Cystine-stone therapy with alpha-mercapto-propionylglycine

Abstract

The aim of therapeutic management in cystinuria is simply to keep the urinary cystine concentration less than supersaturation and thus to prevent cystine precipitation and subsequent stone formation. However, the results in clinical experience with cystinuria treatment continue to be poor. The most promising form of therapy at present is changing cystine to a chemically more soluble form. Until now, treatment has relied primarily on d-penicillamine. However, the drug has serious side effects that limit its application. MPG is a newly developed drug, promising higher effectiveness and lack of toxic side effects. From 1970 to 1983, 38 female and 61 male cystinuric stone formers with a mean age of 36 years have been treated with MPG. Of these 99 patients, 42 form the basis of a report on long-term follow-up, i.e., MPG treatment for a period greater than 3 years. The dose of MPG required was adjusted to the urinary cystine level, which should be less than 100 mg/d if calculi are to be prevented. The results were as follows: 1) There was no recurrent stone formation except at the immediate onset of the MPG therapy when 14 of the 42 patients continued to pass small calculi. However, in these patients this must be attributed to their failure to follow the MPG regimen appropriately in the early days of the therapy. 2) The routinely performed tests were normal through the years, and there were no major side effects necessitating withdrawal of the drug. 3) Unfortunately, continued use of MPG during this 10-year period resulted in a slight loss of effectiveness in 27 of the 42 patients. In these patients the dosage had to be increased stepwise from 600 to 2,000 mg/d. 4) After a dosage increase to finally 2,500 mg/d after a treatment period of 9 years, the cystine excretion in only one patient showed no further response and thus this patient is the only treatment failure. Because of its high effectiveness and lack of toxicity MPG currently should be the treatment of choice in cystinuric stone-forming patients.