Acetazolamide may reduce GFR without impacting glucose metabolism in type 1 diabetes
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Key takeaways:
- Acetazolamide was associated with reduced measured GFR by 14% to 15% at three different doses.
- Serum bicarbonate levels also decreased with escalating doses.
Acetazolamide was associated with an acute, reversible drop in GFR without impacting glucose metabolism for adults with type 1 diabetes and preserved kidney function, according to study data.
“Therapies that stimulate tubuloglomerular feedback without the risks of ketoacidosis are needed to allow patients with type 1 diabetes to realize the kidney benefits of this mechanism of action,” Charles Ginsberg, MD, assistant professor of medicine in the division of nephrology-hypertension at the University of California, San Diego, and colleagues wrote in the Journal of the American Society of Nephrology. “Acetazolamide is a carbonic anhydrase inhibitor that may fit these criteria. By inhibiting carbonic anhydrase, acetazolamide acts as a mild diuretic that blocks sodium reabsorption in the proximal tubule. This effect acts similar to SGLT2 inhibitors to increase sodium delivery to distal regions of the kidney tubule.”
As part of the trial, researchers studied 12 patients with a mean age of 46 years and type 1 diabetes. They tested 62.5 mg, 125 mg and 250 mg doses of oral acetazolamide given twice a day. Treatment lasted for 2 weeks, with a 2-week washout between each dosage level.
All participants were white, most were women and baseline GFR was 89 mL/min/1.73 m2.
Enrollment began in 2022 and ended in 2024.
Investigators tested blood and urine chemistries and iohexol-measured GFR before and after each interval. The study aimed to find the effects of acetazolamide on GFR and identify a dose that maximized reductions in GFR levels while also reducing adverse effects. Acetazolamide reduced measured GFR by 14% to 15% at all doses, according to the researchers, with reductions fully reversed after each 2-week washout period. In addition, serum bicarbonate levels decreased with escalating doses without episodes of hypokalemia.
“Further studies are urgently needed to evaluate if the early intervention of GFR reduction with acetazolamide translates to long-term kidney preservation,” the researchers wrote. “Additionally, studies evaluating changes in renal blood flow in response to acetazolamide may be informative as to mechanisms of potential kidney protection with acetazolamide. Finally, larger and longer trials are needed to further characterize the safety profile and adherence rates of low dose oral acetazolamide in persons with type 1 diabetes.”
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