From the Guidelines
Thiola (tiopronin) is generally the more appropriate choice for treating existing kidney stones in cystinuria compared to D-penicillamine. Thiola is typically started at 800 mg daily divided into three doses, with maintenance dosing ranging from 600-1200 mg daily based on urinary cystine levels, aiming for levels below 250-300 mg/L. Thiola works by forming soluble complexes with cystine, reducing stone formation and potentially dissolving existing stones. It is preferred because it has a significantly better side effect profile than D-penicillamine, with fewer hypersensitivity reactions, less bone marrow suppression, and reduced risk of nephrotic syndrome. D-penicillamine, while effective, is now considered a second-line agent due to its higher incidence of serious adverse effects including severe skin reactions, taste disturbances, and autoimmune conditions. Both medications should be taken on an empty stomach, and patients should maintain high fluid intake (at least 3 liters daily) and follow a low-sodium, moderate protein diet. Regular monitoring of urinary cystine levels, complete blood counts, liver function, and urinalysis is essential with either medication to ensure efficacy and detect potential adverse effects early, as supported by the American Urological Association guideline 1.
Some key points to consider when treating existing kidney stones in cystinuria include:
- The importance of maintaining high fluid intake to help prevent stone formation and recurrence
- The need for regular monitoring of urinary cystine levels to adjust medication dosing as needed
- The potential for adverse effects with both Thiola and D-penicillamine, and the importance of regular monitoring to detect these early
- The preference for Thiola due to its better side effect profile compared to D-penicillamine, as noted in the guideline 1.
It's also important to note that while other studies discuss the use of D-penicillamine and other treatments for Wilson's disease and other conditions, the most relevant and recent guideline for treating existing kidney stones in cystinuria recommends Thiola as the first-line treatment 1.
From the FDA Drug Label
Tiopronin is a reducing and complexing thiol indicated, in combination with high fluid intake, alkali, and diet modification, for the prevention of cystine stone formation in adults and pediatric patients 9 years of age and older with severe homozygous cystinuria, who are not responsive to these measures alone. In patients who cannot tolerate as much as 1 g/day initially, initiating dosage with 250 mg/day, and increasing gradually to the requisite amount, gives closer control of the effects of the drug and may help to reduce the incidence of adverse reactions. The usual dosage of DEPEN in the treatment of cystinuria is 2 g/day for adults, with a range of 1 to 4 g/day. For pediatric patients, dosage can be based on 30 mg/kg/day
Treating existing kidney stones:
- Thiola (tiopronin) is indicated for the prevention of cystine stone formation, not specifically for treating existing stones.
- D-penicillamine is used in the treatment of cystinuria and can decrease the size of, and even dissolve, stones already formed. Based on the information provided, D-penicillamine appears to be a more appropriate choice for treating existing kidney stones, particularly in cystinuria 2.
From the Research
Treatment Options for Cystinuria
In treating existing kidney stones, particularly in cystinuria, the choice between thiola (tiopronin) and D-penicillamine depends on various factors.
- Thiola has been shown to be effective in reducing cystine excretion and preventing stone formation in patients with cystinuria 3, 4, 5, 6.
- Studies have demonstrated that thiola has fewer side effects compared to D-penicillamine, including less impact on bone marrow, kidney, liver, gastrointestinal tract, and skin 3.
- D-penicillamine, on the other hand, has been associated with serious side effects, albeit it is used in refractory cases to bind cystine in urine 7.
Efficacy of Thiola
- A study published in 1983 found that thiola treatment resulted in only two patients experiencing recurrence of stones due to initial inadequate dose, out of 16 patients with cystinuria treated for 0.5-4 years 3.
- Another study in 2003 showed that tiopronin reduced daily urinary cystine excretion from 901.48 mg to 488.60 mg in patients with cystinuria, with the therapy being tolerated well 4.
- A long-term study published in 1995 found that the rate of stone formation during tiopronin treatment was reduced by 60% compared to the pretreatment period, with the frequency of active stone removal reduced by 72% 5.
Comparison with D-penicillamine
- A study from 1975 found that thiola was more effective than D-penicillamine in dissolving L-cystine, with good tolerance and no serious effects observed 6.
- Overall, the evidence suggests that thiola (tiopronin) is a more appropriate choice than D-penicillamine for treating existing kidney stones in patients with cystinuria, due to its efficacy and lower side effect profile 3, 4, 5, 6.