From the Guidelines
No, uricase therapy, such as rasburicase, does not aggravate kidney stones, specifically those composed of uric acid; in fact, it can help prevent or treat them. This is because rasburicase works by converting uric acid to allantoin, which is 5-10 times more soluble in urine than uric acid itself, thereby reducing the risk of uric acid precipitation and stone formation in the kidneys. The primary concern with uric acid stones is often the low urinary pH rather than hyperuricosuria, as noted in the medical management of kidney stones guideline 1. However, the use of uricase therapy directly addresses the issue of uric acid concentration, which is a key factor in stone formation.
Key points to consider:
- Rasburicase is administered at a specific dose, typically 0.2 mg/kg as a single intravenous infusion over 30 minutes, though treatment protocols may vary based on clinical circumstances.
- The mechanism of action of rasburicase, converting uric acid to allantoin, makes it beneficial for patients with uric acid kidney stones by reducing the concentration of poorly soluble uric acid in the urine.
- Patients receiving rasburicase should maintain adequate hydration to help flush the allantoin through the kidneys, which is crucial for preventing stone formation.
- The medical management of kidney stones, as per the AUA guideline 1, suggests that first-line therapy for patients with uric acid stones is alkalinization of the urine with potassium citrate, but it does not address the direct conversion of uric acid to a more soluble form as a preventive measure.
In clinical practice, the use of uricase therapy like rasburicase can be seen as a beneficial approach for managing uric acid kidney stones, given its mechanism of action and the fact that it does not exacerbate the condition, unlike what might be inferred from the management of hyperuricosuria with allopurinol in patients with low urinary pH 1.
From the Research
Uricase Therapy and Kidney Stones
- Uricase therapy, such as rasburicase, is used to treat hyperuricemia by converting uric acid to allantoin, a more water-soluble compound that can be easily excreted by the kidneys 2, 3, 4.
- The use of rasburicase has been shown to be effective in reducing serum uric acid levels and improving renal function in patients with acute kidney injury and hyperuricemia 2, 5.
- However, there is limited information on the specific effect of uricase therapy on kidney stones, particularly those composed of uric acid.
- One study suggests that rasburicase may be able to fragment renal calculi and promote relief of obstructive uropathy, potentially resolving renal failure 2.
- Another study notes that rasburicase can generate high concentrations of hydrogen peroxide, which could potentially cause hemolysis and methemoglobin formation in patients with certain enzyme deficiencies 6.
Potential Risks and Considerations
- The use of rasburicase may be associated with certain risks, such as hemolysis and methemoglobin formation, particularly in patients with glucose-6-phosphate dehydrogenase deficiency 6.
- The generation of hydrogen peroxide by rasburicase may also interfere with certain laboratory assays, including those used to measure serum uric acid concentration 6.
- Further research is needed to fully understand the potential effects of uricase therapy on kidney stones and to determine the safety and efficacy of rasburicase in this context.