Internalization of calcium oxalate crystals by renal tubular cells: A nephron segment–specific process?

Schepers, Marieke S.J.; Duim, Ronald A.J.; Asselman, Marino; Romijn, Johannes C.; Schröder, Fritz H.; Verkoelen, Carl F.

doi:10.1046/j.1523-1755.2003.00107.x

Cited by 60 publications

(49 citation statements)

References 29 publications

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“…The treatment time of 6 hours in this study is consistent with that described in previous studies on kidney stones. 22,23 We selected the concentrations of H 2 O 2 and crystals based on the following reasons. The commonly used H 2 O 2 concentration to induce cell injury ranged from 10 to 1,000 μmol/L.…”

Section: Cell Culturementioning

confidence: 99%

Reinjury risk of nano-calcium oxalate monohydrate and calcium oxalate dihydrate crystals on injured renal epithelial cells: aggravation of crystal adhesion and aggregation

Gan¹,

Sun²,

Bhadja³

et al. 2016

IJN

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Background Renal epithelial cell injury facilitates crystal adhesion to cell surface and serves as a key step in renal stone formation. However, the effects of cell injury on the adhesion of nano-calcium oxalate crystals and the nano-crystal-induced reinjury risk of injured cells remain unclear. Methods African green monkey renal epithelial (Vero) cells were injured with H 2 O 2 to establish a cell injury model. Cell viability, superoxide dismutase (SOD) activity, malonaldehyde (MDA) content, propidium iodide staining, hematoxylin–eosin staining, reactive oxygen species production, and mitochondrial membrane potential (Δψm) were determined to examine cell injury during adhesion. Changes in the surface structure of H 2 O 2 -injured cells were assessed through atomic force microscopy. The altered expression of hyaluronan during adhesion was examined through laser scanning confocal microscopy. The adhesion of nano-calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) crystals to Vero cells was observed through scanning electron microscopy. Nano-COM and COD binding was quantitatively determined through inductively coupled plasma emission spectrometry. Results The expression of hyaluronan on the cell surface was increased during wound healing because of Vero cell injury. The structure and function of the cell membrane were also altered by cell injury; thus, nano-crystal adhesion occurred. The ability of nano-COM to adhere to the injured Vero cells was higher than that of nano-COD crystals. The cell viability, SOD activity, and Δψm decreased when nano-crystals attached to the cell surface. By contrast, the MDA content, reactive oxygen species production, and cell death rate increased. Conclusion Cell injury contributes to crystal adhesion to Vero cell surface. The attached nano-COM and COD crystals can aggravate Vero cell injury. As a consequence, crystal adhesion and aggregation are enhanced. These findings provide further insights into kidney stone formation.

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Section: Cell Culturementioning

confidence: 99%

Reinjury risk of nano-calcium oxalate monohydrate and calcium oxalate dihydrate crystals on injured renal epithelial cells: aggravation of crystal adhesion and aggregation

Gan¹,

Sun²,

Bhadja³

et al. 2016

IJN

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“…The proteases would degrade the protein phase, thus providing a conduit for their further infiltration into the mineral, which would increase the area of exposed crystal surface and thus facilitate crystal mineral dissolution in the acidic interior. In a previous study we demonstrated qualitatively that Madin-Darby canine kidney (MDCK-II) cells, which exhibit features of proximal/distal tubule cells (50), caused more extensive degradation of COM crystals generated from centrifuged and filtered urine, than those precipitated from the corresponding ultrafiltered (UF) urine (7). The aims of this investigation were 1) to measure the nonuniform strain and crystallite size of COM crystals precipitated from urine containing increasing amounts of the soluble crystal matrix extract (CME) derived from urinary COM crystals and 2) to compare quantitatively their rates of dissolution after attachment to renal epithelial cells.…”

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confidence: 99%

Intracrystalline urinary proteins facilitate degradation and dissolution of calcium oxalate crystals in cultured renal cells

Grover¹,

Thurgood²,

Fleming³

et al. 2008

American Journal of Physiology-Renal Physiology

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134: 5-14, 2001. The aim of this investigation was to determine the effect of increasing concentrations of intracrystalline protein on the rate of CaOx crystal dissolution in Madin-Darby canine kidney (MDCKII) cells. Crystal matrix extract (CME) was isolated from urinary CaOx monohydrate (COM) crystals. Cold and [ 14 C]oxalate-labeled COM crystals were precipitated from ultrafiltered urine containing 0 -5 mg/l CME. Crystal surface area was estimated from scanning electron micrographs, and synchrotron X-ray diffraction was used to determine nonuniform strain and crystallite size. Radiolabeled crystals were added to MDCKII cells and crystal dissolution, expressed as radioactive label released into the medium, was measured. Increasing CME content did not significantly alter crystal surface area. However, nonuniform strain increased and crystallite size decreased in a dose-response manner, both reaching saturation at a CME concentration of 3 mg/ and demonstrating unequivocally the inclusion of increasing quantities of proteins in the crystals. This was confirmed by Western blotting. Crystal dissolution also followed saturation kinetics, increasing proportionally with final CME concentration and reaching a plateau at a concentration of ϳ2 mg/l. These findings were complemented by field emission scanning electron microscopy, which showed that crystal degradation also increased relative to CME concentration. Intracrystalline proteins enhance degradation and dissolution of CaOx crystals and thus may constitute a natural defense against urolithiasis. The findings have significant ramifications in biomineral metabolism and pathogenesis of renal stones. nephrocalcinosis; urolithiasis THE PATHOGENESIS OF RENAL calculi requires the sequential combination of two processes, namely, the nucleation of crystals and their retention within the kidney. While crystal nucleation requires supersaturation of urine with calcium oxalate (CaOx), renal crystal trapping has been explained by either the "free particle" or "fixed particle" theory. Although both these theories appear equally plausible (26), current consensus favors a fixed particle mechanism. This view is supported by the results of studies performed in the early 1990s, which demonstrated for the first time that CaOx crystals irreversibly adhere to and are phagocytosed by cultured renal epithelial cells (35,39). These findings introduced a new paradigm to urolithiasis research because they validated the credibility of using this experimental approach to examine and manipulate factors affecting the regulation of crystal retention, which had not previously been possible. Consequently, there followed a series of reports investigating factors affecting interactions between CaOx monohydrate (COM) crystals and renal cells (reviewed in Refs. 30 and 38). Those studies showed that COM crystals, which are the predominant form of CaOx occurring in human kidney stones (41), are highly membranolytic (55), and also that their adherence to renal epithelial cells is very rapid, concentration ...

