surfaces on stereomicroscopic examination. Panels B and E show the sections on stereomicroscopic examination, and Panels C and F show the sections on scanning electron microscopy. There is a marked difference between the dense, radiating charcoal-like structure of the common type of stone, and the inhomogeneous, loose structure of the primary hyperoxaluria type 1 stone, with crystal aggregates of various sizes and shapes including curious, characteristic spherical structures of about 50 µm in diameter resembling balls of wool.

 
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{at}nck.aphp.fr

Dominique Bazin, Ph.D.
Paris-Sud University
91405 Orsay, France

Supported by the Centre National de la Recherche Scientifique and Paris-Sud University.

References

1. Cochat P. Primary hyperoxaluria type 1. Kidney Int 1999;55:2533-2547. [CrossRef][Web of Science][Medline]
2. Leumann E, Hoppe B. The primary hyperoxalurias. J Am Soc Nephrol 2001;12:1986-1993. [Free Full Text]
3. Hoppe B, Leumann E. Diagnostic and therapeutic strategies in hyperoxaluria: a plea for early intervention. Nephrol Dial Transplant 2004;19:39-42. [Free Full Text]
4. Lieske JC, Monico CG, Holmes WS, et al. International registry for primary hyperoxaluria. Am J Nephrol 2005;25:290-296. [CrossRef][Web of Science][Medline]
5. Daudon M, Bader CA, Jungers P. Urinary calculi: review of classification methods and correlations with etiology. Scanning Microsc 1993;7:1081-1104. [Web of Science][Medline]

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Related Letters:

Stones in Primary Hyperoxaluria — A Clarification
Daudon M., Jungers P., Bazin D.
Extract | Full Text | PDF  
N Engl J Med 2009; 360:1680, Apr 16, 2009. Correspondence

This article has been cited by other articles:

• Daudon, M., Jungers, P., Bazin, D. (2009). Stones in Primary Hyperoxaluria -- A Clarification. NEJM 360: 1680-1680 [Full Text]