Oxalate-induced changes in renal epithelial cell function: Role in stone disease

Many studies on the etiology of stone disease have focused on the propertie s of urine that affect crystal nucleation and growth. More recent studies h ave focused on the properties of the renal epithelium and the role of injur y in crystal retention. The latter studies have shown that oxalate exposure per se can damage renal epithelial cells and enhance crystal binding. This overview summarizes findings of specific biochemical and genetic alteratio ns observed in renal epithelial cells after exposure to oxalate, In LLC-PK1 and MDCK cells, oxalate exposure produces marked effects on membranes, cau sing a redistribution of phosphatidylserine and activation of two lipid sig naling cascades, one involving phospholipase A(2) (PLA(2)) and one involvin g ceramide, Longer exposure to oxalate leads to membrane damage and cell de ath, Adaptive responses are also observed, including proliferation (for rep lacement of damaged cells) and induction of various genes (for cellular rep lacement and repair). Many or all of these responses are blocked by antioxi dants, and many can be mimicked by PLA(2) agonists/products. This finding s uggests links between oxalate-induced increases in oxidant stress, lipid si gnaling pathways, and subsequent molecular responses that may eventuate in renal cell damage or death. Whether such changes play a role in stone disea se in vivo, and whether strategies to inhibit these changes would be benefi cial therapeutically, is unknown.