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.