UNIGE document Scientific Article
previous document  unige:47576  next document
add to browser collection
Title

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

Authors
Rozen, R
Dziarmaga, A
Goodyer, P
Published in Molecular Genetics and Metabolism. 2003, vol. 80, no. 4, p. 419-25
Abstract 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.
Keywords AdolescentAge FactorsChemical PrecipitationChildChild, PreschoolCystine/analysis/chemistryCystinuria/complications/drug therapy/geneticsDose-Response Relationship, DrugHumansInfantKidney Diseases/etiology/urineLithiasis/etiology/urinePenicillamine/pharmacologyReference ValuesSuccimer/pharmacologyTiopronin/pharmacologyUrine/chemistry
Identifiers
PMID: 14654355
Full text
Article (Published version) (432 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Citation
(ISO format)
PARVEX, Paloma Maria et al. 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. In: Molecular Genetics and Metabolism, 2003, vol. 80, n° 4, p. 419-25. https://archive-ouverte.unige.ch/unige:47576

158 hits

0 download

Update

Deposited on : 2015-03-04

Export document
Format :
Citation style :