钠-葡萄糖协同转运蛋白2抑制剂在伴或不伴晚期慢性肾脏病患者中的疗效与安全性：系统评价和Meta分析
Efficacy and Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Patients with and without Advanced CKD: Systematic Review and Meta-Analysis.
作者信息
Elenjickal Elias John, Travlos Christoforos K, Luu Judy, Lemay Serge, Suri Rita S, Mavrakanas Thomas A
机构信息
Division of Nephrology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
出版信息
Clin J Am Soc Nephrol. 2025 Mar 26;20(6):788-809. doi: 10.2215/CJN.0000000693.
KEY POINTS
Treatment with sodium-glucose cotransporter-2 inhibitor (SGLT-2i) provides kidney and cardiovascular protection in patients with advanced CKD. The glycosuric action of SGLT-2i is attenuated in advanced CKD resulting in no change in glycated hemoglobin and fewer volume depletion events. The use of SGLT-2i did not increase the incidence of AKI, urine infections, fractures, or treatment discontinuation due to adverse events.
BACKGROUND
The efficacy and safety of sodium-glucose cotransporter-2 inhibitor (SGLT-2i) in patients with advanced CKD, defined as an eGFR <30 ml/min per 1.73 m, has not been adequately studied.
METHODS
We conducted a systematic review and meta-analysis of phase 3 randomized controlled trials of SGLT-2i in adults. We searched the medical literature analysis and retrieval system online and excerpta medica database databases from inception to April 2024. The primary outcomes were composite kidney (worsening kidney function, kidney failure, and kidney or cardiovascular [CV] death) and CV (CV death or hospitalization for heart failure) outcomes. Secondary outcomes included other reported CV and kidney outcomes, eGFR slopes, mechanistic, and safety outcomes. The risk ratios (RR) were estimated using a random effects model. Interaction effects were estimated for treatment effect modification by baseline eGFR (<30 and ≥30 ml/min per 1.73 m).
RESULTS
A total of ten randomized controlled trials were included (total of 4800 patients with eGFR <30 ml/min per 1.73 m). Participants were randomized to receive either placebo or an SGLT-2i. The use of SGLT-2i was associated with a lower incidence of the primary composite kidney outcome in patients with eGFR <30 ml/min per 1.73 m (RR, 0.79; 95% confidence interval [CI], 0.70 to 0.89) and ≥30 ml/min per 1.73 m (RR, 0.71; 95% CI, 0.64 to 0.79). The incidence of the primary CV outcome was numerically lower in the SGLT-2i arm in patients with eGFR <30 ml/min per 1.73 m (RR, 0.88; 95% CI, 0.71 to 1.10). In patients with eGFR ≥30 ml/min per 1.73 m, SGLT-2i use was associated with a lower incidence of the composite CV outcome (RR, 0.77; 95% CI, 0.71 to 0.83). However, there was no interaction between advanced CKD status and the effect of SGLT-2i on any of the primary or secondary outcomes. The incidence of adverse events was similar in both arms.
CONCLUSIONS
SGLT-2i retain their kidney and CV protective effect in patients with advanced CKD, with no added safety concerns.
关键点
使用钠-葡萄糖协同转运蛋白2抑制剂（SGLT-2i）可对晚期慢性肾脏病（CKD）患者起到肾脏和心血管保护作用。在晚期CKD中，SGLT-2i的糖尿作用减弱，糖化血红蛋白无变化，容量耗竭事件减少。使用SGLT-2i不会增加急性肾损伤（AKI）、泌尿系统感染、骨折或因不良事件导致治疗中断的发生率。
背景
钠-葡萄糖协同转运蛋白2抑制剂（SGLT-2i）在估算肾小球滤过率（eGFR）<30 ml/（min·1.73 m²）的晚期CKD患者中的疗效和安全性尚未得到充分研究。
方法
我们对SGLT-2i在成人中的3期随机对照试验进行了系统评价和荟萃分析。我们检索了从创建到2024年4月的医学文献分析和检索系统在线数据库以及医学文摘数据库。主要结局为复合肾脏结局（肾功能恶化、肾衰竭以及肾脏或心血管[CV]死亡）和CV结局（CV死亡或因心力衰竭住院）。次要结局包括其他报告的CV和肾脏结局、eGFR斜率、机制和安全性结局。风险比（RR）采用随机效应模型估算。通过基线eGFR（<30和≥30 ml/（min·1.73 m²））对治疗效果修正的交互作用进行了估算。
结果
共纳入10项随机对照试验（共4800例eGFR<30 ml/（min·1.73 m²）的患者）。参与者被随机分配接受安慰剂或SGLT-2i。在eGFR<30 ml/（min·1.73 m²）的患者中，使用SGLT-2i与较低的主要复合肾脏结局发生率相关（RR，0.79；95%置信区间[CI]，0.70至0.89），在eGFR≥30 ml/（min·1.73 m²）的患者中也是如此（RR，0.71；95%CI，0.64至0.79）。在eGFR<30 ml/（min·1.73 m²）的患者中，SGLT-2i组的主要CV结局发生率在数值上较低（RR，0.88；95%CI，0.71至1.10）。在eGFR≥30 ml/（min·1.73 m²）的患者中，使用SGLT-2i与较低的复合CV结局发生率相关（RR，0.77；95%CI，0.71至0.83）。然而，晚期CKD状态与SGLT-2i对任何主要或次要结局的影响之间没有交互作用。两组不良事件的发生率相似。
结论
SGLT-2i在晚期CKD患者中仍具有肾脏和CV保护作用，且无额外的安全问题。
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