Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark,
Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Nephron. 2024;148(3):137-142. doi: 10.1159/000534396. Epub 2023 Oct 9.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors exert a kidney protective effect in patients with diabetic kidney disease. Several mechanisms have been proposed, but why precisely SGLT2 inhibition has a kidney protective effect is incompletely understood. Clinical trials using SGLT2 inhibitors have found them to induce a rapid weight loss likely due to loss of sodium and subsequently fluid. While SGLT2 inhibitors are reported to increase hematocrit, it remains unknown whether the natriuretic and aquaretic effect reduces patient's blood volume and whether this could partly explain its kidney protective effects. A blood volume reduction could induce several beneficial effects with reduction in arterial and venous blood pressure as two central mechanisms. The aim of this paper was to review current techniques for assessing patient blood volume that could enhance our understanding of SGLT2 inhibitors' physiological effects.
Changes induced by SGLT2 inhibitors on erythrocyte volume and plasma volume can be assessed by tracer dilution techniques that include radioisotopes, indocyanine green (ICG) dye, or carbon monoxide (CO). Techniques with radioisotopes can provide direct estimates of both erythrocyte volume and plasma volume but are cumbersome procedures and the radiation exposure is a limitation for repeated measures in clinical studies. Methods more suitable for repeated assessment of erythrocyte and plasma volume include dilution of injected ICG dye or dilution of inhaled CO. ICG dye requires higher precision with timed blood samples and provides only a direct estimate of plasma volume wherefrom erythrocyte volume is estimated. Inhalation of CO is a time-effective and automated method that provides measure of the total hemoglobin mass wherefrom erythrocyte and plasma volumes are estimated.
A kidney protective effect has been observed in clinical trials with SGLT2 inhibitors, but the underlying mechanisms are not fully understood. Significant weight loss within weeks has been reported in the SGLT2 inhibitor trials and could be related to a reduction in blood volume secondary to increased natriuresis and aquaresis. Alterations in blood volume compartments can be quantified by tracer dilution techniques and further improve our understanding of kidney protection from SGLT2 inhibitors.
钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂在糖尿病肾病患者中具有肾脏保护作用。已经提出了几种机制，但为什么 SGLT2 抑制具有肾脏保护作用尚不完全清楚。使用 SGLT2 抑制剂的临床试验发现，它们会导致体重迅速下降，可能是由于钠和随后的液体丢失所致。虽然 SGLT2 抑制剂被报道会增加血细胞比容，但尚不清楚利钠和利尿作用是否会减少患者的血容量，以及这是否可以部分解释其肾脏保护作用。血容量减少可能会通过降低动脉和静脉血压这两个中心机制引起多种有益作用。本文的目的是综述评估患者血容量的当前技术，以增强我们对 SGLT2 抑制剂生理作用的理解。
SGLT2 抑制剂对红细胞体积和血浆体积的影响可以通过示踪剂稀释技术来评估，包括放射性同位素、吲哚菁绿（ICG）染料或一氧化碳（CO）。放射性同位素技术可以直接估计红细胞体积和血浆体积，但操作繁琐，放射性暴露是临床研究中重复测量的限制。更适合重复评估红细胞和血浆体积的方法包括注射 ICG 染料的稀释或吸入 CO 的稀释。ICG 染料需要更精确的时间采血样本，并且仅直接估计血浆体积，从中可以估计红细胞体积。吸入 CO 是一种有效且自动化的方法，可测量总血红蛋白质量，从中可以估计红细胞和血浆体积。
在 SGLT2 抑制剂的临床试验中观察到了肾脏保护作用，但潜在机制尚不完全清楚。在 SGLT2 抑制剂试验中报告了数周内体重显著减轻，这可能与增加的利钠和利尿作用导致的血容量减少有关。通过示踪剂稀释技术可以定量评估血容量容积变化，并进一步提高我们对 SGLT2 抑制剂的肾脏保护作用的理解。
