Copur Sidar, Yildiz Abdullah, Basile Carlo, Tuttle Katherine R, Kanbay Mehmet
Department of Medicine, Koc University School of Medicine, Istanbul, Turkey.
Associazione Nefrologica Gabriella Sebastio, Martina Franca, Italy.
J Nephrol. 2023 Jan;36(1):31-43. doi: 10.1007/s40620-022-01422-w. Epub 2022 Aug 13.
A novel class of oral glucose lowering drugs, sodium-glucose co-transporter type 2 inhibitors (SGLT2is), has shown additional beneficial effects on body weight, serum uric acid levels, blood pressure, and cardiac and renal function. Conflicting data have been published regarding the potential risk of acute kidney injury (AKI) when using SGLT2is. Aim of this manuscript was to review the current literature on this issue. SGLT2is induce a mild acute decline in estimated glomerular filtration rate, attributed to the effect of proximal tubular natriuresis on tubuloglomerular feedback through increased macula densa sodium delivery, leading to afferent arteriole vasoconstriction and reduced intraglomerular pressure. This functional effect with a subsequent rise in serum creatinine fulfills the creatinine-based criteria for AKI, as defined in clinical practice and trial settings. Other proposed potential mechanisms as to how SGLT2is lead to AKI include osmotic diuresis leading to volume depletion, increased urinary uric acid levels, intratubular oxidative stress, local inflammation and tubular injury. Despite the warning published by the US Food and Drug Administration in 2016 about a potential risk of AKI and the report of some clinical cases of AKI after treatment with SGLT2is, large observational real-life retrospective studies, randomized controlled trials and propensity-matched analyses of data from clinical practice unambiguously demonstrate that SGLT2is are safe for the kidney and do not predispose to AKI. In conclusion, while we can probably stop worrying about AKI risk when using SGLT2is, the question whether these agents should be withheld in the presence of clinical situations at high risk for AKI remains unaddressed.
一类新型的口服降糖药物，即钠-葡萄糖协同转运蛋白2抑制剂（SGLT2is），已显示出对体重、血清尿酸水平、血压以及心脏和肾脏功能具有额外的有益作用。关于使用SGLT2is时急性肾损伤（AKI）的潜在风险，已发表了相互矛盾的数据。本文的目的是综述关于这个问题的当前文献。SGLT2is会导致估计肾小球滤过率出现轻度急性下降，这归因于近端肾小管利钠作用通过增加致密斑钠输送对管球反馈的影响，导致入球小动脉血管收缩和肾小球内压力降低。这种功能效应以及随后血清肌酐升高符合临床实践和试验环境中定义的基于肌酐的AKI标准。关于SGLT2is如何导致AKI的其他提出的潜在机制包括渗透性利尿导致容量耗竭、尿尿酸水平升高、肾小管内氧化应激、局部炎症和肾小管损伤。尽管美国食品药品监督管理局在2016年发布了关于AKI潜在风险的警告，并且有一些关于使用SGLT2is治疗后发生AKI临床病例的报告，但大型观察性现实生活回顾性研究、随机对照试验以及对临床实践数据的倾向匹配分析明确表明，SGLT2is对肾脏是安全的，不会诱发AKI。总之，虽然我们在使用SGLT2is时可能可以不再担心AKI风险，但在存在AKI高风险临床情况时是否应停用这些药物的问题仍未得到解决。
