Dietary manipulation of Delta-6-desaturase modifies phospholipid arachidonic acid levels and the urinary excretion of calcium and oxalate in the rat:Insight in calcium lithogenesis

An anomalous n-6 polyunsaturated fatty acid composition in plasma and eryth rocyte membrane phospholipids, namely increased levels of arachidonic acid (AA), has been reported in calcium nephrolithiasis and has been proposed to play an important role in its pathogenesis. To confirm this, in rats we mo dified phospholipid AA levels by dietary manipulation of the Delta-6-desatu rase, the rate-limiting enzyme of the fatty acid biosynthetic pathway, and evaluated the effect on cellular and renal functions predisposing to lithog enesis. Increased AA levels led to conditions at risk for nephrolithiasis: higher oxalate flux and lower sodium cotransport in erythrocytes and a rise in urinary prostaglandin E-2, calcium, sodium, and oxalate levels; reduced AA levels reversed these changes. In vitro, in human erythrocytes the inco rporation of exogenous AA into membranes increased band 3 protein phosphory lation directly activating the Ser/Thr protein kinase CK1 and induced a par allel raise in band 3-mediated oxalate transport. These findings demonstrat e the pivotal role of phospholipid AA in modulating erythrocyte and renal t ransport of calcium and oxalate.