ascorbic-acid and Cystinuria

Cystinuria, an autosomal-recessive disorder, is the cause of 1 - 2 % of all kidney stones observed in adults and about 10 % of those observed in infants. Despite increasing understanding of underlying pathomechanisms, patients still form recurrent stones and have to undergo repeated interventions with increasing risk of renal insufficiency. Dietary and medical metaphylaxis may lower the frequency of recurrent stones but are often not practiced. Regular follow-up examinations and optimal therapy significantly enlarge stone-free intervals. This review offers an overview of the underlying pathogenetic mechanisms as well as guidance for diagnosis, monitoring, metaphylaxis and therapy of cystinuria following the recommendations of the Deutsche Gesellschaft für Urologie (DGU) and the European Association of Urology (EAU).

Topics: Adult; Age Factors; Angiotensin-Converting Enzyme Inhibitors; Ascorbic Acid; Captopril; Chelating Agents; Child; Cystinuria; Follow-Up Studies; Humans; Kidney Calculi; Lithotripsy; Penicillamine; Time Factors; Tiopronin; Ureteroscopy

Topics: Ascorbic Acid; Captopril; Cystine; Cystinuria; Humans; Hydrogen-Ion Concentration; Penicillamine; Solubility; Tiopronin; Urine

We investigated ascorbic acid therapy for cystinuria in a study of seven healthy control persons and seven cystinuric patients. The study lasted 9 days. During the first period, we collected 24-h urine specimens from all subjects on 3 consecutive days. Starting on day 4, all were given 5 g ascorbic acid/day for a period of 6 days. On the last 3 days, 24-h urine specimens were again collected. Quantitative amino acid determination was performed using an HPLC method described elsewhere. During ingestion of ascorbic acid, the mean excretion of cysteine by the control group increased from 134.1 to 159 mumol/day, whereas the excretion of cystine decreased from 107.1 to 82 mumol/day. The corresponding values for the cystinuric patients increased from 352.4 to 452.1 mumol/day for cysteine and decreased from 4,131.6 to 3,663.2 mumol/day for cystine. Thus, ascorbic acid seems to have only mild reducing properties in respect to cystine.

Topics: Ascorbic Acid; Chromatography, High Pressure Liquid; Cysteine; Cystinuria; Humans; Oxalates; Oxalic Acid

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.

Topics: Adult; Aged; Ascorbic Acid; Child; Clinical Trials as Topic; Cystinuria; Disease Susceptibility; Dose-Response Relationship, Drug; Female; Humans; Hydrogen-Ion Concentration; Kidney Calculi; Long-Term Care; Male; Middle Aged; Oxalates; Oxalic Acid; Recurrence

Topics: Ascorbic Acid; Cystinuria; Humans

Cystinuria, an inherited disease, is clinically diagnosed by detecting cystine in urine. A colorimetric method using sodium cyanide and sodium nitroprusside is a simple qualitative test used to detect cystinuria. Several colorimetric methods have been proposed for quantitative analysis of cystine; however, we found that none of them were satisfactory because the results were not reproducible. The causes of non-reproducible results were: (1) insufficient reduction time for conversion of cystine to cysteine, and (2) the interference of creatinine. In this report, we present a method to quantitate cystine in urine. We also found that ascorbic acid and ferric chloride, but not zinc chloride, interfered with the color reaction. Using this method, 15 normal urine samples (10 males and 5 females) and 12 cystine stone forming patients' (5 males and 7 females) urine were analyzed. The method was compared to commercially available urine controls. Only captopril showed a dose dependent response and color intensity at 521 nm. Thiola and D-penicillamine showed little effect on cystine determination.

Topics: Adult; Artifacts; Ascorbic Acid; Captopril; Chlorides; Colorimetry; Creatinine; Cyanides; Cysteine; Cystinuria; Dose-Response Relationship, Drug; Female; Ferrous Compounds; Humans; Male; Middle Aged; Nitroprusside; Penicillamine; Reference Values; Reproducibility of Results; Serum Albumin; Tiopronin; Zinc Compounds

Topics: Ascorbic Acid; Cystine; Cystinuria; Humans; Urinary Calculi

Although cystine stones account for 1 to 3 per cent of renal calculi, many of these patients are difficult to manage because of recurrent urolithiasis. Seven cases of homozygous cystinuria are summarized. The evolution to the present treatment of percutaneous extraction and chemolysis appears to be the preferred form of treatment although extracorporeal shock wave lithotripsy (ESWL) may also be utilized. In addition, in vitro experiments were conducted to study the effectiveness of different chelating agents and buffers at different urinary pHs. The effect of cystinuric and noncystinuric urines was also evaluated.

