Protein diet and hypercalciuria

In an interesting study in a recent issue of Kidney International, Amanzadeh et al1 reported that a high animal protein diet in rats decreased urinary pH and citrate excretion, and increased urinary calcium and phosphate excretion and bone resorption. The authors concluded that both the kidney and bone contributed to the pathogenesis of hypercalciuria during animal protein excess. In light of our recent studies, we would like to propose another mechanism to explain the origin of hypercalciuria by animal protein ingestion. The increased risk for stone formation by high protein intake could be caused by its effects on membrane phospholipid fatty acid composition, in particular, phospholipid arachidonic acid (AA) level, which plays a crucial role in the pathogenesis of hypercalciuria2,3,4. In fact, a modification in phospholipid AA levels by dietary protein manipulation of delta-6-desaturase, the rate-limiting step of the biosynthetic pathway of highly unsaturated fatty acids, determines in animals and humans a cascade of metabolic effects on intestinal, renal, and bone calcium transport and metabolism, leading to hypercalciuria. It has been demonstrated that AA can influence urinary calcium excretion directly or indirectly through the PGE2/1,25 (OH)2 vitamin D pathway or bone cytokine synthesis2,3,4. A model constructed using the path analysis technique suggests that bone loss in idiopathic hypercalciuric patients is a consequence of the negative calcium balance related to AA-associated high bone turnover and PGE2-induced hypercalciuria, in spite of increased intestinal calcium absorption (unpublished data).