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Effects of SGLT2 Inhibitors on Kidney and Cardiovascular Function
Annual Review of Physiology ( IF 15.7 ) Pub Date : 2021-02-10 , DOI: 10.1146/annurev-physiol-031620-095920
Volker Vallon 1, 2, 3 , Subodh Verma 4, 5
Affiliation  

SGLT2 inhibitors are antihyperglycemic drugs that protect kidneys and the heart of patients with or without type 2 diabetes and preserved or reduced kidney function from failing. The involved protective mechanisms include blood glucose–dependent and –independent mechanisms: SGLT2 inhibitors prevent both hyper- and hypoglycemia, with expectedly little net effect on HbA1C. Metabolic adaptations to induced urinary glucose loss include reduced fat mass and more ketone bodies as additional fuel. SGLT2 inhibitors lower glomerular capillary hypertension and hyperfiltration, thereby reducing the physical stress on the filtration barrier, albuminuria, and the oxygen demand for tubular reabsorption. This improves cortical oxygenation, which, together with lesser tubular gluco-toxicity, may preserve tubular function and glomerular filtration rate in the long term. SGLT2 inhibitors may mimic systemic hypoxia and stimulate erythropoiesis, which improves organ oxygen delivery. SGLT2 inhibitors are proximal tubule and osmotic diuretics that reduce volume retention and blood pressure and preserve heart function, potentially in part by overcoming the resistance to diuretics and atrial-natriuretic-peptide and inhibiting Na-H exchangers and sympathetic tone.

中文翻译:


SGLT2 抑制剂对肾脏和心血管功能的影响

SGLT2 抑制剂是一种降血糖药物,可保护患有或未患有 2 型糖尿病的患者的肾脏和心脏,并保留或降低肾功能,使其免于衰竭。所涉及的保护机制包括血糖依赖性和非血糖依赖性机制:SGLT2 抑制剂可预防高血糖和低血糖,预计对 HbA1C 的净影响很小。对诱导尿糖损失的代谢适应包括减少脂肪量和更多酮体作为额外燃料。SGLT2抑制剂可降低肾小球毛细血管高压和过度滤过,从而减少滤过屏障的物理压力、白蛋白尿和肾小管重吸收的需氧量。这改善了皮质氧合,再加上较小的肾小管葡萄糖毒性,可以长期保持肾小管功能和肾小球滤过率。SGLT2 抑制剂可以模拟全身缺氧并刺激红细胞生成,从而改善器官的氧输送。SGLT2 抑制剂是近端小管和渗透性利尿剂,可降低容量潴留和血压并保护心脏功能,部分原因可能是克服利尿剂和心房钠尿肽的耐药性并抑制 Na-H 交换剂和交感神经张力。

更新日期:2021-02-11
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