Anomalous Phospholipid n-6 Polyunsaturated Fatty Acid Composition in Idiopathic Calcium Nephrolithiasis

Abstract

Anomalies in the erythrocyte transport of onions and cations have been described in idiopathic calcium oxalate nephrolithiasis and seem to play a pathogenetic role in this disease. In consideration of the hypothesis that the complex array of ion flux cell abnormalities is an epiphenomenon of an anomaly in the composition of cell membranes, this study investigated cell-membrane lipid composition. In idiopathic calcium oxalate renal stone formers, in which ion transport abnormalities were present, and in healthy control subjects, plasma and erythrocyte membrane lipid composition, the erythrocyte oxalate exchange, and Na/K/2Cl cotransport activity were evaluated. Furthermore, in stone formers, the effect of a 30-day fish-oil diet supplementation on plasma lipids, erythrocyte oxalate exchange, oxaluria, and calciuria was investigated. The effect of arachidonic acid released by phospholipase A2 on anion-carrier phosphorylation and activity in erythrocytes was evaluated as well. Patients had a lower content of linoleic and higher concentration of arachidonic acids in both plasma and erythrocyte membrane phospholipids, and an increased arachidonic/linoleic acid ratio. The arachidonic acid level correlated with the erythrocyte oxalate exchange and sodium cotransport activity. Fish-oil supplementation lowered calcium and oxalate urine excretion, and normalized the erythrocyte oxalate exchange. Phospholipase A2 increased the erythrocyte anion-carrier protein phosphorylation and the oxalate exchange. This study shows that idiopathic calcium nephrolithiasis in the patient group reported here is characterized by a systemic defect in phospholipid arachidonic acid levels that might provide an answer to the link between genetic background, dietary habits, and renal lithiasis.