As with many other
amino acids the transport of
cystine across the tubular epithelium is coupled to a parallel transport of
sodium. We have studied the effect of a
sodium-restricted diet on the urinary excretion of
cystine in 13 patients with
cystinuria, 7 of whom were treated with the SH compound
tiopronin (2-mercaptopropionylglycine). Five of the patients with
tiopronin and 5 without were also given
sodium bicarbonate. The patients were instructed to follow a
sodium-restricted diet during three periods of 2 weeks each. Four levels of
sodium intake were obtained including the preexperimental unrestricted diet. The average 24-hour excretion of free
cystine increased by 3.1 mumol (0.75 mg) for each millimole increase in urinary
sodium (p < 0.001). There was a greater
sodium-related increase in excretion of
cystine among patients without
tiopronin treatment compared with the group with
tiopronin (p < 0.01). Withdrawal of
sodium bicarbonate resulted in a decrease in the 24-hour
cystine excretion (p < 0.05). In the patients treated with
tiopronin the excretion of the mixed
disulfide increased with increasing urinary
sodium (p < 0.05) suggesting a
sodium-dependent active tubular reabsorption of this compound as well. We conclude that in spite of a defective proximal tubular reabsorption of
cystine in
cystinuria the reabsorption can be increased by restricting the intake of
sodium. This effect of
sodium may have clinical consequences for some cystinuric patients.