How elevated oxalate can promote kidney stone disease: changes at the surface and in the cytosol of renal cells that promote crystal adherence and growth.
The present review assesses the mechanisms by which oxalate-induced alterations in renal cell function may promote stone disease focusing on 1) changes in membrane surface properties that promote the attachment of nascent crystals and 2) changes in the expression/secretion of urinary macromolecules that alter the kinetics of crystal nucleation, agglomeration and growth. The general role of renal cellular injury in promoting these responses and the specific role of urinary oxalate in producing injury is emphasized, and the signaling pathways that lead to the observed changes in cell surface properties and in the viability and growth of renal cells are discussed. Particular attention is paid to evidence linking oxalate-induced activation of cytosolic phospholipase A2 to changes in gene expression and to the activation of a second signaling pathway involving ceramide. The effects of the lipid signals, arachidonic acid, lysophosphatidylcholine and ceramide, on mitochondrial function are considered in some detail since many of the actions of oxalate appear to be secondary to increased production of reactive oxygen molecules within these organelles. Data from these studies and from a variety of other studies in vitro and in vivo were used to construct a model that illustrates possible mechanisms by which an increase in urinary oxalate levels leads to an increase in kidney stone formation. Further studies will be required to assess the validity of various aspects of this proposed model and to determine effective strategies for countering these responses in stone-forming individuals.
Scheid
Cheryl R
CR
University of Massachusetts Medical School, Department of Physiology, 55 Lake Avenue North, Worcester, MA 01655, USA. Cheryl.Scheid@umassmed.edu
Cao
Lu-Cheng
LC
Honeyman
Thomas
T
Jonassen
Julie A
JA
D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D003460:Crystallization; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology; D007669:Kidney Calculi / Q000378:metabolism* / Q000503:physiopathology; D010070:Oxalates / Q000494:pharmacology*
D010070:Oxalates