Effects of luminal oxalate or calcium oxalate on renal tubular cells in culture.
Oxalate or calcium oxalate crystal-induced tissue damage could be conducive to renal stone disease. We studied the response of renal proximal (LLC-PK1 and MDCK-II) and collecting (RCCD1 and MDCK-I) tubule cell lines to oxalate ions as well as to calcium oxalate monohydrate (COM) crystals. Cells grown on tissue culture plastic or permeable growth substrates were exposed to high (1 mM) and extremely high (5 and 10 mM) oxalate concentrations, or to a relatively large quantity of crystals (146 microg), after which cell morphology, prostaglandin E(2) (PGE(2)) secretion, [(3)H]thymidine incorporation, total cell numbers and various forms of cell death were studied. Morphological alterations, increased PGE(2) secretion, elevated levels of DNA synthesis and necrotic cell death were induced by extremely high, but not by high oxalate. Crystals were rapidly internalized by proximal tubular cells, which stimulated PGE(2) secretion and DNA synthesis and the release of crystal-containing necrotic cells from the monolayer. Crystals did not bind to, were not taken up by, and did not cause marked responses in collecting tubule cells. These results show that free oxalate is toxic only at supraphysiological concentrations and that calcium oxalate is toxic only to renal tubular cells that usually do not encounter crystals. Based on these results, it is unlikely that oxalate anions or calcium oxalate crystals are responsible for the tissue damage that may precede renal stone formation.
Verkoelen
C F
CF
Department of Urology, Erasmus Medical Center, Rotterdam, The Netherlands. c.verkoelen@erasmusmc.nl
Schepers
M S J
MS
van Ballegooijen
E S
ES
Bangma
C H
CH
D000818:Animals; D000838:Anions; D017209:Apoptosis / Q000187:drug effects; D002129:Calcium Oxalate / Q000494:pharmacology*; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D004285:Dogs; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009336:Necrosis; D019815:Oxalic Acid / Q000494:pharmacology*
D000838:Anions; D002129:Calcium Oxalate; D019815:Oxalic Acid; D015232:Dinoprostone