Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, La Jolla, CA, USA; Department of Pharmacology, University of California San Diego, La Jolla, CA, USA; VA San Diego Healthcare System, 3350 La Jolla Village Drive (9151), San Diego, CA 92161, USA.
Heart Fail Clin. 2022 Oct;18(4):539-549. doi: 10.1016/j.hfc.2022.03.005.
SGLT2 inhibitors can protect the kidneys of patients with and without type 2 diabetes from failing. This includes blood glucose dependent and independent mechanisms. SGLT2 inhibitors lower glomerular pressure and filtration, thereby reducing the physical stress on the filtration barrier and the oxygen demand for tubular reabsorption. This improves cortical oxygenation, which, together with lesser tubular glucotoxicity and improved mitochondrial function and autophagy, can reduce proinflammatory and profibrotic signaling and preserve tubular function and GFR in long term. By shifting transport downstream, SGLT2 inhibitors may mimic systemic hypoxia and stimulate erythropoiesis, which improves oxygen delivery to the kidney and other organs.
SGLT2 抑制剂可保护有或无 2 型糖尿病的患者的肾脏免于衰竭。这包括血糖依赖和非依赖机制。SGLT2 抑制剂降低肾小球压力和滤过,从而减轻滤过屏障的物理压力和管状重吸收的氧气需求。这改善了皮质氧合,再加上较少的管状糖毒性、改善的线粒体功能和自噬,可以减少促炎和促纤维化信号,长期保存管状功能和肾小球滤过率。通过将转运物向下游转移,SGLT2 抑制剂可以模拟全身缺氧并刺激红细胞生成,从而改善肾脏和其他器官的氧气输送。