Oxalate: From crystal formation to crystal retention

Idiopathic calcium oxalate stone formation is a multifactorial disease. It is therefore unlikely that a single underlying condition will be responsibl e for entire spectrum of the disease; however, it appears that one importan t factor in the pathogenesis is an abnormality in oxalate metabolism. Whate ver the cause, two critical parameters for stone formation are crystal form ation and crystal retention in the renal tubules. Although crystal formatio n and role of oxalate in crystal formation have been evaluated extensively, it is only recently that crystal retention has been addressed. Previous st udies from our laboratories demonstrated that oxalate exposure to renal epi thelial cells in culture resulted in initiation of a program of events incl uding DNA synthesis and cell death. The present studies evaluated effects o f oxalate on cell proliferation and damage to distal tubular (Madin-Darby c anine kidney cells) and proximal (LLC-PK1 cells) cells. Effects of oxalate exposure on calcium oxalate monohydrate (COM) crystal adherence to these ce lls were also evaluated. Results presented herein demonstrate that proximal tubular cells are more sensitive to oxalate than distal tubular cells. Fur thermore, oxalate exposure to proximal tubular cells resulted in reinitiati on of DNA synthesis, whereas no such effect was observed in distal tubular cells. Higher levels of oxalate (> 1mM) resulted in cell loss of both proxi mal and distal tubular cells, as observed by crystal violet staining. Despi te these differences, oxalate exposure to both proximal and distal tubular cells resulted in increased COM crystal adherence. Thus, oxalate exposure m ay promote crystal adherence to renal epithelial cells either secondarily t o cell death and proliferation or by a yet unidentified mechanism. These st udies provide the first direct evidence for the role of oxalate in promotin g COM crystal retention by the urothelium.