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Infrared (IR) spectromicroscopy allows chemical mapping of a kidney biopsy. It is particularly interesting for chemical speciation of abnormal tubular deposits and calcification. In 2017, using IR spectromicroscopy, we described a new entity called vancomycin cast nephropathy. However, despite recent progresses, the IR microspectrometer spatial resolution is intrinsically limited by diffraction (a few micrometers). Combining atomic force microscopy and IR lasers (AFMIR) allows acquisition of infrared absorption spectra with a resolution and sensitivity in between 10 and 100 nm. Here we show that AFMIR can be used on standard paraffin embedded kidney biopsies. Vancomycin cast could be identified in a damaged tubule. Interestingly unlike standard IR spectromicroscopy, AFMIR revealed heterogeneity of the deposits and established that vancomycin coprecipitated with phosphate containing molecules. These findings highlight the high potential of this approach with nanometric spatial resolution which opens new perspectives for studies on drug-induced nephritis, nanocrystals, and local lipid or carbohydrates alterations.

Whitlockite is a calcium phosphate phase of crucial interest in various pathologies. It appears in abnormal calcification such as dental calculi, kidney stones, or dystrophic calcifications of tuberculous origin. It is a complex material which involves cation substitutions, cation vacancies, and protonation of phosphate groups. In the literature, there is a lack of theoretical characterization of such materials originating from biological calcifications. By means of DFT calculations, we were able to quantify the ability of whitlockite to hold these substitutions and vacancies in preferential sites. The impact of Ca2+/Mg2+substitutions on characterizations (IR, RAMAN, and XRD) was also investigated in the scope of DFT.

Idiopathic kidney stones originate mainly from calcium phosphate deposits at the tip of renal papillae, known as Randall’s plaques (RPs), also detected in most human kidneys without stones. However, little is known about the mechanisms involved in RP formation. The localization and characterization of such nanosized objects in the kidney remain a real challenge, making their study arduous. This study provides a nanoscale analysis of the chemical composition and morphology of incipient RPs, characterizing in particular the interface between the mineral and the surrounding organic compounds. Relying on data gathered from a calculi collection, the morphology and chemical composition of incipient calcifications in renal tissue were determined using spatially resolved electron energy-loss spectroscopy. We detected microcalcifications and individual nanocalcifications found at some distance from the larger ones. Strikingly, concerning the smaller ones, we show that two types of nanocalcifications coexist: calcified organic vesicles and nanometric mineral granules mainly composed of calcium phosphate with carbonate in their core. Interestingly, some of these nanocalcifications present similarities with those reported in physiological bone or pathological cardiovascular biominerals, suggesting possible common formation mechanisms. However, the high diversity of these nanocalcifications suggests that several mechanisms may be involved (nucleation on a carbonate core or on organic compounds). In addition, incipient RPs also appear to present specific features at larger scales, revealing secondary calcified structures embedded in a fibrillar organic material. Our study proves that analogies exist between physiological and pathological biominerals and provides information to understand the physicochemical processes involved in pathological calcification formation.

Objectives: To characterize and compare in vitro the surfaces of ureteral stents(STENTS) before utilization.

Most kidney stones are made of calcium oxalate crystals. Randall's plaque, an apatite deposit at the tip of the renal papilla, is considered to at the origin of these stones. Hypercalciuria may promote Randall's plaque formation and growth. We analyzed whether long-term exposure of Abcc6−/−mice (a murine model of Randall's plaque) to vitamin D supplementation, with or without a calcium-rich diet, would accelerate the formation of Randall's plaque. Eight groups of mice (including Abcc6−/−and wild type) received vitamin D alone (100,000 UI/kg every 2 weeks), a calcium-enriched diet alone (calcium gluconate 2 g/L in drinking water), both vitamin D supplementation and a calcium-rich diet, or a standard diet (controls) for 6 months. Kidney calcifications were assessed by 3-dimensional microcomputed tomography, μ-Fourier transform infrared spectroscopy, field emission-scanning electron microscopy, transmission electron microscopy, and Yasue staining. At 6 months, Abcc6−/−mice exposed to vitamin D and calcium supplementation developed massive Randall's plaque when compared with control Abcc6−/−mice (P < 0.01). Wild-type animals did not develop significant calcifications when exposed to vitamin D. Combined administration of vitamin D and calcium significantly accelerates Randall's plaque formation in a murine model. This original model raises concerns about the cumulative risk of vitamin D supplementation and calcium intakes in Randall's plaque formation.

