The changes in urinary crystal properties in patients with calcium oxalate (CaOx) calculi after oral administration of potassium citrate (K3cit) were investigated via atomic force microscopy (AFM), scanning electron microscopy (SEM), X-ray powder diffractometry (XRD), and zeta potential analyzer. The AFM and SEM results showed that the surface of urinary crystals became concave, the edges and corners of crystals became blunt, the average size of urinary crystallines decreased significantly, and aggregation of urinary crystals was reduced. These changes were attributed to the significant increase in concentration of excreted citrate to ？mg/L after K3cit intake from ？mg/L before K3cit intake. After the amount of urinary citrate was increased, it complexed with Ca2+ ions on urinary crystals, which dissolved these crystals. Thus, the appearance of concave urinary crystals was a direct evidence of CaOx dissolution by citrate in vivo. The XRD results showed that the quantities and species of urinary crystals decreased after K3cit intake. The mechanism of inhibition of formation of CaOx stones by K3cit was possibly due to the complexation of Ca2+ with citrate, increase in urine pH, concentration of urinary inhibitor glycosaminoglycans (GAGs), and the absolute value of zeta potential after K3cit intake. 1. Introduction Nephrolithiasis, characterized by renal calculi, is a disorder that has recently shown a trend of rising incidence around the world. Renal calculi mainly contain calcium oxalate (CaOx) crystals [1]. However, knowledge about its pathogenesis is limited thus far [2, 3], and the high recurrence rate is still an important clinical issue [4]. Although CaOx is supersaturated in urine, the formation of renal calculi in healthy people is difficult because of all kinds of inhibitors in urine, including citrate, magnesium, osteopontin, and tyrosine hydroxylase [5]. Chemically speaking, CaOx calculi formation is closely related to with the following factors: high concentration of calcium and oxalate in urine, nucleation, growth and aggregation of CaOx crystals, and adhesion of calcium oxalate monohydrate (COM) to renal tubular epithelial cells [6]. CaOx calculi formation is thought to follow two main routes, (slow) formation of subepithelial plaques at papillary tips and (rapid) formation of intratubular plugs [7]. Potassium citrate (K3cit) is one of the main drugs for treatment and prevention of renal calculi. In July 1985, the US Food and Drug Administration approved K3cit as a single drug to treat CaOx calculi with low urinary citrate and uric acid
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