The Effect of Sodium Intake on Cystinuria with and without Tiopronin Treatment

Abstract

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 μmol (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.

CUA guideline on the evaluation and medical management of the kidney stone patient ‒ 2016 update

“…136,137 Sodium restriction is advised for all patients with cystinuria because sodium and cystine excretion are associated. 138 In small studies, sodium restriction significantly decreased cystine excretion, [138][139][140] reflecting this coupling of cystine to parallel sodium transport in the kidney. Elevated dietary protein is associated with increased urinary cystine 141 and a reduction in overall protein intake can decrease urinary cystine levels.…”

Cystinuria—a urologist's perspective

“…38,39,41 Traditionally, night was thought to be when most patients were at highest risk of cystine supersaturation. 42 However, studies have not shown a diurnal difference in the number of discrete super saturation episodes. 43 We ask our patients to complete a diary describing fluid intake and our special ist dietician provides tailored advice regarding fluid manage ment depending on each patient's individ ual circum stances.…”

“…14,42,47 Lowering sodium intake by 3.5 g per day decreases cystine excretion by 156 mg per day, which might maintain soluble cystine levels in the patient. 48 In the UK, the average salt intake per day is 8.6 g (3.4 g sodium), and 75% of this salt intake comes from processed foods.…”

New horizons in the management of patients with cystinuria

“…The most common way of alkalization that is otherwise used today is administration of potassium citrate. An increased urine pH can be also accomplished by sodium bicarbonate, but the additional load of sodium with this form of alkalization might have negative effects due to increased excretion of cystine [34].…”