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 responsible for entire spectrum of the disease; however, it appears that one important factor in the pathogenesis is an abnormality in oxalate metabolism. Whatever the cause, two critical parameters for stone formation are crystal formation and crystal retention in the renal tubules. Although crystal formination and role of oxalate in crystal formation have been evaluated extensively, it is only recently that crystal retention has been addressed. Previous studies from our laboratories demonstrated that oxalate exposure to renal epithelial cells in culture resulted in initiation of a program of events including DNA synthesis and cell death. The present studies evaluated effects of oxalate on cell proliferation and damage to distal tubular (Madin-Darby canine kidney cells) and proximal (LLC-PK1 cells) cells. Effects of oxalate exposure on calcium oxalate monohydrate (COM) crystal adherence to these cells were also evaluated. Results presented herein demonstrate that proximal tubular cells are more sensitive to oxalate than distal tubular cells. Furthermore, oxalate exposure to proximal tubular cells resulted in reinitiation of DNA synthesis, whereas no such effect was observed in distal tubular cells. Higher levels of oxalate (> 1 mM) resulted in cell loss of both proximal and distal tubular cells, as observed by crystal violet staining. Despite these differences, oxalate exposure to both proximal and distal tubular cells resulted in increased COM crystal adherence. Thus, oxalate exposure may promote crystal adherence to renal epithelial cells either secondarily to cell death and proliferation or by a yet unidentified mechanism. These studies provide the first direct evidence for the role of oxalate in promoting COM crystal retention by the urothelium.
Koul
H K
HK
Urology Research Laboratories, Henry Ford Health Sciences Center, Detroit, Michigan 48202, USA. hkoul1@hfhs.org
Koul
S
S
Fu
S
S
Santosham
V
V
Seikhon
A
A
Menon
M
M
D000818:Animals; D002129:Calcium Oxalate / Q000737:chemistry*; D002478:Cells, Cultured; D003460:Crystallization; D004247:DNA / Q000096:biosynthesis; D004285:Dogs; D007668:Kidney / Q000378:metabolism*; D013552:Swine; D014545:Urinary Calculi / Q000209:etiology*
D002129:Calcium Oxalate; D004247:DNA