Cystinuria in Children

Pavanello, Luigi; Rizzoni, Gianfranco; Dussini, N; Zacchello, G; Passerini, Giorgia; Tasca, A; Pagano, Federica

doi:10.1159/000473204

Cited by 14 publications

(6 citation statements)

References 8 publications

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“…In several reports on patients treated with tiopronin the 24-hour cystine excretion was used for dose adjust ment [7][8][9][10]24], From a clinical point of view the main pathophysiologic event in cystinuria is the crystallization of cystine from the supersaturated urine, and the subse quent formation of stones. The objectives of the stone preventing therapy in cystinuria are thus to avoid super saturation, and in our opinion the therapeutic effect is better followed by measuring the cystine concentration than the 24-hour excretion.…”

Section: Dose Adjustment By Monitoring the Concentration O F Cystinementioning

confidence: 99%

Urinary Excretion of Free Cystine and the Tiopronin-Cysteine-Mixed Disulfide during Long-Term Tiopronin Treatment of Cystinuria

Lindell

Denneberg

Jeppsson

1995

Nephron

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We report the results of a biochemical evaluation of long-term treatment of cystinuria with the SH compound tiopronin (2-mercaptopropionylglycine). The effects of tiopronin were studied by monitoring the urinary excretion of free cystine and the mixed disulfide between tiopronin and cysteine. Thirty-one patients with homozygous cystinuria were treated with tiopronin for 0.4-12 years (mean 7.8 years). The urinary concentration of free cystine was used to adjust the tiopronin dose. In 28 of the 31 patients a mean urinary cystine concentration of less than 1,200 μmol/1 (288 mg/l) was achieved with the final dose. The final daily doses of tiopronin ranged from 250 mg (1.5 mmol) to 3,000 mg (18.4 mmol; mean 1,540 mg; 9.4 mmol). In a majority of the patients the treatment reduced the 24-hour urinary free cystine excretion effectively, on average by 0.61 μmol (0.15 mg)/mg of tiopronin administered. No changes in the efficacy of tiopronin over time were observed, and the frequency of adverse effects was acceptable. To evaluate the effects of tiopronin on the metabolism of cystine we calculated the total urinary excretion of cystine as the sum of free cystine and the amount of cystine corresponding to the cysteine content of the tiopronin-cysteine disulfide. At low doses of tiopronin there was an increase in urinary excretion of the mixed disulfide as well as of total cystine, whereas higher doses were followed by an unexpected decrease in the urinary excretion of these compounds. We conclude that long-term treatment with tiopronin in cystinuria effectively reduces the urinary excretion of free cystine. Monitoring urinary cystine concentration is necessary to achieve adequate individualized doses of tiopronin. Assessment of the mixed tiopronin-cysteine disulfide and the urinary excretion of total cystine shows that tiopronin may interfere with cystine metabolism in a more complex way than through a simple disulfide exchange reaction with urinary cystine.

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Section: Dose Adjustment By Monitoring the Concentration O F Cystinementioning

confidence: 99%

Urinary Excretion of Free Cystine and the Tiopronin-Cysteine-Mixed Disulfide during Long-Term Tiopronin Treatment of Cystinuria

Lindell

Denneberg

Jeppsson

1995

Nephron

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“…Other reports also describe nephrotic syndrome in cystinuria patients treated with tiopronin [1,3,[11][12][13]15]. Ferraccioli et al reported the biopsy findings of six patients who developed nephrotic syndrome during treatment with tiopronin [6].…”

Section: Discussionmentioning

confidence: 99%

Nephrotic syndrome occurring during tiopronin treatment for cystinuria

et al. 2010

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Cystinuria is an autosomal recessive disorder characterized with abnormal tubular reabsorption of cystine and dibasic amino acids leading to cystine urolithiasis. The classical form is caused by mutations in the SLC3A1 gene (OMIM 220100). The cornerstone of the treatment is high hydration and alkalization of the urine to achieve urine pH between 7.0 and 7.5, at which point, cystine solubility in the urine is optimal. These measures very often fail, and thus addition of sulfhydryl agents like penicillamine and tiopronin (mercaptopropionyl glycine) is recommended. Herein, we report a 3-year-old boy with cystinuria resulting in recurrent nephrolithiasis requiring surgery and extracorporeal shock wave lithotripsy. Nine months after introduction of tiopronin, the boy manifested generalized edema, oliguria, and biochemical indices of nephrotic syndrome. Tiopronin was withdrawn, and the boy was given only supportive treatment. Within 10 days, he entered into clinical and biochemical remission. Pediatricians should be aware of this adverse effect of tiopronin, and therefore, testing of the urine with strips or sulfosalicylic acid at least once weekly at home may be very helpful for early detection of proteinuria.

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“…Cystinuria is the commonest metabolic disorder to cause stones in children. Treatment and recurrence prevention are once again based on the following principles, each of which will receive varying emphasis, depending on age and weight of the child (PAVANELLO et al 1981). 1.…”

Section: Dietary and Medical Treatment Of Cystinuriamentioning

confidence: 99%