1981 Volume 72 Issue 2 Pages 221-236
Tiopronin (α-mercaptopropionylglycine) not only prevents the stone formation, but also dissolves stones in cystinurics by initiating mixed thiol-disulfide exchange reactions. The treatment, however, requires permanent drug administration. The dosage of tiopronin should be kept as small as possible. For that purpose the protocol for the prophylaxis should be separated from that for the litholysis.
Twenty-two cystinuric stone formers were treated with the following protocol since 1973. The dosage of tiopronin was adjusted to maintain the 24 hour urinary cystine level at less than 250mg/l for the prevention of the recurrent stone formation, and at less than 100mg/l for dissolution of stones. Patients were also advised to drink liquids to keep the daily urinary output over 2 liters for adults and as much as possible for children. On the other hand, adult patients whose urinary cystine excretion were below 400mg/day were treated by hydration only without tiopronin. Patients received this treatment with the protocol (17 patients treated with tiopronin and 5 with hydration only) for 19 to 72 months (50 months on the average). The results are as follows:
1) Out of 17 recurrent stone formers treated with tiopronin, calculi were completely or partially dissolved in 6 patients, recurrent stone formation was prevented in 5, and the treatment failed in 7 (stone recurred after once dissolved in one patient).
2) Among those 7 failures, 5 patients did not take tiopronin regularly and the dosage of tiopronin was too small in one patient. In the last patient, her cystine stone was covered with a shell of calcium phosphate, which was probably formed by alkaline urine and hyperuricosuria.
3) Pure cystine stones were dissolved by maintaining urinary cystine level at 150mg/l, when urinary output was kept 2 liters or more. All of stones which were only partially dissolved, however, were mixed cystine calculi.
4) Of 5 patients treated with hydration only for 3 to 6 years, none had recurrent stone formation except one case with only one colicky attack.
5) The analysis of the stones obtained from these 20 patients revealed that 65% (13 cases) were pure cystine stone, 25% (5 cases) were mixed cystine with calcium phosphate or struvite, and 10% (2 cases) were non cystine stone. The result indicates that urinary pH should be kept below 7, although alkaline therapy is useful in the treatment of pure cystine calculi.
These results showed that our protocol is satisfactorily effective for treating cystinuric stone formers. It is strongly suggested that the stone probably consists of matter other than cystine, when this protocol is not satisfactory.