With the aim of rationalizing the reactivity of transition-metal (TM) clusters, the model reaction of NO dissociation on TM13clusters was investigated on a set of seven TMs. The adsorption energy and the activation energy for NO dissociation were calculated for each TM and discussed within the findings of Boudart in his article “model catalysts: reductionism for understanding”. In this work, we focused on selected TM cluster calculations instead of surface science slab-type calculations, which have been performed for some TMs and focus on the electronic structure to investigate and rationalize the TM reactivity. Besides the electronic and spin properties of the TM, we discuss the reactivity trends using also qualitatively the chemical hardness and softness. We conclude that the combination of these reactivity parameters will be necessary to fine-tune TM clusters’ reactivity with the scope of multimetallic TM clusters.

IMPORTANCE: Calcific uremic arteriolopathy (CUA), a rare, potentially fatal, disease with calcium deposits in skin, mostly affects patients with end-stage renal disease who are receiving dialysis. Chemical composition and structure of CUA calcifications have been poorly described. OBJECTIVES: To describe the localization and morphologic features and determine the precise chemical composition of CUA-related calcium deposits in skin, and identify any mortality-associated factors. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, multicenter cohort study was conducted at 7 French hospitals including consecutive adults diagnosed with CUA between January 1, 2006, and January 1, 2017, confirmed according to Hayashi clinical and histologic criteria. Patients with normal renal function were excluded. For comparison, 5 skin samples from patients with arteriolosclerosis and 5 others from the negative margins of skin-carcinoma resection specimens were also analyzed. MAIN OUTCOMES AND MEASURES: Localization and morphologic features of the CUA-related cutaneous calcium deposits were assessed with optical microscopy and field-emission–scanning electron microscopy, and the chemical compositions of those deposits were evaluated with μ Fourier transform infrared spectroscopy, Raman spectroscopy, and energy dispersive radiographs. RESULTS: Thirty-six patients (median [range] age, 64 [33-89] years; 26 [72%] female) were included, and 29 cutaneous biopsies were analyzed. Calcific uremic arteriolopathy and arteriolosclerosis skin calcifications were composed of pure calcium–phosphate apatite. Calcific uremic arteriolopathy vascular calcifications were always circumferential, found in small to medium-sized vessels, with interstitial deposits in 22 (76%) of the samples. A thrombosis, most often in noncalcified capillary lumens in the superficial dermis, was seen in 5 samples from patients with CUA. Except for calcium deposits, the vessel structure of patients with CUA appeared normal, unlike thickened arteriolosclerotic vessel walls. Twelve (33%) patients died of CUA. CONCLUSIONS AND RELEVANCE: Calcific uremic arteriolopathy–related skin calcifications were exclusively composed of pure calcium–phosphate apatite, localized circumferentially in small to medium-sized vessels and often associated with interstitial deposits, suggesting its pathogenesis differs from that of arteriolosclerosis. Although the chemical compositions of CUA and arteriolosclerosis calcifications were similar, the vessels’ appearances and deposit localizations differed, suggesting different pathogenetic mechanisms.

Vitamin D supplementation in humans should be accompanied by calcium administration to avoid bone demineralization through vitamin D receptor signaling. Here we analyzed whether long-term exposure of rats to vitamin D supplementation, with or without a calcium-rich diet, would promote kidney stone formation. Four groups of rats received vitamin D alone (100,000 UI/kg/3 weeks), a calcium-enriched diet alone, both vitamin D supplementation and calcium-enriched diet, or a standard diet (controls) for 6 months. Serum and urine parameters and crystalluria were monitored. Kidney stones were assessed by 3-dimensional micro-computed tomography, infrared spectroscopy, von Kossa/Yasue staining, and field emission scanning electron microscopy. Although serum calcium levels were similar in the 4 groups, rats receiving vitamin D had a progressive increase in urinary calcium excretion over time, especially those receiving both calcium and vitamin D. However, oral calcium supplementation alone did not increase urinary calcium excretion. At 6 months, rats exposed to both calcium and vitamin D, but not rats exposed to calcium or vitamin D alone, developed significant apatite kidney calcifications (mean volume, 0.121 mm3). Thus, coadministration of vitamin D and increased calcium intake had a synergistic role in tubular calcifications or kidney stone formation in this rat model. Hence, one should be cautious about the cumulative risk of kidney stone formation in humans when exposed to both vitamin D supplementation and high calcium intake.

