Nephrolithiasis: a consequence of renal epithelial cell exposure to oxalate and calcium oxalate crystals.
OBJECTIVE
Formation of calcium oxalate (CaOx) kidney stones was investigated using three approaches.


METHODS
Pathogenesis of crystalluria and crystal deposition in the kidneys was examined in vivo by inducing hyperoxaluria in rats. Cultures of LLC-PK1 and MDCK cells were exposed to oxalate (Ox) and CaOx crystals to examine the effect on cells in various sections of the renal tubules. The nucleation potential of various substrates was examined by incubating them in metastable solutions of CaOx.


RESULTS
Calcium oxalate crystals and nonphysiologic levels of Ox were injurious to renal epithelial cells. To combat these nephrotoxins, renal epithelial cells produce a variety of macromolecules such as bikunin and osteopontin, which are modulators of crystallization and may also be involved in crystal attachment to the cells. Sustained hyperoxaluria in association with CaOx crystals induced apoptosis as well as necrosis. Cellular degradation products induced heterogeneous nucleation of crystals at lower and physiologic levels of oxalate. They also promoted aggregation.


CONCLUSIONS
Crystals begin to form in earlier segments of the nephron with a chance to grow and be retained in the collecting ducts after aggregation with other large crystals. Crystal deposits in the collecting ducts near the papillary surface, when exposed to the renal pelvic urine, become nidi for the development of kidney stones.
Khan
S R
SR
Department of Pathology, College of Medicine, University of Florida, Gainesville, Florida 32610-0275, USA. Khan@pathology.ufl.edu
Thamilselvan
S
S
D000818:Animals; D002129:Calcium Oxalate / Q000378:metabolism*; D002449:Cell Aggregation; D002460:Cell Line; D003460:Crystallization; D004285:Dogs; D019855:Ethylene Glycol / Q000494:pharmacology; D006801:Humans; D006959:Hyperoxaluria / Q000209:etiology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007669:Kidney Calculi / Q000209:etiology* / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D015227:Lipid Peroxidation; D008562:Membrane Glycoproteins / Q000378:metabolism; D009336:Necrosis; D053495:Osteopontin; D010070:Oxalates / Q000378:metabolism*; D051381:Rats; D012795:Sialoglycoproteins / Q000378:metabolism; D013997:Time Factors; D014360:Trypsin Inhibitor, Kunitz Soybean
D008562:Membrane Glycoproteins; D010070:Oxalates; C109148:SPINT2 protein, human; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin; D002129:Calcium Oxalate; D014360:Trypsin Inhibitor, Kunitz Soybean; D019855:Ethylene Glycol