A recent study published in Journal of Neuro-Ophthalmology explores the heightened risk of kidney stones in IIH patients treated with CAIs. The retrospective analysis of over 44,000 patients revealed a consistent increase in kidney stone formation, especially in male patients. This finding underscores the need for clinicians to adopt tailored treatment approaches, particularly for those with a history of kidney stones or at higher risk. Click image to enlarge.

One of the main treatment strategies for patients with idiopathic intracranial hypertension (IIH), a condition that can include chronic debilitating headaches, irreversible visual impairments and blindness in extreme cases, is the use of carbonic anhydrase inhibitors (CAIs), typically acetazolamide (Diamox). Although this medication is effective for improving visual outcomes, it’s been shown to cause kidney stone development in patients. In an effort to explore shortcomings in risk mitigation strategies, a group of researchers conducted a study—newly published in Journal of Neuro-Ophthalmology—that demonstrates the significantly elevated risk for kidney stones in patients who were treated with CAIs.

The retrospective cohort analysis was performed using a global database and consisted of a study group of patients treated with either acetazolamide or methazolamide and a control cohort that didn’t receive any treatment. After propensity score matching, each group included 22,464 patients with a mean age of 31.4 years in the CAI group and 31.3 years for the control group. IIH is more common in women, which was reflected in the study population, comprised of 84.3% female and. 13.8% male subjects in the study group and nearly identical proportions in the control group. 

At one-year, the treated group had a 0.35% higher risk of developing kidney stones than the untreated group with a risk ratio (RR) of 1.49. According to the paper on the study, this elevated risk continued at the one- and two-year mark, where the risk difference was 0.29% and the RR increased to 2.24. By years two and three, there was a decrease in risk of 0.11% and RR of 1.51. The study authors noted that, although they observed a consistent decrease in risk difference over time, the risk for kidney stones remained persistently elevated in patients who were treated with at least 500mg of acetazolamide. 

As they delved deeper into the subgroups, researchers found the risk was more pronounced in male patients. “This may be explained by the fact that, although IIH is less common in men, they tend to exhibit greater disease severity, are more likely to develop vision loss, and often require more aggressive treatment,” they wrote in their paper. Also in line with previous research was their observed decrease in risk among Black patients. 

It’s been demonstrated that patients on Diamox experience decreased excretion of citrate, which is related to the formation of calcium stones. “Understanding these biochemical pathways provides critical context for developing strategies to mitigate this risk, potentially through dietary modifications (e.g., oxalate restriction) or adjunctive therapies that could help maintain citrate levels and prevent stone formation,” wrote the authors in their paper. Future studies should “explore the mechanisms underlying the increased risk of kidney stones, and explore risk factors in greater detail including genetic predisposition, diet and the use of supplements,” they continued.

The authors say the large sample size and global data set were among the study’s strengths; however, the retrospective nature of the analysis includes inherent limitations, such as potential residual confounding (i.e., unaccounted for influences) and the reliance on accurate diagnostic coding for case identification.

In conclusion, the authors believe this information could be crucial for clinicians prescribing CAIs, particularly in those with a history of kidney stones, and “necessitates a more tailored approach to treatment,” they wrote.