Apatite Induced Renal Epithelial Injury: Insight Into the Pathogenesis of Kidney Stones

Escobar, Carmen; Byer, Karen J.; Khaskheli, Hassan; Khan, Saeed R.

doi:10.1016/j.juro.2008.02.041

Cited by 41 publications

(23 citation statements)

References 20 publications

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“…Exposure of the renal epithelial cells to oxalate and/or CaOx/CaP crystals leads to the production of reactive oxygen species, [108–116] with the activation of NADPH oxidase, [117–122] through the involvement of renin angiotensin aldosterone pathway. [118,123] Renal epithelial cells under oxidative stress may become osteogenic [124] as happens to vascular smooth muscle cells during vascular calcification.…”

Section: Regulation Of Randall’s Plaque Formationmentioning

confidence: 99%

Unified theory on the pathogenesis of Randall’s plaques and plugs

2014

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Kidney stones develop attached to sub-epithelial plaques of calcium phosphate (CaP) crystals (termed Randall’s plaque) and/or form as a result of occlusion of the openings of the Ducts of Bellini by stone forming crystals (Randall’s plugs). These plaques and plugs eventually extrude into the urinary space, acting as a nidus for crystal overgrowth and stone formation. To better understand these regulatory mechanisms and the pathophysiology of idiopathic calcium stone disease, this review provides in-depth descriptions of the morphology and potential origins of these plaques and plugs, summarizes existing animal models of renal papillary interstitial deposits, and describes factors that are believed to regulate plaque formation and calcium overgrowth. Based on evidence provided within this review and from the vascular calcification literature, we propose a “unified” theory of plaque formation – one similar to pathological biomineralization observed elsewhere in the body. Abnormal urinary conditions (hypercalciuria, hyperoxaluria, hypocitraturia), renal stress or trauma, and perhaps even the normal aging process leads to transformation of renal epithelial cells into an osteblastic phenotype. With this de-differentiation comes an increased production of bone specific proteins (i.e. osteopontin), a reduction in crystallization inhibitors (such as fetuin and matrix-gla-protein), and creation of matrix vesicles, which support nucleation of CaP crystals. These small deposits promote aggregation and calcification of surrounding collagen. Mineralization continues by calcification of membranous cellular degradation products and other fibers until the plaque reaches the papillary epithelium. Through the activity of matrix metalloproteinases or perhaps by brute physical force produced by the large subepithelial crystalline mass, the surface is breached and further stone growth occurs by organic matrix-associated nucleation of CaOx or by the transformation of the outer layer of CaP crystals into CaOx crystals. Should this theory hold true, developing an understanding of the cellular mechanisms involved in progression of a small, basic interstitial plaque to that of an expanding, penetrating plaque could assist in the development of new therapies for stone prevention.

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Section: Regulation Of Randall’s Plaque Formationmentioning

confidence: 99%

Unified theory on the pathogenesis of Randall’s plaques and plugs

2014

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“…28 Therefore, aside from the aforementioned selection of different blank values, this inconsistency can also be attributed to the strong endocytosic ability of Vero cells to submicron COD (150 ± 50 nm) that can easily induce the inflammation response. As the adhesion time prolonged, the submicron COD gradually gathered into micron-level crystals (Figures 2 and 3), thereby reducing their cell damage effects.…”

Section: Adhesion Between Vero Cells In the Injury Group And Cod Micrmentioning

confidence: 99%

Interaction between submicron COD crystals and renal epithelial cells

Peng¹,

Ouyang²,

Yao³

et al. 2012

IJN

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Objectives: This study aims to investigate the adhesion characteristics between submicron calcium oxalate dihydrate (COD) with a size of 150 ± 50 nm and African green monkey kidney epithelial cells (Vero cells) before and after damage, and to discuss the mechanism of kidney stone formation. Methods: Vero cells were oxidatively injured by hydrogen peroxide to establish a model of injured cells. Scanning electron microscopy was used to observe Vero-COD adhesion. Inductively coupled plasma emission spectrometry was used to quantitatively measure the amount of adhered COD microcrystals. Nanoparticle size analyzer and laser scanning confocal microscopy were performed to measure the change in the zeta potential on the Vero cell surface and the change in osteopontin expression during the adhesion process, respectively. The level of cell injury was evaluated by measuring the changes in malonaldehyde content, and cell viability during the adhesion process. Results: The adhesion capacity of Vero cells in the injury group to COD microcrystals was obviously stronger than that of Vero cells in the control group. After adhesion to COD, cell viability dropped, both malonaldehyde content and cell surface zeta potential increased, and the fluorescence intensity of osteopontin decreased because the osteopontin molecules were successfully covered by COD. Submicron COD further damaged the cells during the adhesion process, especially for Vero cells in the control group, leading to an elevated amount of attached microcrystals. Conclusion: Submicron COD can further damage injured Vero cells during the adhesion process. The amount of attached microcrystals is proportional to the degree of cell damage. The increased amount of microcrystals that adhered to the injured epithelial cells plays an important role in the formation of early-stage kidney stones.

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“…aggregation, retention and stone development (Escobar et al, 2008;Byer and Khan, 2003;Vanachayangkul et al, 2011). The antiurolithic effect of O. vulgaris was evaluated on the ethylene glycol-induced model for urolithiasis (Divakar et al, 2010;Tsai et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Antiurolithic and antihypertensive activities of Origanum vulgaris on urolithic rats

ElSawy¹,

Shaheen²,

Filimban³

et al. 2015

J. Med. Plants Res.

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Origanum vulgaris (Oregano) has been used in the fluky medicinal for treating various diseases including urolithiasis and hypertension. This study was designed to investigate the possible antioxidant and antiurolithic activities of different standardized extracts of Oregano ethanol extract n-hexane, ethyl acetate, and aqueous fraction on rats. The dried hydroalcoholic extract of 70% ethyl alcohol Oregano was suspended in water and successively extracted with n-hexane and ethyl acetate. Each active extract was screened of phytochemical and standardized spectrophotometricaly by estimation of total phenol and total flavonoid content. Antiurolithic and antioxidant activities were studied on live rat model by oral doses of ethylene glycol and NH 4 Cl. The active extracts of Oregano (20 mg/kg) were given to different groups and one group without extracts was used as control. At the end of the experimental period, blood samples were obtained from studying biochemical parameters and a kidney specimen for histopathology using scanning electron microscope. Ethanol extract, n-hexane and aqueous fractions prevented as well as opposed toxic changes, including loss of body weight gain and appetite, raised serum urea, uric acid and creatinine levels, and crystal deposition in the kidneys. These potential urolithitic effects of ethylene glycol should be taken into considerations with close monitoring of kidney function tests at frequent intervals. The oregano antioxidant effect might be more effective in the amelioration of ethylene glycol induced kidney injury and urolithiasis.

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Apatite Induced Renal Epithelial Injury: Insight Into the Pathogenesis of Kidney Stones

Cited by 41 publications

References 20 publications

Unified theory on the pathogenesis of Randall’s plaques and plugs

Unified theory on the pathogenesis of Randall’s plaques and plugs

Interaction between submicron COD crystals and renal epithelial cells

Antiurolithic and antihypertensive activities of Origanum vulgaris on urolithic rats

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