Correction of erythrocyte abnormalities in idiopathic calcium-oxalate nephrolithiasis and reduction of urinary oxalate by oral glycosaminoglycans.

Abstract

Calcium-oxalate nephrolithiasis is associated with a defect in erythrocyte oxalate self-exchange and an abnormal rate of erythrocyte membrane protein phosphorylation. There is evidence that glycosaminoglycans (GAGs) have a regulatory effect on both of these processes. This study tested the hypothesis that modifications of erythrocyte oxalate self-exchange induced by oral GAGs are paralleled by similar changes in overall oxalate metabolism. 40 patients with idiopathic calcium-oxalate nephrolithiasis were treated for 15 days with 60 mg/day of a mixture of GAGs. By day 15 of treatment there were significant reductions from baseline in erythrocyte oxalate self-exchange (mean [SD] 1.67 [1.18] vs 2.59 [1.63] x 10(2) per min; p less than 0.005) and erythrocyte membrane protein phosphorylation (55.8 [7.3] vs 72.9 [6.8] x 10(-3) cpm/mg protein; p less than 0.005), but also in urinary oxalate excretion (0.24 [0.09] vs 0.31 [0.15] mmol/24 h; p less than 0.005). This finding suggests similar changes in both erythrocytes and other cells more important in oxalate handling. The changes had reversed by 15 days after withdrawal of treatment. Acute intravenous administration of GAGs (60 mg) induced a fall in carbon-14-labelled oxalate renal clearance (143 [13] vs 169 [28] ml/min; p less than 0.005), which strongly suggests the participation of the kidney. However, reduced oxalate absorption from the intestine, and even decreased synthesis of oxalate, cannot be ruled out.