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

Abstract

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.

Nephroprotective and Diuretic Effect of Nigella Sativa L Seeds Oil on Lithiasic Wistar Rats

“…This model was approved to trigger urolithiasis kind of CaOx kind by calcium oxalate crystallisation and the high oxalate rate in the nephron damage the epithelial cells. However, crystals aggregation can begin after heterogeneous crystal nucleation (Scheid et al 2004;Thamilselvan et al 2003). Therefore, we investigated the effect of Nigella sativa L. seeds oil against EG and AC generates CaOx urinary calculi formation in Wistar male rats.…”

Lithotriptic Effect of Combination of Matsyakshi (Alternanthera Sessilis Linn. R.BR.,) and Tender Coconut Water in Albino Rats

“…High oxalate levels in nephrons damage epithelial cells, and also result in heterogeneous crystal nucleation and aggregation. 23 . These calcium oxalate crystals decrease the Glomerular Filtration Rate due to the obstruction to the urine out flow.…”

Protective effect of magnesium lactate gluconate and Garcinia cambogia fruit extract in experimentally induced renal calculi in rats

“…Scientific studies have shown that EG is readily absorbed from the intestine and metabolized in the liver to oxalate causing hyperoxaluria [33,34]. Furthermore, increased availability of oxalate substrate in EG-administered animals activates oxalate-synthesizing enzymes (glycolic acid oxidase and lactate dehydrogenase), catalyzing oxidation, and reduction of glyoxylate and glycolate into oxalate leading to hyperoxaluria [35,36].…”

“…Furthermore, increased availability of oxalate substrate in EG-administered animals activates oxalate-synthesizing enzymes (glycolic acid oxidase and lactate dehydrogenase), catalyzing oxidation, and reduction of glyoxylate and glycolate into oxalate leading to hyperoxaluria [35,36]. Excess oxalate present in urine forms water insoluble CaOx precipitates (by nucleation and aggregation) and subsequent retention, causing damage to epithelial linings of renal tubules [33,34].…”