Preventing heme-induced nephropathy in children with glucose 6 phosphate dehydrogenase deficiency: is there a role for acetazolamide?

We read with great interest the article by Safaei-Asl et al. [1]. Many thanks to the authors for their contributions to the study of the fluid therapy method for preventing heme-induced nephropathy in children with glucose 6 phosphate dehydrogenase (G6PD) deficiency. We would like to point out some concerns which we think will contribute to the validity of this research.

Regarding the acetazolamide used in the control group in the article, we think there are some issues that need to be considered and stated separately. First, although acetazolamide at a dose of up to 1 g/d is recognized as safe, the inclusion criteria include children aged 3 months to 18 years, a wide age range, and there is no data to support the safety of acetazolamide in younger children such as those under 2 years of age. Second, it is well-documented that acetazolamide causes a decrease in blood potassium and that this occurs throughout the course of administration [2]. In the results, there is no significant difference in serum potassium among the three groups within 12, 48, and 72 h. Is there a problem? Third, a retrospective study showed that acute kidney injury occurred in 26.8% (n = 233) of 868 ICU patients less than 19 years of age between 48 h prior to intravenous acetazolamide treatment and 72 h after termination of acetazolamide treatment [3]. Although the probability of acute kidney injury with oral acetazolamide may be smaller than this data, the therapeutic efficacy of acetazolamide in preventing heme-induced nephropathy in children with glucose 6 phosphate dehydrogenase deficiency is questionable.

G6PD deficiency is associated with varying degrees of insidious kidney injury during acute haemolytic episodes. In G6PD deficiency, massive intravascular haemolysis leads to acute kidney failure, while acute tubular necrosis may complicate severe haemolytic episodes. Kidney injury may persist after the acute haemolytic episode has subsided. We agree with the authors that these patients need to be followed up and evaluated for kidney function over a longer period of time.

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