Effects of luminal oxalate or calcium oxalate on renal tubular cells in culture

Abstract

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.

Peroxisome proliferator‐activated receptor γ modulates renal crystal retention associated with high oxalate concentration by regulating tubular epithelial cellular transdifferentiation

“…Some papers (Kim, Kwak, Jeong, & Kim, ; Werness, Brown, Smith, & Finlayson, ) have reported that high concentrations of oxalate (1 mM) led to cell apoptosis in MDCK cells; however, Verkoelen, Schepers, van Ballegooijen, and Bangma () reported that cell apoptosis can be induced by extremely high oxalate concentration (5 and 10 mM) but not by high oxalate concentration. Borges et al () and Verkoelen et al () have confirmed this finding.…”

Cu-bearing stainless steel reduces cytotoxicity and crystals adhesion after ureteral epithelial cells exposing to calcium oxalate monohydrate

“…A high concentration of oxalate contributes to COM precipitation. Oxalate and/or COM induce cellular oxidative stress in the kidneys with increasing free radical production, which creates a harmful environment for macromolecules and results in cell damage and even apoptosis or cell death 9–12 . Moreover, different types crystals generate different amounts of ROS, but to be sure, they all show toxicity to cells 13 .…”

Renal prothrombin mRNA is significantly decreased in a hyperoxaluric rat model of nephrolithiasis

“…Both are known to have cytotoxic effects on cultured renal cells 45–48. However, although earlier investigations showed that oxalate is cytotoxic at concentrations as low as 250 µ M (reviewed in 45), more recent studies have reported it to be innocuous up to 5 m M 47–50, which is the highest urinary oxalate concentration to have been documented in the hyperoxaluric rat model of nephrolithiasis 18. Furthermore, one of those studies 48 showed that oxalate cytotoxicity resulted specifically from the formation of COM crystals.…”