Kidney Week

Abstract: SA-PO323

Acetazolamide Therapy and Kidney Function in Persons with Type 1 Diabetes: The ATAK-DM1 Trial

Session Information

• Diabetic Kidney Disease: Clinical Pathology, Diagnostic and Treatment Advances
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Ginsberg, Charles, University of California San Diego, La Jolla, California, United States

Charles Ginsberg, MD, MA

• Seegmiller, Jesse C., University of Minnesota Medical School, Minneapolis, Minnesota, United States

Jesse C. Seegmiller, PhD

• Vallon, Volker, University of California San Diego, La Jolla, California, United States

Volker Vallon, MD, FASN

• Thomas, Robert L., University of California San Diego, La Jolla, California, United States

Robert L. Thomas, MD, PhD

• Ix, Joachim H., University of California San Diego, La Jolla, California, United States

Joachim H. Ix, MD, FASN

Background

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) lower risk of kidney failure through greater sodium delivery to the distal tubule and activation of tubuloglomerular feedback (TGF) thereby lowering glomerular pressure which lowers glomerular filtration rate (GFR). SGLT2i are not widely used in type 1 diabetes mellitus (T1DM) due to diabetic ketoacidosis (DKA) risk. Acetazolamide, a proximal tubule diuretic, delivers sodium to the distal nephron, and may activate TGF without glycemic effects. The kidney response and safety of acetazolamide in T1DM patients are not well known.

Methods

We conducted a dose escalation trial to study the effects of three doses of oral acetazolamide (62.5, 125, and 250mg, all twice daily) in 12 persons with T1DM and eGFR> 45ml/min/1.73m². Participants were treated for 2 weeks followed by a 2 week wash out before the next dose level. Blood chemistries were measured before and after each treatment interval. GFR was measured (mGFR) using iohexol. We hypothesized that acetazolamide would safely cause reversible reductions in GFR indicating stimulation of TGF.

Results

The 12 participants had mean age 46±17 years, all participants were White, and 9 were female. The mean mGFR was 89±18ml/min/1.73m² at baseline. Acetazolamide caused a 14.7(95%CI 8.5,21.0)%, 13.8(6.5,21.0)%, and 15.4(9.9,21.0)%, reduction in mGFR over 2 weeks on the 62.5, 125, and 250mg doses, respectively (Figure). These changes were not attenuated when accounting for body weight changes. GFR returned to baseline after a 2 week washout for each dose. Serum bicarbonate was reduced by 2.3(1.2,3.3), 4.1(3.3,4.8) and 4.4(2.3,6.5)mEq/L with the three escalating doses, respectively. There were no episodes of hypokalemia (serum potassium< 3.5 mEq/L) observed for any dose.

Conclusion

Among persons with T1DM, acetazolamide caused an acute reversible reduction in GFR with moderate concurrent reductions in serum bicarbonate.

Funding

• NIDDK Support