Topics: Acetylcysteine; Adult; Ascorbic Acid; Bicarbonates; Cystine; Cystinuria; Female; Homozygote; Humans; Kidney Calculi; Male; Middle Aged; Penicillamine; Sodium; Sodium Bicarbonate; Tromethamine

A semiquantitative method is presented for the determination of cysteine in urine, based on the formation of a red cysteine/nitroprusside salt. The method is suitable as a rapid test for checking the progress of ascorbic acid therapy of cystinuria and cystine urolithiasis. It guarantees acceptable reproducibility of values and can be easily carried out in any clinical chemical laboratory. With the K2CO3/nitroprusside test described and an additional colorimetric determination of cystine (CN-/nitroprusside), a separate semiquantitative differentiation of cysteine and cystine in fresh (!) urine is possible.

Topics: Ascorbic Acid; Cysteine; Cystinuria; Humans; Monitoring, Physiologic; Urinary Calculi

In this paper a method of semiquantitative cysteine determination is presented, which is based on the formation of a red cysteine-Na-nitroprusside salt. The method is a suitable rapid test for checking the process of ascorbic acid therapy in cystinuria and cystine urolithiasis patients. It guarantees acceptable reproducibility of values and can be easily carried out in every clinicochemical laboratory. With the K2CO3/nitroprusside test described and an additional cystine rapid test (Ni2+/S2O4(2-) tablet reagency) a separate semiquantitative differentiation of cysteine and cystine in fresh (!) urine is possible.

Topics: Ascorbic Acid; Carbonates; Cysteine; Cystinuria; Ferricyanides; Humans; Nitroprusside; Potassium; Urinary Calculi

Long-term results of ascorbic acid monotherapy in four young patients with cystine stone complaints are reported. The therapeutic program is based on the descriptions by Asper and Schmucki, who publicized the method for the first time in 1979. Clinical course observations, renal function checks as well as the excretion of cystine, uric acid and oxalic acid during ascorbic acid therapy of our patient pool will be discussed. Clinical observations made to date indicate that ascorbic acid therapy is a practical, inexpensive prophylaxis for cystine stone patients that is virtually free of side effects.

Topics: Adolescent; Adult; Ascorbic Acid; Child; Cystinuria; Humans; Male; Urinary Calculi

At the beginning of the four chapters on phenomena, analysis, pathophysiology and therapy of cystinuria the essentials of the published literature are summarized. The frequency of cystinuria is in the order of 1:10,000. Besides the cystine lithiasis occurring in nine tenths of all cystinuria patients neurological diseases may also be observed. All commonly applied methods to analyze cystine detect the sum of cystine and cysteine. Cystinuria is characterized by a higher cystine excretion, up to the 100-fold of the normal. Also the concentrations of lysine, arginine and ornithine in the urine of cystinuria patients are elevated, caused by intestinal and renal transport defects. Inevitable damage of renal parenchyma by multiple operations can drastically be reduced by the therapy with D-penicillamine or alpha-mercaptopropionylglycine. The disadvantages of that formation of soluble asymmetric disulfides are the side effects, such as nausea, gastric difficulties and dermatosis, occurring in up to 50% of the patients. Using the especially developed method with HPLC separation and electrochemical detector with a mercury electrode, cystine and cysteine are analyzed simultaneously. In the urine of healthy persons the molar concentration of cysteine is in the same order as cystine. But in cystinuria the cysteine concentration in urine is about a thousand times less than that of cystine. These results are evidence that a shifted redox-equilibrium of cystine-cysteine is also typical of cystinuria. The molar cysteine percentage of cysteine in healthy persons is increased from 30 to 50% by oral ascorbic acid administration. Therefore a vitamin C therapy for cystinuria is developed. 31 cystinuria patients who receive 5 g of vitamin C a day show a decrease in the cystine concentration of about 40%. Up to now, no side effects have been observed. The most obvious sign of the positive effect of the proposed vitamin C therapy for cystinuria is the missing cystine sediment in fresh urine.

Topics: Ascorbic Acid; Cysteine; Cystine; Cystinuria; Humans; Intestinal Absorption; Kidney; Penicillamine; Tiopronin

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.

Topics: Adult; Ascorbic Acid; Cystine; Cystinuria; Dose-Response Relationship, Drug; Female; Humans; Kidney Calculi; Male; Middle Aged; Oxalates; Oxalic Acid; Recurrence; Urinary Bladder Calculi; Urinary Calculi

Topics: Amino Acids; Ascorbic Acid; Body Fluids; Cystinuria; Humans; Nitrogen; Sulfur