Xavier Carpentier

Relationships Between Carbonation Rate of Carbapatite and Morphologic Characteristics of Calcium Phosphate Stones and Etiology

OBJECTIVES To examine the significance of the carbonation rate (CR) in carbonated apatite (carbapatite [CA]) stones and its relationships with the morphologic characteristics of CA and etiology. CA stones without struvite can result from metabolic disorders or urinary tract infection, but the latter etiology is still debated. Infection stones caused by urea-splitting bacteria are made of CA admixed with struvite and exhibit a high CO(3)(2-)/PO(4)(3-) ratio (CR). However, little is known as to the significance of the CR of CA in the absence of struvite in idiopathic calcium phosphate stones. METHODS We studied 39 urinary calculi mainly composed of CA without struvite. Of the 39 patients, 13 had a past or present history of urinary tract infection, 24 had hypercalciuria, and 2 had medullary sponge kidney. The stones were examined by Fourier transform infrared spectroscopy and scanning electron microscopy. The presence of amorphous carbonated calcium phosphate or whitlockite was also considered. RESULTS The CR of CA was 14% +/- 9%. On scanning electron microscopy, the CA particles appeared as spherules of 4.5 +/- 3.0 mum in diameter and were significantly larger in females than in males. In 16 cases, scanning electron microscopy showed bacterial imprints. In these calculi, the CR was significantly greater (22% +/- 7%) than in those without a visible bacterial imprint (8% +/- 5%, P < .0001). Amorphous carbonated calcium phosphate was found in 15 of 16 stones (93.8%) with imprints and in none of the 23 stones without imprints (P < .0001). CONCLUSIONS A close relationship was observed between the presence of bacterial imprints, indicative of past or current urinary tract infection, and both the presence of amorphous carbonated calcium phosphate (or whitlockite) and a high CR of CA.

Diffraction techniques and Vibrational spectroscopy opportunities to characterise bones

From a histological point of view, bones that allow body mobility and protection of internal organs consist not only of different organic and inorganic tissues but include vascular and nervous elements as well. Moreover, due to its ability to host different ions and cations, its mineral part represents an important reservoir, playing a key role in the metabolic activity of the organism. From a structural point of view, bones can be considered as a composite material displaying a hierarchical structure at different scales. At the nanometre scale, an organic part, i.e. collagen fibrils and an inorganic part, i.e. calcium phosphate nanocrystals are intimately mixed to assure particular mechanical properties.

Revisiting the localisation of Zn2+ cations sorbed on pathological apatite calcifications made through X-ray absorption spectroscopy

The role of oligo-elements such as Zn in the genesis of pathological calcifications is widely debated in the literature. An essential element of discussion is given by their localisation either at the surface or within the Ca apatite crystalline network. To determine the localisation, X-ray absorption experiments have been performed at SOLEIL. The Exafs results suggest that Zn atoms, present in the Zn(2+) form, are bound to about 4 O atoms at a distance of 2.00 A, while the interatomic distance R(CaO) ranges between 2.35 A and 2.71 A. Taking into account the content of Zn (around 1000 ppm) and the difference in ionic radius between Zn(2+) (0.074 nm) and Ca(2+) (0.099 nm), a significant longer interatomic distance would be expected in the case of Zn replacing Ca within the apatite crystalline network. We thus conclude that Zn atoms are localised at the surface and not in the apatite nanocrystal structure. Such structural result has essential biological implications for at least two reasons. Some oligoelements have a marked effect on the transformation of chemical phases, and may modify the morphology of crystals. These are both major issues because, in the case of kidney stones, the medical treatment depends strongly on the precise chemical phase and on the morphology of the biological entities at both macroscopic and mesoscopic scales.

High Zn content of Randall's plaque: A μ-X-ray fluorescence investigation

Kidney stone disease, or nephrolithiasis, is a common ailment. Among the different risk factors usually associated with nephrolithiasis are dehydration, metabolic defects (especially with regard to calcium and oxalate). The presence of a mineral deposit at the surface of the renal papilla (termed Randalls plaque) has all been recently underlined. Of note, Randalls plaque is made of the calcium phosphate, carbapatite, and serves as a nucleus for kidney stone formation. The process by which apatite nanocrystals nucleate and form Randalls plaque remains unclear. This paper deals with the possible relationship between trace elements and the formation of this mineral. The investigation has been performed on a set of Randalls plaques, extracted from human kidney stones, through μ-X-ray diffraction and μ-X-ray fluorescence analyses in order to determine the chemical composition of the plaque as well as the nature and the amount of trace elements. Our data provide evidence that Zn levels are dramatically increased in carbapatite of RP by comparison to carbapatite in kidney stones, suggesting that calcified deposits within the medullar interstitium are a pathological process involving a tissue reaction. Further studies, perhaps including the investigation of biomarkers for inflammation, are necessary for clarifying the role of Zn in Randalls plaque formation.

