Shiau Chu-Hsuan, Tsau Li-Yun, Kao Chih-Chin, Peng Yu-Ching, Bai Chyi-Huey, Wu Jeng-Cheng, Hou Wen-Hsuan
Department of Education, Taipei Medical University Hospital, Taipei, Taiwan.
Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan.
Int Urol Nephrol. 2024 Apr;56(4):1359-1381. doi: 10.1007/s11255-023-03789-6. Epub 2023 Sep 26.
Owing to the pharmacological mechanism, sodium-glucose cotransporter 2 inhibitors (SGLT2is) may be less effective in patients with reduced renal functions, but no systematic review or meta-analysis addressed chronic kidney disease (CKD) patients specifically. We aimed to assess the efficacy and safety of SGLT2is in CKD patients.
We conducted a systematic review and meta-analysis of randomized controlled trials. Mean difference (MD) were pooled for the decline of glomerular filtration rate (eGFR) and change in urine albumin-to-creatinine ratio (uACR). Hazard ratio (HR) and rate ratio (RR) were pooled for composite of renal outcomes and adverse effects.
Thirty articles were identified. Overall MD in rate of eGFR decline was 0.02 (P = 0.05), with a borderline significant difference favoring SGLT2is, while the change in uACR from baseline was - 141.34 mg/g and hazard ratio of composite renal outcomes was 0.64 significantly favoring SGLT2is. Subgroup analyses showed that the long-term renal function, participants with baseline macroalbuminuria, and stage 4 CKD patients had significantly slower eGFR decline rate in SGLT2is compared to the placebo group. Risks of genital mycotic infection and ketoacidosis were significantly higher among the SGLT2is group than placebo.
For CKD patients, no matter diabetic or non-diabetic, our study showed potential renoprotective effects favoring SGLT2is in overall and long-term phase, and in patients with macroalbuminuria or stage 4 CKD. However, only slight increased risk of adverse effects among the SGLT2is group is observed. Therefore, we concluded that in CKD patients, prescribing SGLT2is was safe and had renal benefits.
由于药理机制，钠-葡萄糖协同转运蛋白2抑制剂（SGLT2is）在肾功能减退的患者中可能疗效较差，但尚无系统评价或荟萃分析专门针对慢性肾脏病（CKD）患者。我们旨在评估SGLT2is在CKD患者中的疗效和安全性。
我们对随机对照试验进行了系统评价和荟萃分析。汇总平均差（MD）用于评估肾小球滤过率（eGFR）的下降情况以及尿白蛋白与肌酐比值（uACR）的变化。汇总风险比（HR）和率比（RR）用于评估肾脏结局和不良反应的综合情况。
共纳入30篇文章。eGFR下降率的总体MD为0.02（P = 0.05），倾向于SGLT2is组，差异接近显著；而uACR较基线的变化为-141.34mg/g，复合肾脏结局的风险比为0.64，显著有利于SGLT2is组。亚组分析显示，与安慰剂组相比，SGLT2is组中肾功能长期稳定的患者、基线有大量白蛋白尿的参与者以及4期CKD患者的eGFR下降率明显更慢。SGLT2is组生殖器霉菌感染和酮症酸中毒的风险显著高于安慰剂组。
对于CKD患者，无论是否患有糖尿病，我们的研究表明，SGLT2is在总体和长期阶段以及有大量白蛋白尿或4期CKD的患者中具有潜在的肾脏保护作用。然而，仅观察到SGLT2is组不良反应风险略有增加。因此，我们得出结论，在CKD患者中，使用SGLT2is是安全的且对肾脏有益。
