Acetazolamide-Induced Nephrolithiasis in Idiopathic Intracranial Hypertension Patients

Idiopathic intracranial hypertension (IIH) is a neurological disorder characterized by elevated intracranial pressure of unknown cause. Acetazolamide is widely used as the initial treatment option; however, previously published evidence suggests that this drug may also increase the risk of nephrolithiasis. The purpose of this study was to examine daily acetazolamide use and its relationship to nephrolithiasis and compare clinical presentation of IIH between those with and without nephrolithiasis.

We conducted a case-control study using patient data collected by the Intracranial Hypertension Registry. A total of 670 patients were identified as potential study participants, 19 meeting the case definition of developing a stone during acetazolamide treatment for IIH. From the remaining pool of eligible participants, 40 controls were randomly selected. Two-sampled t tests, Fisher exact testing, and exact logistic regression were used to examine differences between cases and controls and to ascertain associations with IIH clinical features and mean daily acetazolamide dosage.

Among all eligible patients, 19 (2.8%) developed a stone during acetazolamide treatment for IIH. Among these patients, 17 (89.5%) developed a stone within 1.5 years of initial acetazolamide treatment. Daily acetazolamide use was not significantly related to stone development (odds ratio = 0.95; 95% confidence intervals: 0.86-1.05). Additionally, the relationship between the clinical presentation of IIH at the time of diagnosis (signs and symptoms) and stone development did not reach statistical significance (P > 0.05).

Our results demonstrate that: 1) stone formation during acetazolamide treatment is a relatively infrequent occurrence within the IIH population; 2) among patients who develop a stone, formation is likely to occur within the first year and half; 3) there is no evidence to support the association between acetazolamide daily dosage and stone development; and 4) no unique IIH disease features at the time of diagnosis are associated with stone development. Treatment with acetazolamide should be administered to IIH patients with caution and closely monitored for stone development especially within the first year and a half of treatment.