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The majority of human urinary stones are primarily composed of calcium salts. Although normal urine is frequently supersaturated with respect to calcium oxalate, most humans do not form stones. Inhibitors are among the multiple factors that may influence the complex process of urinary stone formation. We have isolated an inhibitor of calcium oxalate crystal growth from human urine by monoclonal antibody immunoaffinity chromatography. The N-terminal amino acid sequence and acidic amino acid content of this aspartic acid-rich protein, uropontin, are similar to those of other pontin proteins from bone, plasma, breast milk, and cells. The inhibitory effect of uropontin on calcium oxalate crystal growth in vitro supports the concept that pontins may have a regulatory role. This function would be analogous to that of other members of the aspartic acid-rich protein superfamily, which stereospecifically regulate the mineralization fronts of calcium-containing crystals.

The influence of prior glomerular mesangial uptake of a macromolecule that induces the infiltration of macrophages (M phi) into the mesangium on the uptake of a second macromolecule by the mesangium was studied in inbred Lewis rats. Renal transplantation of kidneys from rats previously injected with polyvinyl alcohol (PVA) was performed to avoid the potential influences of ongoing uptake of PVA and altered host milieu on the glomerular uptake of iron dextran (ID), a macromolecule that localizes primarily in the intrinsic mesangial cells of unmodified rats. In contrast to that in the recipient's native kidney, the uptake of ID was markedly increased in the glomeruli in kidneys previously exposed to PVA. This enhanced uptake was the consequence of the phagocytic activity of mesangial M phi elicited by and containing PVA since the site of increased ID content was shown by ultrastructural studies to be within mesangial M phi. Isogeneic renal transplantation per se did not influence mesangial function since the glomerular uptake of ID in donor and recipient kidneys was the same when donors were normal rats. In addition to the enhanced uptake of ID into lysosomes by mesangial M phi these cells were also much more active in the further processing of ID to ferritin particles within the cytoplasm than were intrinsic mesangial cells. These studies demonstrate that M phi attracted to the mesangium by a stimulus such as PVA may have important effects on the consequences of additional challenges to the mesangium.