Absence of Bacterial Imprints on Struvite-containing Kidney Stones: A Structural Investigation at the Mesoscopic and Atomic Scale

OBJECTIVE Bacterial imprints are always observed on highly carbonated apatite kidney stones but not struvite kidney stones. Struvite and carbonated apatite stones with a high CO(3)(2-)/PO(4)(3-) rate are believed to develop from infections, but their structural differences at the mesoscopic scale lack explanation. METHODS We investigated 17 urinary calculi composed mainly of struvite or carbonated apatite by Fourier transform infrared, scanning electron microscopy, and powder neutron diffraction techniques. RESULTS Carbonated apatite but not struvite stones showed bacterial imprints. If the same stone contained both carbonated apatite and struvite components, bacterial imprints were observed on the carbonated apatite but not the struvite part. Moreover, neutron powder diffraction experiments revealed the crystal size of struvite stones were larger than that of carbonated apatite stones (250 ± 50 vs 50 nm). CONCLUSION Bacterial imprints may appear more easily on kidney stones with small nanocrystals, such as carbonated apatite than with large nanocrystals, such as struvite. This approach may help identify bacteria contributing to stone formation, perhaps with negative results of urine culture.

The pathogenesis of Randall's plaque: a papilla cartography of Ca compounds through an ex vivo investigation based on XANES spectroscopy.

At the surface of attached kidney stones, a particular deposit termed Randalls plaque (RP) serves as a nucleus. This structural particularity as well as other major public health problems such as diabetes type-2 may explain the dramatic increase in urolithiasis now affecting up to 20% of the population in the industrialized countries. Regarding the chemical composition, even if other phosphate phases such as whitlockite or brushite can be found as minor components (less than 5%), calcium phosphate apatite as well as amorphous carbonated calcium phosphate (ACCP) are the major components of most RPs. Through X-ray absorption spectroscopy performed at the Ca K-absorption edge, a technique specific to synchrotron radiation, the presence and crystallinity of the Ca phosphate phases present in RP were determined ex vivo. The sensitivity of the technique was used as well as the fact that the measurements can be performed directly on the papilla. The sample was stored in formol. Moreover, a first mapping of the chemical phase from the top of the papilla to the deep medulla is obtained. Direct structural evidence of the presence of ACCP as a major constituent is given for the first time. This set of data, coherent with previous studies, shows that this chemical phase can be considered as one precursor in the genesis of RP.

Very first tests on SOLEIL regarding the Zn environment in pathological calcifications made of apatite determined by X-ray absorption spectroscopy

This very first report of an X-ray absorption spectroscopy experiment at Synchrotron SOLEIL is part of a long-term study dedicated to pathological calcifications. Such biological entities composed of various inorganic and/or organic compounds also contain trace elements. In the case of urinary calculi, different papers already published have pointed out that these oligo-elements may promote or inhibit crystal nucleation as well as growth of mineral. Use of this analytical tool specific to synchrotron radiation, allowing the determination of the local environment of oligo-elements and thus their occupation site, contributes to the understanding of the role of trace elements in pathological calcifications.

Dismantling papillary renal cell carcinoma classification: The heterogeneity of genetic profiles suggests several independent diseases.

Papillary renal cell carcinoma (pRCC) is the second most frequent renal cell carcinoma (RCC) after clear cell RCC. In contrast to clear cell RCC, there is no consensual protocol using targeted therapy for metastatic pRCC. Moreover, diagnosis of some pRCC, especially pRCC of type 2 (pRCC2) may be challenging. Our aim was to identify molecular biomarkers that could be helpful for the diagnosis and treatment of pRCC. We studied the clinical, histological, immunohistological, and comprehensive genetic features of a series of 31 pRCC including 15 pRCC1 and 16 pRCC2. We aimed to determine whether pRCC represents a unique entity or several diseases. In addition, we compared the genetic features of pRCC2 to those of eight RCC showing various degrees of tubulo‐papillary architecture, including three TFE‐translocation RCC and five unclassified RCC. We demonstrate that pRCC is a heterogeneous group of tumors with distinct evolution. While most pRCC2 had genetic profiles similar to pRCC1, some shared genomic features, such as loss of 3p and loss of chromosome 14, with clear cell RCC, TFE‐translocation RCC, and unclassified RCC. We identified variants of the MET gene in three pRCC1. A mutation in the BRAF gene was also identified in one pRCC1. In addition, using next‐generation sequencing (NGS), we identified several variant genes. Genomic profiling completed by NGS allowed us to classify pRCC2 in several groups and to identify novel mutations. Our findings provide novel information on the pathogenesis of pRCC that allow insights for personalized treatment.

A report of unusual crossed fused renal ectopia and minimal invasive management of calculi

Crossed renal ectopias with fusion are rare anomalies of the kidney. Urinary upper tract anatomy is modified and urinary stones may occur. We report such a case, with precise anatomical description of the kidneys and the successful management of a stone with minimal invasive techniques.