Acetazolamide-induced metabolic acidosis in pediatric idiopathic intracranial hypertension: associations with bone mineral density, growth, and kidney function.

BACKGROUND

Although acetazolamide is the main medical treatment for idiopathic intracranial hypertension (IIH), data on acetazolamide-induced metabolic acidosis and its long-term outcomes are limited. This study aimed to investigate the severity of acetazolamide-related metabolic acidosis, associated risk factors, and its effects on bone mineral density (BMD), growth, and kidney function.

METHODS

This retrospective cohort study included pediatric patients with IIH treated with acetazolamide between 2018 and 2025. Demographic and clinical characteristics, anthropometric and laboratory findings at diagnosis and during follow-up, BMD measurements, and ultrasonography findings were collected. Metabolic acidosis was categorized by severity. Minimum and mean serum bicarbonate levels during follow-up were recorded.

RESULTS

Forty-one patients (65.9% female; mean age 11.2 ± 3.1 years) were included. Metabolic acidosis was observed in all patients (39.0% mild, 53.7% moderate, 7.3% severe). Patients with moderate-to-severe acidosis had significantly lower BMI Z-scores and younger ages at diagnosis compared with those with mild acidosis. In multivariable analysis, cumulative acetazolamide dose remained independently associated with moderate/severe metabolic acidosis (OR 1.30, 95% CI 1.00-1.69; p = 0.049). BMD was assessed in 35 patients after a median acetazolamide exposure of 14 months and mildly reduced/low BMD was detected in 22.9%. Higher cumulative acetazolamide exposure and lower minimum bicarbonate levels were associated with mildly reduced/low BMD in univariable analyses; however, these associations did not remain significant after multivariable adjustment. Although estimated glomerular filtration rate declined modestly from baseline to the last visit, this change was not associated with acidosis severity, treatment duration, or cumulative acetazolamide dose.

CONCLUSIONS

Metabolic acidosis is highly prevalent among children receiving acetazolamide for IIH, and greater cumulative acetazolamide exposure appears to be associated with more severe acidosis. Lower bicarbonate levels and higher cumulative acetazolamide exposure were associated with mildly reduced/low BMD in univariable analyses; however, these associations did not remain significant after multivariable adjustment. The limited number of patients undergoing BMD assessment, the relatively short exposure duration in some patients, and the absence of baseline BMD measurements limit definitive conclusions regarding the skeletal effects of acetazolamide.