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“…Consequently, crystals move from the tubular lumen to the interstitum of the kidney [9][10][11][18][19][20]. In this case, it was observed ultrastructurally that some crystal ghosts are extending from the tubular epithelium to the interstitium through the basement membrane, which suggests that similar transport of calcium oxalate crystals from the luminal surface to the peritubular interstitium might also occur in the present case.…”

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confidence: 54%

A Case of Renal Oxalosis in a 3-Month-Old Cat Raised under Controlled Conditions

Suzuki

Uetsuka

Doi

et al. 2012

The Journal of Veterinary Medical Science

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ABSTRACT. The kidneys of a 3-month-old female cat were examined. The cat which had been raised under controlled conditions with no history of any poisoning showed progressive weight loss with increases in blood BUN and creatinine concentrations. At necropsy, both kidneys were firm in consistency with formation of focal scars. Histopathologically, widespread deposition of crystals was observed in the renal tubules (in both dilated lumina and degenerative epithelia) accompanying mild interstitial fibrosis with lymphocyte infiltration. The crystals were colorless or basophilic on the hematoxilin and eosin-stained section and could be visualized with polarized light as doubly fractile crystals. The crystals were identified as calcium oxalate crystals by histochemical examinations using von Kossa stain and alizarin red S stain under different conditions and by ultrastructural examination. Judging from the above-mentioned findings, the present renal lesion detected in an infant cat was diagnosed as renal oxalosis which was suspected to be hereditary in nature. Oxalosis is characterized by widespread deposition of calcium oxalate crystals in the kidneys, bones, arterial media and myocardium, following increased concentrations of oxalate in body fluids, including the urine (hyperoxaluria) [4-8, 14, 16]. Deposition of calcium oxalate crystals most frequently occurs in the kidneys, resulting in renal failure and/or urolithiasis in severe cases. This renal disorder is called renal oxalosis. This paper describes the results of histopathological, histochemical, and ultrastructural examinations on the kidneys of an infant cat with renal oxalosis.A female mixed-breed cat which had been raised in a laboratory under controlled conditions with no history of any poisoning showed progressive weight loss with increases in BUN (from 140.1 to 388.5 mg/dl in 1 week -reference range 10-30 mg/dl) and creatinine (from 3.56 to 7.94 mg/dl in 1 week -reference range 0.8-1.4 mg/dl) concentrations, indicators of renal tubule disorder. At 3 months of age, the cat was euthanized and subjected to postmortem examination in the laboratory. At necropsy, both kidneys were firm in consistency with formation of focal scars. In the other organs, there were no gross abnormalities observed.The kidneys were sent to the authors' laboratory for histopathological, histochemical and ultrastructural examinations. Renal tissues were fixed in 4% phosphate-buffered paraformaldehyde (PFA) solution, embedded in paraffin, sectioned at 4 μm, and stained with hematoxylin and eosin (HE). Some sections were also subjected to von Kossa stain, alizarin red S stain with a modification of the previously published procedure [6,17], periodic acid-Schiff (PAS) reaction, periodic acid-methenamine-silver (PAM) stain, masson trichrome stain or phosphotungstic acid hematoxylin (PTAH) stain.For ultrastructural examination, small pieces of the PFAfixed tissues were post-fixed in 1% osmium tetroxide and embedded in epoxy resin. Ultrathin sections were doublestained with uranyl acetate...

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Internalization of calcium oxalate crystals by renal tubular cells: A nephron segment–specific process?

Cited by 60 publications

References 29 publications

Reinjury risk of nano-calcium oxalate monohydrate and calcium oxalate dihydrate crystals on injured renal epithelial cells: aggravation of crystal adhesion and aggregation

Reinjury risk of nano-calcium oxalate monohydrate and calcium oxalate dihydrate crystals on injured renal epithelial cells: aggravation of crystal adhesion and aggregation

Intracrystalline urinary proteins facilitate degradation and dissolution of calcium oxalate crystals in cultured renal cells

A Case of Renal Oxalosis in a 3-Month-Old Cat Raised under Controlled Conditions

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