BACKGROUND Sodium-glucose cotransporter-2 inhibitors (SGLT2i) lower the risk of kidney failure in persons with type 2 diabetes. The presumed mechanism of action is through greater delivery of sodium to the distal tubule, activation of tubuloglomerular feedback which lowers glomerular filtration rate (GFR) and intra-glomerular pressure. SGLT2is are not approved for use in persons with type 1 diabetes due to the risk of diabetic ketoacidosis. Acetazolamide, a proximal tubule diuretic, delivers more sodium to the distal nephron, and may activate tubuloglomerular feedback in a similar way to SGLT2is without a higher risk of diabetic ketoacidosis. The kidney effects and safety of acetazolamide in persons with type 1 diabetes have not been well studied. METHODS We conducted a dose-escalation trial to determine the effects of 3 dosages of oral acetazolamide (62.5mg, 125mg, and 250mg, all twice-daily) in 12 persons with type 1 diabetes. Participants were treated for 2 weeks followed by a 2-week washout before exposure to the next dosage level. Blood and urine chemistries, as well as iohexol measured GFR, were assessed before and after each treatment interval. We aimed to identify a dose that maximized measured GFR reductions while minimizing adverse effects. RESULTS The mean age was 46±17 years, 100% were White, and 75% were female. The mean measured GFR was 89±18ml/min/1.73m2 at baseline. Acetazolamide reduced measured GFR by 15% (95% CI 9, 21), 14% (95% CI 7, 21), and 15% (95% CI 10, 21) after 2 weeks at the 62.5mg, 125mg, and 250mg twice-daily dosage levels respectively. The measured GFR reduction was fully reversed after each 2-week washout. Serum bicarbonate was reduced by 2.3, 4.2 and 4.4 mEq/L with escalating doses, and no episodes of hypokalemia (< 3.5 mEq/L) were observed. CONCLUSIONS Among persons with type 1 diabetes and preserved kidney function, acetazolamide caused an acute, reversible reduction in measured GFR without effects on glucose metabolism.

中文翻译：

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乙酰唑胺治疗和 1 型非白蛋白尿糖尿病患者的肾功能。


背景钠-葡萄糖协同转运蛋白 2 抑制剂 （SGLT2i） 可降低 2 型糖尿病患者发生肾衰竭的风险。推测的作用机制是通过更多地将钠输送到远端肾小管，激活肾小球反馈，从而降低肾小球滤过率 （GFR） 和肾小球内压。由于存在糖尿病酮症酸中毒的风险，SGLT2is 未被批准用于 1 型糖尿病患者。乙酰唑胺是一种近端肾小管利尿剂，可向远端肾单位输送更多的钠，并可能以类似于 SGLT2is 的方式激活肾小球反馈，而不会增加糖尿病酮症酸中毒的风险。乙酰唑胺对 1 型糖尿病患者的肾脏影响和安全性尚未得到充分研究。方法 我们进行了一项剂量递增试验，以确定 3 剂口服乙酰唑胺 （62.5mg、125mg 和 250mg，均每日两次） 对 12 名 1 型糖尿病患者的影响。参与者接受了 2 周的治疗，然后进行了 2 周的清除，然后暴露于下一个剂量水平。在每个治疗间隔之前和之后评估血液和尿液化学以及碘海醇测量的 GFR。我们旨在确定一种剂量，该剂量可以最大限度地提高测量的 GFR 降低，同时最大限度地减少不良反应。结果 平均年龄为 46±17 岁，100% 为白人，75% 为女性。基线时测得的平均 GFR 为 89±18ml/min/1.73m2。乙酰唑胺在 62.5 毫克、 125 毫克和 250 毫克每日两次剂量水平下，2 周后测量的 GFR 降低了 15% （95% CI 9， 21） 、 14% （95% CI 7， 21） 和 15% （95% CI 10， 21）。每次 2 周清除后，测得的 GFR 降低完全逆转。随着剂量的增加，血清碳酸氢盐降低 2.3、4.2 和 4.4 mEq/L，并且没有低钾血症发作 （< 3.5 mmol/L （5 mmol/L） 的测定。结论 在 1 型糖尿病患者和肾功能保留的患者中，乙酰唑胺导致测得的 GFR 急性、可逆性降低，而对葡萄糖代谢没有影响。