Document Detail

Studies of urinary cystine precipitation in vitro: ontogeny of cystine nephrolithiasis and identification of meso-2,3-dimercaptosuccinic acid as a potential therapy for cystinuria.
MedLine Citation:
PMID:  14654355     Owner:  NLM     Status:  MEDLINE    
Children with fully recessive (Type I/I) cystinuria have a high risk of stone formation in the first decade of life. To assess the tendency for cystine to precipitate in individual urine samples, we developed an in vitro assay in which radiolabelled cystine (4mM) was dissolved in urine at 37 degrees C after alkalization to pH 10. Samples were then brought to pH 5, cooled, and centrifuged. The % decrease in supernatant cpm was used as a measure of cystine precipitation (CP). CP varied widely among normal children (74%+/-34) whereas variability of repeated determinations on a single adult individual was modest (64%+/-3.3). The assay was used to compare various potential therapies for cystinuria. Precipitation of exogenous cystine from normal urine was strongly inhibited by addition of D-penicillamine (CP: 8%+/-3) or dimercaptosuccinic acid (DMSA) (CP: 5%+/-1), at urinary concentrations attained by standard oral doses of each drug. Mercaptopropionylglycine (MPG) was moderately effective (CP: 43%+/-9), whereas captopril was a weak inhibitor (CP: 63%+/-12). Precipitation of endogenous cystine (2191 micromol/L) from a cystinuric patient showed that DMSA and D-penicillamine were again highly effective compared to the other agents. In addition DMSA and penicillamine added to the same patient's urine reduced the free cystine by 50% (as measured by automated amino acid analyzer) whereas MPG and captopril had no effect. In conclusion, DMSA is comparable to D-penicillamine as an in vitro inhibitor.
P Parvex; R Rozen; A Dziarmaga; P Goodyer
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Molecular genetics and metabolism     Volume:  80     ISSN:  1096-7192     ISO Abbreviation:  Mol. Genet. Metab.     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2003-12-05     Completed Date:  2004-09-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9805456     Medline TA:  Mol Genet Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  419-25     Citation Subset:  IM    
Department of Nephrology, Geneva Children's Hospital, Geneva, Switzerland.
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MeSH Terms
Age Factors
Chemical Precipitation
Child, Preschool
Cystine / analysis*,  chemistry
Cystinuria / complications,  drug therapy*,  genetics
Dose-Response Relationship, Drug
Kidney Diseases / etiology,  urine*
Lithiasis / etiology,  urine*
Penicillamine / pharmacology
Reference Values
Succimer / pharmacology*
Thiopronine / pharmacology
Urine / chemistry
Reg. No./Substance:
1953-02-2/Thiopronine; 304-55-2/Succimer; 52-67-5/Penicillamine; 56-89-3/Cystine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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