Apatite Induced Renal Epithelial Injury: Insight Into the Pathogenesis of Kidney Stones
- 31 July 2008
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of Urology
- Vol. 180 (1), 379-387
- https://doi.org/10.1016/j.juro.2008.02.041
Abstract
Purpose: Kidney stone formation is associated with the deposition of hydroxyapatite as subepithelial plaques or tubular deposits in the renal papillae. We investigated the effect of renal epithelial exposure to hydroxyapatite crystals in vitro to develop an insight into the pathogenesis of kidney stones. Materials and Methods: NRK52E cells (No. CRL-1571, ATCC®) were exposed to 67 or 133 μg/cm2 hydroxyapatite (No. 21223, Sigma-Aldrich™) or calcium oxalate monohydrate crystals (No. 27609, BDH Industries, Poole, United Kingdom). In some studies cells were also exposed to crystals from the basal side. After 3 or 6 hours of exposure medium was analyzed for lactate dehydrogenase, 8-isoprostane and H2O2. Medium collected after cell exposure on the apical side was also analyzed for the production of monocyte chemoattractant protein-1 and prostaglandin E2. Cells were stained with DAPI to determine apoptotic activity and examined by scanning electron microscopy to observe crystal-cell interaction. Results: Cell exposure to hydroxyapatite resulted in H2O2 and 8-isoprostane production as well as in lactate dehydrogenase release. Apical exposure appeared more provocative and injurious than basal exposure. Exposure to hydroxyapatite for 6 hours resulted in increased apoptotic activity. Apical exposure also resulted in increased monocyte chemoattractant protein-1 and prostaglandin E2 production. Conclusions: Cell exposure to hydroxyapatite crystals induced oxidative stress and lipid peroxidation. It caused up-regulation of the inflammation mediators that may be responsible for the kidney inflammation in patients with stones that is associated with tubular hydroxyapatite deposition. It may also have a role in the eruption of subepithelial Randall's plaques to the papillary surface.Keywords
This publication has 21 references indexed in Scilit:
- Naturally produced crystals obtained from kidney stones are less injurious to renal tubular epithelial cells than synthetic crystalsBJU International, 2007
- Proposed mechanisms in renal tubular crystal retentionKidney International, 2007
- Modeling of hyperoxaluric calcium oxalate nephrolithiasis: Experimental induction of hyperoxaluria by hydroxy-L-prolineKidney International, 2006
- Crystals cause acute necrotic cell death in renal proximal tubule cells, but not in collecting tubule cellsKidney International, 2005
- Biologic effects of calcium-containing crystalsCurrent Opinion in Rheumatology, 2005
- Calcium phosphate–induced renal epithelial injury and stone formation: Involvement of reactive oxygen speciesKidney International, 2003
- Is precipitation of calcium phosphate an important factor for the development of calcium oxalate stones in the urinary tractFrontiers in Bioscience-Landmark, 2003
- Oxalate Selectively Activates p38 Mitogen-activated Protein Kinase and c-Jun N-terminal Kinase Signal Transduction Pathways in Renal Epithelial CellsPublished by Elsevier BV ,2002
- Lipid Peroxidation in Ethylene Glycol Induced Hyperoxaluria and Calcium Oxalate NephrolithiasisJournal of Urology, 1997
- Calcium oxalate nephrolithiasis, a free or fixed particle diseaseKidney International, 1994