From the FDA Drug Label
Kidney Stones A total of 32/2,086 (1. 5%) of adults exposed to topiramate during its adjunctive epilepsy therapy development reported the occurrence of kidney stones, an incidence about 2 to 4 times greater than expected in a similar, untreated population. ... Carbonic anhydrase inhibitors,e. g., acetazolamide or dichlorphenamide, promote stone formation by reducing urinary citrate excretion and by increasing urinary pH.
The 24-hour urine collection will most likely demonstrate hypocitraturia because topiramate is a carbonic anhydrase inhibitor, which reduces urinary citrate excretion and increases urinary pH, thereby promoting stone formation 1.
From the Research
A 24-hour urine collection in a 38-year-old woman with kidney stones who is taking topiramate for migraines will most likely demonstrate hypocitraturia (decreased citrate excretion). This is because topiramate is a carbonic anhydrase inhibitor that causes metabolic acidosis, which paradoxically leads to alkaline urine, and also reduces urinary citrate levels, a natural inhibitor of calcium stone formation. The combination of these effects creates an environment favorable for kidney stone formation, particularly calcium phosphate stones which form more readily in alkaline urine. According to the most recent study 2, topiramate use leads to hypocitraturia and elevated pH, resulting in a higher rate of calcium phosphate stone formation compared to the general population. Additionally, stopping topiramate leads to a significant increase in citrate excretion and normalization of pH, indicating that these metabolic disturbances are reversible with medication cessation. Other studies, such as 3, 4, and 5, also support the finding that topiramate reduces urinary citrate levels, but the most recent study 2 provides the strongest evidence for the effects of topiramate on urinary metabolic disturbances. Patients taking topiramate should be advised to maintain adequate hydration and may benefit from citrate supplementation if hypocitraturia is confirmed. Some key points to consider include:
- Topiramate induces hypocitraturia, which is a significant risk factor for kidney stone formation
- The medication causes metabolic acidosis, leading to alkaline urine, which favors the formation of calcium phosphate stones
- Citrate supplementation may be beneficial for patients taking topiramate to reduce the risk of kidney stone formation
- Stopping topiramate can lead to a significant increase in citrate excretion and normalization of pH, indicating that the metabolic disturbances caused by the medication are reversible.