Calcium phosphate–induced renal epithelial injury and stone formation: Involvement of reactive oxygen species

Aihara, Kinue; Byer, Karen J.; Khan, Saeed R.

doi:10.1046/j.1523-1755.2003.00226.x

Cited by 106 publications

(84 citation statements)

References 42 publications

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“…We have shown earlier that renal epithelial cells react to the presence of brushite and CaOx crystals in time and concentration dependent manner (3,4). Longer exposure to high concentrations of brushite or CaOx crystals is injurious to the renal epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2008

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Purpose-Kidney stone formation is associated with the deposition of hydroxyapatite (HA) either as sub-epithelial plaques or tubular deposits in the renal papillae. We investigated the effect of renal epithelial exposure to HA crystals in vitro to develop an insight into the pathogenesis of kidney stones.Materials and methods-NRK52E cells were exposed to 67 μg/cm 2 or 133 μg/cm 2 of HA or calcium oxalate monohydrate crystals. In some studies cells were also exposed to crystals from the basal side. After exposure of 3 or 6 hours media were analyzed for, lactate dehydrogenase (LDH), 8-isoprostane (8-IP) and hydrogen peroxide (H 2 O 2 ). Media collected after cells' exposure on the apical side was also analyzed for the production of monocyte chemoattractant-1 (MCP-1) and prostaglandin E2 (PGE2). Cells were stained with DAPI to determine apoptotic activity and examined by SEM to observe crystal-cell interaction.Results-Cell exposure to HA resulted in the production of H 2 O 2 and 8-IP as well as release of LDH. Apical exposure appeared more provocative and injurious than the basal exposure. An exposure to HA for 6 hours, resulted in increased apoptotic activity. Apical exposure also resulted in increased production of MCP-1 and PGE2.Conclusion-Cell exposure to HA crystals induces oxidative stress, lipid peroxidation, and caused upregulation of mediators of inflammation that may be responsible for the inflammation in kidneys of stone patients associated with tubular deposition of HA. They may also play a role in eruption of subepithelial Randall's plaques to the papillary surface.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2008

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“…The urinary calcium excretion increases initially because of the accompanying sodium load that suppresses calcium reabsorption in the proximal tubule. The high concentration of phosphate and calcium in the urine results in precipitation of calcium-phosphate crystals that flow downstream to the distal tubules and collecting ducts and bind to the epithelial cells, where these undergo internalization, triggering an inflammatory reaction and cellular damage [11].…”

Section: Discussionmentioning

confidence: 99%

The perils of protocols: acute phosphate nephropathy after intravenous phosphate replacement

Parmar

2015

Diagnosis

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Protocols are commonly used in the hospitals around the world and enable health care organizations to put evidence into practice and provide a framework for the management of the individual patient. Such standardization of practice is felt to reduce variations in practice and improve quality of care. However, the protocols have advantages and disadvantages. I present a case where activation of the protocols for "Electrolyte, phosphate and magnesium replacement" at the time of admission to the hospital, resulted in harm to the patient because of inappropriate timing of the test(s) with a resulting action to correct the expected laboratory abnormality. Timing of tests and administration of various medications including antibiotics in hospitalized dialysis patients is important, and both the physicians and the nursing staff require vigilance when requesting/performing tests and ordering/ administering medications to dialysis patients.

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“…Excessive ROS can cause inflammation, oxidative stress, and apoptosis. 26,27 As shown in Figure 4, nano-HAp caused MOVASs to produce a large amount of ROS, indicating that nano-HAp induced cell damage. Both Na 3 Cit and Et 2 Cit significantly inhibited ROS production induced by nano-HAp, and strong inhibitory effects were observed at high concentrations ( Figure 4B).…”

Section: Effect Of Nano-hap On Rosmentioning

confidence: 99%

Diethyl citrate and sodium citrate reduce the cytotoxic effects of nanosized hydroxyapatite crystals on mouse vascular smooth muscle cells

Zhang¹,

Sun²,

Ouyang³

et al. 2017

IJN

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Objective This study aimed to investigate the damage mechanism of nanosized hydroxyapatite (nano-HAp) on mouse aortic smooth muscle cells (MOVASs) and the injury-inhibiting effects of diethyl citrate (Et 2 Cit) and sodium citrate (Na 3 Cit) to develop new drugs that can simultaneously induce anticoagulation and inhibit vascular calcification. Methods The change in cell viability was evaluated using a cell proliferation assay kit, and the amount of lactate dehydrogenase (LDH) released was measured using an LDH kit. Intracellular reactive oxygen species (ROS) and mitochondrial damage were detected by DCFH-DA staining and JC-1 staining. Cell apoptosis and necrosis were detected by Annexin V staining. Intracellular calcium concentration and lysosomal integrity were measured using Fluo-4/AM and acridine orange, respectively. Results Nano-HAp decreased cell viability and damaged the cell membrane, resulting in the release of a large amount of LDH. Nano-HAp entered the cells and damaged the mitochondria, and then induced cell apoptosis by producing a large amount of ROS. In addition, nano-HAp increased the intracellular Ca 2+ concentration, leading to lysosomal rupture and cell necrosis. On addition of the anticoagulant Et 2 Cit or Na 3 Cit, cell viability and mitochondrial membrane potential increased, whereas the amount of LDH released, ROS, and apoptosis rate decreased. Et 2 Cit and Na 3 Cit could also chelate with Ca + to inhibit the intracellular Ca 2+ elevations induced by nano-HAp, prevent lysosomal rupture, and reduce cell necrosis. High concentrations of Et 2 Cit and Na 3 Cit exhibited strong inhibitory effects. The inhibitory capacity of Na 3 Cit was stronger than that of Et 2 Cit at similar concentrations. Conclusion Both Et 2 Cit and Na 3 Cit significantly reduced the cytotoxicity of nano-HAp on MOVASs and inhibited the apoptosis and necrosis induced by nano-HAp crystals. The chelating function of citrate resulted in both anticoagulation and binding to HAp. Et 2 Cit and Na 3 Cit may play a role as anticoagulants in reducing injury to the vascular wall caused by nano-HAp.

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Calcium phosphate–induced renal epithelial injury and stone formation: Involvement of reactive oxygen species

Cited by 106 publications

References 42 publications

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

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

The perils of protocols: acute phosphate nephropathy after intravenous phosphate replacement

Diethyl citrate and sodium citrate reduce the cytotoxic effects of nanosized hydroxyapatite crystals on mouse vascular smooth muscle cells

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