Plasma phospholipid arachidonic acid content and calcium metabolism in idiopathic calcium nephrolithiasis

Background. Reports of an increase in plasma and erythrocyte phospholipid a rachidonic acid content and in urinary prostaglandin E-2 (PGE(2)) excretion in patients with idiopathic calcium nephrolithiasis suggested their crucia l role in the pathogenesis of hypercalciuria, a well-known risk factor for lithogenesis. Methods. To confirm this hypothesis, 15 healthy subjects and 20 nephrolithi asis patients were evaluated for plasma phospholipid polyunsaturated fatty acid content and PGE(2) concentration, serum parathyroid hormone, 25 hydrox yvitamin D-3, 1,25-dihydroxyvitamin D-3, and bone-specific alkaline phospha tase levels, as well as urinary excretion of calcium, biochemical markers o f bone resorption (hydroxyproline and crossLaps), and intestinal calcium ab sorption. Furthermore, the effect of a 30-day fish-oil diet supplementation on the previously mentioned parameters was investigated in the patients. Results. At baseline, patients compared with controls showed higher levels of plasma phospholipid arachidonic acid content (P = 0.002). PGE(2) (P = 0. 0004), serum 25-vitamin D-3 (P = 0.001), and 1,25-vitamin D-3 (P = 0.001), urinary excretion of calcium (P = 0.001), hydroxyproline (P = 0.007), and c rossLaps (P = 0.019), as well as intestinal calcium absorption (P = 0.03 at 60 min). Fish oil supplementation induced a reduction in the plasma phosph olipid arachidonic acid level (P < 0.0001), and except for serum concentrat ions of 25-vitamin D-3, normalized baseline blood and urinary parameters, i ncluding intestinal calcium absorption. A close correlation between plasma PGE, and serum 1,25-vitamin D-3 (P = 0.004) and between phospholipid arachi donic acid and intestinal calcium absorption (P = 0.0002) and calciuria (P = 0.007) was observed, as well as between urine excretion of crossLaps and hydroxyproline (P < 0.0001), crossLaps and calcium (P < 0.0001), and hydrox yproline and calcium (P < 0.0001). Conclusions. These findings indicate that the phospholipid arachidonic acid content anomaly could represent the primary event responsible for the mosa ic of metabolic and clinical alterations that are distinctive features of r enal stone formers, and suggest that a common pathogenetic mechanism might account for the several forms of hypercalciuria detected in idiopathic calc ium nephrolithiasis.