α-Lipoic Acid (ALA) Improves Cystine Solubility in Cystinuria: Report of 2 Cases.

Cystinuria is an autosomal recessive disorder characterized by excessive urinary excretion of cystine, resulting in recurrent cystine kidney stones, often presenting in childhood. Current treatment options for cystinuria include dietary and/or fluid measures and potassium citrate to reduce cystine excretion and/or increase solubility. Tiopronin and D-penicillamine are used in refractory cases to bind cystine in urine, albeit with serious side effects. A recent study revealed efficacy of nutritional supplement α-lipoic acid (ALA) treatment in preventing kidney stones in a mouse model of cystinuria. Here, we report 2 pediatric patients (6 and 15 years old) with cystinuria who received regular doses of ALA in addition to conventional therapy with potassium citrate. Both patients tolerated ALA without any adverse effects and had reduced frequency of symptomatic and asymptomatic kidney stones with disappearance of existing kidney stones in 1 patient after 2 months of ALA therapy. ALA treatment markedly improved laboratory markers of cystine solubility in urine with increased cystine capacity (-223 to -1 mg/L in patient 1 and +140 to +272 mg/L in patient 2) and decreased cystine supersaturation (1.7 to 0.88 in patient 1 and 0.64 to 0.48 in patient 2) without any changes in cystine excretion or urine pH. Our findings suggest that ALA improves solubility of cystine in urine and prevents stone formation in patients with cystinuria who do not respond to diet and citrate therapy.

Cistinuria: la recurrencia de lo excepcional / Cystinuria: the recurrence of the exceptional

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[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.

[Beneficial effect of angiotensin converting enzyme inhibitor treatment in severe cystine urolithiasis]. / Korzystny efekt leczenia inhibitorem enzymu konwertujacego angiotensyne w ciezkiej cystynowej kamicy nerkowej.

Cystinuria is an autosomal recessive defect in transepithelial transport of dibasic amino acids (e.g. cystine) which involves the proximal canaliculi, small intestine and central nervous system. It is the least common cause of nephrolithiasis, accounting for 1 to 3% of renal calculi. The natural course of the disease, characterised by recurrent stone formation, can frequently lead to renal failure, if left untreated. Until recently, treatment of cystinuria has been limited to symptomatic management including intensive hydration and urine alkalinisation. Different drugs that react with cystine to form soluble complexes have been used but their efficacy remains questionable. We present the case of a 6-year-old boy with severe, recurrent cystine urolithiasis treated with captopril. The diagnosis of cystine urolithiasis was established after a 3-year course of clinically apparent nephrolithiasis, characterised by stone passage. At the age of 5 years he underwent lithotripsy and nephrolithotomy for removal of staghorn calculi. Since then treatment with citrate and magnesium supplementation combined with captopril was introduced. After a follow-up of 12 months the patient remained stone-free. Urinary cystine decreased from 230 to 136 mg per gram creatinine. We conclude that captopril can be useful in the treatment of cystine urolithiasis in children.

[Possibilities and limits in the treatment of cystine calculus diathesis with high-dose ascorbic acid. Results of a combined study with 17 patients]. / Möglichkeiten und Grenzen bei der Behandlung der Zystinsteindiathese mit hochdosierter Ascorbinsäure. Ergebnisse einer Verbundstudie mit 17 Patienten.

17 cystine stone patients were treated with high doses of ascorbic acid (5 g p. d.). During the observation period, a total of only two natural passages of cystine stones could be observed. For five patients the therapeutic strategy was altered because the recurrence rate did not change and the cystine concentration in the urine was enhanced. One mixed calcium-oxalate/cystine stone had to be resected. In this case as well as on the occasion of further medical check-ups of other patients, an increased risk of calcium-oxalate stone formation was signalled by an enhanced oxalic-acid concentration in the 24-hour urine. Changes in blood serum and impairment in hepatic and renal functions were not observed. With three patients, the therapy had to be interrupted because of gastritis symptoms. The use of high-dose ascorbic acid therapy is recommended and is continued. In special cases, an additive of low do ses of alpha-mercaptopropionyl-glycine is recommended.

[Personal experiences in the long-term treatment of cystine lithiasis with high-dose ascorbic acid]. / Unsere Erfahrungen bei der Langzeitbehandlung des Zystinsteinleidens mit hochdosierter Askorbinsäure.

We report on our experience with 9 cystine-lithiasis patients who were treated with large doses of ascorbic acid (5 g/day) for periods ranging from 6-27 months. We observed recidive lithogenesis in only 3 patients during this time. The influence of ascorbic acid on the excretion of cystine and oxalate in the urine is discussed. A lack of side effects and the significantly lower frequency of recidivation justify the further use of ascorbic as an alternative medication in cystine lithiasis.

Cystine calcium bladder calculus in a 2-year-old child.

We report on a 2-year-old child who presented with urinary tract infection and a large solitary bladder calculus. Dietary history indicated an intake of 2 gm. calcium with supplemental vitamin D daily. Urinary amino acid analysis revealed cystinuria. The high dietary intake of calcium and vitamin D may have precipitated early cystine calcium stone formation.

[Cystine stone therapy with mercapto-propyonyl-glycine (MPG) (Thiola) (author's transl)]. / Cystinsteintherapie mit Mercaptopropyonylglycin (MPG) (Thiola)

Six patients with recurrent cystine stones and cystinuria were treated with MPG. Three patients were treated for 3 years and 3 patients for 6 months. A relatively high dosage resulted in a reduction of the cytinuria. Since MPG has almost no side effects it represents a valuable aid in the treatment of cystine stones.