Cystinuria: Effect of D-Penicillamine on Plasma and Urinary Cystine Concentrations

Crawhall, J. C.; Thompson, C. J.

doi:10.1126/science.147.3664.1459

Cited by 39 publications

(7 citation statements)

References 8 publications

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“…A similar reaction occurs in cystinuric patients treated with D-penicillamine. In these patients the plasma and urinary cystine concentration decreases as the mixed disulfide of penicillamine and cysteine appears (35). Difficulty in enforcing stringent dietary regulations in an anorectic child and lack of quantitation of fecal sulfur excretion precluded a more formal balance study in our patient.…”

Section: Resultsmentioning

confidence: 99%

Cystinosis. Intracellular cystine depletion by aminothiols in vitro and in vivo.

Thoene¹,

Oshima²,

Crawhall³

et al. 1976

J. Clin. Invest.

315

164

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Section: Resultsmentioning

confidence: 99%

Cystinosis. Intracellular cystine depletion by aminothiols in vitro and in vivo.

Thoene¹,

Oshima²,

Crawhall³

et al. 1976

J. Clin. Invest.

315

164

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“…The effect of penicillamine therapy on the blood and urinary concentrations and on the renal clearances of these amino acids and of cysteine-penicillamine and penicillamine disulfide is also reported. Some of these results have been the subject of a preliminary communication (7).…”

Section: Introductionmentioning

confidence: 99%

The Renal Clearance of Amino Acids in Cystinuria*

Crawhall¹,

Scowen²,

Thompson³

et al. 1967

J. Clin. Invest.

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Summary. The renal clearance of cystine, lysine, ornithine, arginine, and glycine has been compared with the simultaneously determined glomerular filtration rate in nine cystinuric patients. Five were studied before and after stabilization on penicillamine therapy, two were studied only while taking penicillamine, and two were studied only in the absence of penicillamine administration. The renal clearances of cysteine-penicillamine and of penicillamine disulfide were also determined in the patients who were taking the drug.Amino acids were determined by quantitative ion exchange chromatography, and the reliability of the method has been evaluated in terms of its reproducibility and of the recovery of known amounts of amino acids added to plasma and to urine. The plasma levels of cystine and of the basic amino acids were less than normal in all the patients. Cysteine-penicillamine and penicillamine disulfide were cleared by the kidney at rates similar to that of cystine. Two of the patients had glycine clearances that were considerably above the normal value. The renal clearance of cystine exceeded the glomerular filtration rate in six of the nine patients. The results form a continuum from values approximately equal to the glomerular filtration rate to values about twice this amount. The renal clearances of cystine and of the basic amino acids vary independently of one another in the disease.The significance of these results is discussed in terms of the nature of the renal tubular transport defect that underlies the disorder.

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“…A disulfide bond is formed between the cysteine monomer and the drug, as opposed to forming an insoluble cystine dimer. D-penicillamine is modestly effective, at best, and is frequently associated with the side effects of nephrotic syndrome, dermatitis, and pancytopenia [26][27][28][29]. αmercaptopropionylglycine acts via a sulfhydryl group that has binding affinity for cysteine to produce a similar solubilizing effect, and seems to be more well tolerated by patients than D-penicillamine (64.7% with side effects compared with 83.7% on D-penicillamine) [30].…”

Section: Organosulfur Drugs and Crystal Inhibitorsmentioning

confidence: 99%

Alpha lipoic acid as a novel therapeutic approach to cystinuria

Wiener

Chi

Stoller

2018

Expert Opinion on Orphan Drugs

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Introduction: Cystinuria is a rare form of kidney stone disease inherited through mutations in the cystine transporter genes SLC3A1 and SLC7A9. Patients suffer from frequent and painful renal cystine calculus formation necessitating repeated radiation exposure, hospitalizations and surgical interventions. Available dietary and pharmacologic managements are burdensome to patients due to the sheer volume of pills and fluid that must be consumed and display limited efficacy. Areas Covered: The epidemiology, pathophysiology, and currently available options for dietary and pharmacological management including hyperhydration, modification of urinary pH, organosulfur drugs and crystal Inhibitors are reviewed. A novel drug in clinical trials, alpha lipoic acid (ALA), is presented and its hypothesized mechanism of action reviewed. Expert Opinion: A novel potential therapy, alpha lipoic acid, has been strikingly effective when used in a knockout mouse model. This compound is available over the counter as a food supplement, has been used in multiple human trials for other disease processes and has been shown to be safe and well tolerated. The promise of ALA is to reduce the burden of medications, stone events, surgical interventions, and financial concerns in cystinuric patients.

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Cystinuria: Effect of D-Penicillamine on Plasma and Urinary Cystine Concentrations

Abstract: Administration of penicillamine reduced the concentration of cystine in the plasma and urine of patients with cystinuria; renal clearance of cystine, lysine, and arginine remained unchanged. Cysteine-penicillamine disulfide and penicillamine disulfide were detected in the plasma.

Cited by 39 publications

References 8 publications

Cystinosis. Intracellular cystine depletion by aminothiols in vitro and in vivo.

Cystinosis. Intracellular cystine depletion by aminothiols in vitro and in vivo.

The Renal Clearance of Amino Acids in Cystinuria*

Alpha lipoic acid as a novel therapeutic approach to cystinuria

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