Canine cystinuria: an extended study on the effects of 2-mercaptopropionylglycine on cystine urolithiasis and urinary cystine excretion.

A clinical study covering 1 to 6 years was undertaken during which 25 cystinuric dogs were orally treated with 2-mercaptopropionylglycine (2-MPG). The drug was effective at dissolving uroliths at a dose of approximately 40 mg kg-1 body weight. In 15 dogs with bladder uroliths, complete urolith dissolution was achieved on 9/17 occasions (53%). When 2-MPG was administered prophylactically at 30 mg/kg body weight, uroliths did not reform in 14 dogs (56%). In four dogs, uroliths re-formed during treatment, but dissolved when the dose of 2-MPG was raised to 40 mg kg-1 body weight. Six dogs were surgically treated, and in two of these animals the uroliths were found to consist of magnesium ammonium phosphate. Euthanasia was performed on six dogs during the study; three because of recurrent uroliths with urethral obstruction, and three because of aging. In one dog, uroliths were present in the bladder throughout the study. The purpose of the study was to propose a new strategy for individual treatment of cystinuric dogs. This was accomplished by measuring the urinary free cystine concentration and the mixed cysteine-2-MPG disulphide in a subgroup of 15 of the 25 dogs. To evaluate cystine excretion, morning samples of urine were used, and the cystine concentration was related to the creatinine concentration. For dose adjustment it was difficult to evaluate the effect of 2-MPG on urinary cystine excretion, especially when cystine uroliths were present. However, this variable was studied in order to identify dogs with a strong tendency for urolith formation during 2-MPG treatment. In some cases, urinary cystine excretion returned to normal with time, and in three dogs, 2-MPG treatment could be stopped after 1.5 to 3.5 years. In spite of no further treatment, urinary cystine was almost undetectable up to 2 years later, and the dogs did not develop any new uroliths. It was concluded that 2-MPG is a satisfactory alternative treatment for cystinuric dogs. It has a good prophylactic effect, shown as a change in the rate of urolith formation from on average 6 months before to 17 months during 2-MPT treatment. The drug was shown to have few side effects, and the dog owner drug compliance can be followed by measurement of the mixed 2-MPG-cysteine disulphide.