Calcium oxalate crystals were grown in the presence of each of the four isoforms of nephrocalcin (NC), a urinary protein proposed to inhibit kidney stone growth. Crystal size, morphology, and surface topography were assessed using optical microscopy, Coulter counter measurements, scanning electron microscopy (SEM), and atomic force microscopy (AFM). All crystals grown in the presence of NC isoforms were calcium oxalate monohydrates (COMs). Crystals formed in the presence of NC-A were smaller than control crystals, which were grown without NC, according to optical and SEM results, suggesting that NC-A restricts crystal growth. In contrast, samples grown with NC-C and NC-D exhibit more large crystals and several crystal aggregates, suggesting that NC-C and -D promote crystal growth and aggregation. Crystals grown with NC-B are not significantly larger or smaller than controls. AFM images of the crystals reveal significantly different surface textures on the control crystals relative to those grown with NC isoforms, indicating that NC acts by coating nascent calcium oxalate crystals. These are the first reported AFM images that show topography of NC-coated crystals. These findings suggest that NC isoforms have distinct interactions with different COM crystal faces, which may be responsible for their different effects on crystal growth and morphology. (C) 2003 Elsevier Science B.V. All rights reserved.