Factors affecting cystine solubility were sought in an effort to derive a reliable method for estimating urinary saturation with respect to cystine. In synthetic solutions, cystine solubility was measured from the maximum ambient cystine concentration reached after incubation with an excess of solid cystine. It rose progressively as the ionic strength increased from addition of mineral electrolytes. The increment in cystine solubility between ionic strength of 0.005 and 0.3 ranged from 13 mg./l. for potassium chloride to 70 mg./l. for calcium chloride. Urinary macromolecules (>5,000 daltons, obtained by ultrafiltration), at concentrations normally expected to be found in urine, increased cystine solubility by as much as 45 mg./l. Because of these actions of electrolytes and macromolecules, cystine solubility in urine (from control subjects and patients with cystinuria) exceeded solubility in synthetic solution containing 5 mM sodium cacodylate by 68 to 89 mg./l. Thus, the saturation of cystine in individual urine samples cannot be estimated by comparing the original cystine concentration with a defined cystine solubility curve. It may be more accurately measured as the ratio of original cystine concentration and the directly determined cystine solubility in urine. The estimated assessment of urinary saturation with respect to cystine was shown to deviate from the empirically derived measure from -33 to +44 per cent. In conclusion, cystine is more soluble in urine because of the effects of elecrolytes and macromolecules. Thus, urinary saturation of cystine cannot be estimated from solubility curves but must be empirically derived from the direct assessment of cystine solubility in individual urine samples.
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