Strong inhibition of crystal-cell attachment by pediatric urinary macromolecules: a close relationship with high...

To investigate other reasons for the low incidence of pediatric urolithiasis, we evaluated the difference in the crystal-cell adhesion inhibitory activity of urinary macromolecules (UMMs) between children and adults. We also evaluated whether citrates influence the above inhibitory activity, because citrates are important in pediatric urine.

Urine samples were collected from children and healthy male adults during a 24-hour period, and urinary components with a molecular weight of 3 kDa or greater were extracted as UMMs to compare their inhibitory activity during the adhesion of calcium oxalate monohydrate crystals to cultured Madin-Darby canine kidney cells between children and adults. Subsequently, various concentrations of citrates were added to adult UMMs to evaluate the changes in the crystal-cell adhesion inhibitory activity of UMMs.

Pediatric UMMs more strongly inhibited the adhesion of calcium oxalate monohydrate crystals to cultured Madin-Darby canine kidney cells at a concentration of 0.1 mg/mL compared with adult UMMs. In addition, pediatric UMMs contained higher proportions of fibronectin and glycosaminoglycans, both of which exhibit crystal-cell adhesion inhibitory activity. When citrates were added to adult UMMs, the crystal-cell adhesion inhibitory activity of UMMs was increased in a dose-dependent manner. However, citrates alone did not result in any differences in the inhibitory activity at any of the three different concentrations.

We speculate that the incidence of pediatric urolithiasis is low because pediatric UMMs more potently inhibit the adhesion of calcium oxalate crystals to renal tubular cells or because the higher proportion of citrates in pediatric urine enhances the crystal-cell adhesion inhibitory activity of UMMs in a dose-dependent manner.