La calciphylaxie urémique est une maladie grave qui survient généralement chez les patients insuffisants rénaux dialysés présentant un produit phosphocalcique élevé. Comme dans d’autres dermatoses calcifiantes, les dépôts calciques, composés d’hydroxyapatite, ont un tropisme vis-à-vis des fibres élastiques du derme et de la limitante élastique des vaisseaux. L’objectif de notre étude était de caractériser par microscopie multiphoton (MM) les altérations structurelles des fibres élastiques et des calcifications cutanées au cours de la calciphylaxie.

Plasma urate levels are higher in humans than rodents (240–360 vs. ∼30 μM) because humans lack the liver enzyme uricase. High uricemia in humans may protect against oxidative stress, but hyperuricemia also associates with the metabolic syndrome, and urate and uric acid can crystallize to cause gout and renal dysfunctions. Thus, hyperuricemic animal models to study urate-induced pathologies are needed. We recently generated mice with liver-specific ablation of Glut9, a urate transporter providing access of urate to uricase (LG9KO mice). LG9KO mice had moderately high uricemia (∼120 μM). To further increase their uricemia, here we gavaged LG9KO mice for 3 days with inosine, a urate precursor; this treatment was applied in both chow- and high-fat-fed mice. In chow-fed LG9KO mice, uricemia peaked at 300 μM 2 h after the first gavage and normalized 24 h after the last gavage. In contrast, in high-fat-fed LG9KO mice, uricemia further rose to 500 μM. Plasma creatinine strongly increased, indicating acute renal failure. Kidneys showed tubule dilation, macrophage infiltration, and urate and uric acid crystals, associated with a more acidic urine. Six weeks after inosine gavage, plasma urate and creatinine had normalized. However, renal inflammation, fibrosis, and organ remodeling had developed despite the disappearance of urate and uric acid crystals. Thus, hyperuricemia and high-fat diet feeding combined to induce acute renal failure. Furthermore, a sterile inflammation caused by the initial crystal-induced lesions developed despite the disappearance of urate and uric acid crystals.

Dans la nécrolyse épidermique toxique (NET), la cicatrisation commence vers le 8ejour et se poursuit sur 2 à 3 semaines. Nous décrivons trois patients admis en réanimation pour NET, et dont l’évolution était caractérisée par des troubles de cicatrisation avec calcifications dermiques pour lesquels nous avons évoqué la responsabilité de la caspofungine, utilisée dans les infections fongiques invasives.

The recent discovery (1967) of a «porphyry copper» deposit in the Tertiary volcano-sedimentary complex of the Kerman region has encouraged detailed prospecting in this relatively unexplored region. This complex extends intermittently from Turkey to Baluchistan with a general south-easterly trend and with relatively uniform character. South of Kerman it is bordered by the metamorphic basement of Sirjan. The complex is folded in an east-west direction and is intersected by a system of north-south echelon faults along which dykes have been intruded. This network of fractures conforms with the «Oman high» which limits the basement and the copper mineralizations to the east and particularly seems to represent a paleogeographic limit. The Paleogene lavas, pyroclastics and sediments are cut by Neogene subvolcanic intrusions. Dykes, sills, and stocks of porphyritic granodiorite invade the cores and flanks of anticlines. Copper mineralization occurs mainly as disseminations around and in the altered stocks, and in the form of veins and stockworks and as impregnations in the surrounding lavas and pyroclastic rocks. Other regions in Iran showing copper mineralizations associated with the Tertiary volcanosedimentary complex have been studied in less detail than the Kerman region. The distribution of the deposits seems to depend upon paleogeographic and structural conditions.

Calcium-containing (CaC) crystals, including basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP), are associated with destructive forms of osteoarthritis (OA). We assessed their distribution and biochemical and morphologic features in human knee OA cartilage.

The structural information found using three techniques related to synchrotron radiation are compared. XAS (X-ray Absorption Spectroscopy), AWAXS (Anomalous Wide Angle X-ray Scattering) and DAFS (Diffraction Anomalous Fine Structure) are applied to nanometer scale metallic clusters.

The structural information obtained using three techniques related to synchrotron radiation are compared. XAS (X-ray Absorption Spectroscopy), AWAXS (Anomalous Wide Angle X-ray Scattering) and DAFS (Diffraction Anomalous Fine Structure) are applied to the study of nanometer scale bimetallic clusters.