The Impact of Diet on Urinary Risk Factors for Cystine Stone Formation.

Despite the importance of dietary management of cystinuria, data on the contribution of diet to urinary risk factors for cystine stone formation are limited. Studies on the physiological effects of diet on urinary cystine and cysteine excretion are lacking. Accordingly, 10 healthy men received three standardized diets for a period of five days each and collected daily 24 h urine. The Western-type diet (WD; 95 g/day protein) corresponded to usual dietary habits, whereas the mixed diet (MD; 65 g/day protein) and lacto-ovo-vegetarian diet (VD; 65 g/day protein) were calculated according to dietary reference intakes. With intake of the VD, urinary cystine and cysteine excretion decreased by 22 and 15%, respectively, compared to the WD, although the differences were not statistically significant. Urine pH was significantly highest on the VD. Regression analysis showed that urinary phosphate was significantly associated with cystine excretion, while urinary sulfate was a predictor of cysteine excretion. Neither urinary cystine nor cysteine excretion was affected by dietary sodium intake. A lacto-ovo-vegetarian diet is particularly suitable for the dietary treatment of cystinuria, since the additional alkali load may reduce the amount of required alkalizing agents.

[Modulation of the phenotypic expression in the patient with cystinuria: influence of therapeutic intervention and diet]. / Modulacion de la expresion fenotipica del paciente con cistinuria: influencia de la intervencion terapeutica y de la dieta.

OBJECTIVES: The final phenotype of patients with cystinuria depends on the absence or molecular defect, more or less acute, of the transport of cystine and dibasic aminoacids, and, also on environmental factors. The objective of this work is to study the effect of the modulation of some environmental factors (urinary pH, intake of liquids, pharmacological treatment and, specially, diet) on the final phenotype of the patient with cystinuria. METHODS: We study 45 patients with cystinuria (25 men and 20 women), 42 relatives (15 men and 27 women) and 90 unrelated controls. Anthropometric, clinical (personal and familiar history of urinary infections, colics and calculi expulsion), biochemical (microscopy analysis of urine and urinary aminoacids cuantification) and life style (diet and medical treatment) variables were obtained. Statistical analysis was performed using tests to compare means and frequencies and, also, logistic regression and multivariate analysis. RESULTS: Of the 45 patients with cystinuria, only 20% showed cystine cristalls in urine, the rest of the phenotypical manifestations of cystinuria were found with the same prevalence as in relatives and in the control group. 50% of the patients did not undergo any therapeutic intervention; of these, only 50% were effective. In patients with cystinuria, the presence of cystine cristalls was associated with a diet rich in meats and poor in milk products (p < 0.05). Meat consumption also tend to associate with a higher risk of urinary infections, meanwhile the stone expulsion showed a negative tendance with a diet rich in phytate. The elevate consumption of oranges and mandarins was the variable of the diet which was more associated with urinary aminoacids concentrations, specially with lower levels of lysine and arginine (p < 0.05). CONCLUSIONS: Some components of the diet, in addition to standard treatment, modulate the phenotypical manifestations of cystinuria.

Treatment of cystinuria.

Cystine urolithiasis is the only clinical expression of cystinuria, an autosomal recessive genetic defect of the transepithelial transport of cystine and other dibasic amino acids in the kidney. Stones form due to the increased excretion of cystine, which is poorly soluble at normal urine pH. Cystine stones are often resistant to extracorporeal shock wave lithotripsy, so that percutaneous surgery or ureteroscopy are the preferred techniques of stone extraction. Medical preventative treatment is based on high diuresis (>/=1.5 l/m(2) per day) well distributed throughout the day and night, and urine alkalinization up to pH 7.5 by means of sodium bicarbonate and/or potassium citrate. When these basal measures are ineffective at preventing stone recurrence or dissolving pre-existing stones, sulfhydryl agents such as D-penicillamine or tiopronin, which form highly soluble mixed disulfides with cystine moieties, are to be added to urine dilution and alkalinization, especially when cystine excretion is in excess of 750 mg/day (3 mmol/day). Frequent clinical and ultrasound follow-up is needed to encourage patient compliance and assess efficacy and tolerance of treatment.

The effect of sodium intake on cystinuria with and without tiopronin treatment.

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.

Effect of a low sodium diet on urinary elimination of cystine in cystinuric children.

Restriction of sodium intake has been shown to decrease urinary elimination of cystine in adult subjects with cystinuria. This simple therapeutic recommendation may be particularly useful in pediatric patients whose compliance with high fluid ingestion and repeated doses of alkali is usually poor. We studied the effect of sodium intake in 5 cystinuric children (3 males) aged 5.9-9.3 years. Urinary excretion of cystine (means +/- SD) was determined at the end of two sequential 1-week periods in which sodium content of diet was modified. Reduction of sodium intake brought about significant decreases in natriuresis (6.0 +/- 2.1 vs. 1.5 +/- 0.5 mEq/kg/day, p < 0.03) and urine cystine concentration (328.0 +/- 190.7 vs. 14.1 +/- 7.4 mg/l, p < 0.02) while urine volume output remained unchanged (58.0 +/- 36.0 vs. 70.3 +/- 33.0 ml/kg/day). These findings confirm that elimination of cystine is highly influenced by sodium intake in cystinuric children and suggest that a low sodium diet may play a key-role in the treatment of pediatric patients with cystinuria.

Dietary restriction of sodium as a means of reducing urinary cystine.

We assessed 5 patients with recurrent cystine urolithiasis before and after implementation of a low sodium diet. This diet led to a significant decrease in the 24-hour urinary excretion of sodium and cystine. Dietary restriction of sodium should be an important component of the therapeutic strategy of patients with cystinuria.

The effect of dietary protein on cystine excretion in patients with cystinuria.

Seven patients with homozygous cystinuria were studied on a metabolic ward to determine the effect of dietary manipulation on urinary cystine excretion. Isocaloric diets were calculated based on body weight and activity. Balance studies were performed for 5 days on a low protein diet (9.4 +/- 1.0% total calories) with equal amounts of animal and plant protein sources and an additional 5 days on a high protein (27 +/- 3.0% of total calories) with 70% animal protein. A significant (p less than 0.01) decrease in the excretion of 1/2-cystine, histidine, 3-methylhistidine, 1-methylhistidine, lysine, and ornithine plus arginine occurred on the low protein diet. The mean excretion of 1/2-cystine on the high protein diet was 6.13 +/- 1.48 mMoles per 24 hours which decreased to 4.89 +/- 1.06 mMoles per 24 hours on the low protein diet (p less than 0.001). Thirty seven percent of urine collections during the study were less than 2 liters/24 hours despite the fact that patients were encouraged to drink enough fluid to make 3 liters of urine/24 hours. For patients whose customary diet is high in animal protein, a more vegetarian diet may significantly reduce urinary cystine excretion. Cystine excretion in patients with cystinuria may be significantly different from day to day if animal protein consumption is variable.