Department of Nephrology, The Second People's Hospital of Hunan Province, Changsha City, Hunan Province, China.
Department of Nephrology, People's Hospital of Ningxiang City, Ningxiang City, Hunan Province, China.
BMC Nephrol. 2024 Nov 1;25(1):392. doi: 10.1186/s12882-024-03833-2.
This meta-analysis was designed to investigate cardio-renal outcomes and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) as a therapeutic option among chronic kidney disease(CKD) patients with GFR < 60 mL/min/1.73 m2, regardless of their diabetic status.
We conducted a full-scale search from MEDLINE, EMBASE and the Cochrane Library database to identify eligible studies up to Jun 2024. All randomized controlled trials (RCTs) comparing cardio-renal outcomes and/or safety of SGLT2i in CKD patients with eGFR < 60 mL/min/1.73 m were involved. The relative risk (RR) and 95% confidence interval (CI) for primary outcomes and adverse events were computed by random-effects mode. We used I statistic to analyze heterogeneity. Publication bias was assessed by Egger's test.
Our study incorporated 17 RCTS, including 27,928 patients. In CKD patients with eGFR < 60 mL/min/1.73 m, SGLT2i decreased risks of cardiovascular events (seven studies, 17,355 participants, RR 0.77, 95% CI 0.70-0.84), hospitalization for heart failure (HHF) (seven studies, 17,869 participants, RR 0.73, 95% CI 0.65-0.82), cardiovascular death (eight studies, 23,079 participants, RR 0.81, 95% CI 0.74 to 0.88) and renal composite outcomes (eight studies, 22,525 participants, RR 0.70, 95% CI 0.61-0.80) with lower risks of any serious adverse effects(fourteen studies, 19,654 participants, RR 0.91, 95% CI 0.87-0.95), hypoglycemia (nine studies, 16,412 participants, RR 0.91, 95% CI 0.84-0.98), hyperkalemia (four studies, 2693 participants, RR 0.68, 95% CI 0.51-0.93) and acute renal injury (five studies, 5424 participants, RR 0.79, 95% CI 0.65-0.95) compared to placebo. SGLT2i also slowed eGFR decline (total slopes: five studies, 10,370 participants, mean difference 1.17, 95%CI 0.86-1.49; chronic slopes: four studies, 8459 participants, mean difference 2.12, 95%CI 1.64-2.61). Further subgroup analyses revealed that SGLT2i decreased relative risks of cardiovascular outcomes(three studies, 1075 participants, RR 0.76, 95% CI 0.54-0.82), HHF(four studies, 1280 participants, RR 0.74, 95% CI 0.55-1.00) and renal composite outcomes (six studies,4375 participants, RR 0.78, 95% CI 0.68-0.88) with no increased adverse events in the CKD 4 patients.
SGLT2i significantly improved cardio-renal outcomes and were generally safe in CKD patients with eGFR < 60 mL/min/1.73 m2 and with eGFR < 30 mL/min/1.73 m2. Future large-scale RCTs are needed to confirm the robustness of these results.
本荟萃分析旨在探讨钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）在肾小球滤过率（eGFR）<60 mL/min/1.73 m2 的慢性肾脏病（CKD）患者中的心脏-肾脏结局和安全性，无论其糖尿病状态如何。
我们从 MEDLINE、EMBASE 和 Cochrane 图书馆数据库中进行了全面搜索，以确定截至 2024 年 6 月的合格研究。所有比较 SGLT2i 在 eGFR<60 mL/min/1.73 m 的 CKD 患者中的心脏-肾脏结局和/或安全性的随机对照试验（RCT）均被纳入。使用随机效应模型计算主要结局和不良事件的相对风险（RR）和 95%置信区间（CI）。我们使用 I 统计量分析异质性。使用 Egger 检验评估发表偏倚。
我们的研究纳入了 17 项 RCT，共 27928 名患者。在 eGFR<60 mL/min/1.73 m 的 CKD 患者中，SGLT2i 降低了心血管事件（7 项研究，17355 名参与者，RR 0.77，95%CI 0.70-0.84）、心力衰竭住院（7 项研究，17869 名参与者，RR 0.73，95%CI 0.65-0.82）、心血管死亡（8 项研究，23079 名参与者，RR 0.81，95%CI 0.74-0.88）和肾脏复合结局（8 项研究，22525 名参与者，RR 0.70，95%CI 0.61-0.80）的风险，同时降低了任何严重不良事件（14 项研究，19654 名参与者，RR 0.91，95%CI 0.87-0.95）、低血糖（9 项研究，16412 名参与者，RR 0.91，95%CI 0.84-0.98）、高钾血症（4 项研究，2693 名参与者，RR 0.68，95%CI 0.51-0.93）和急性肾损伤（5 项研究，5424 名参与者，RR 0.79，95%CI 0.65-0.95）的风险。与安慰剂相比，SGLT2i 还减缓了 eGFR 下降（总斜率：5 项研究，10370 名参与者，平均差异 1.17，95%CI 0.86-1.49；慢性斜率：4 项研究，8459 名参与者，平均差异 2.12，95%CI 1.64-2.61）。进一步的亚组分析表明，SGLT2i 降低了心血管结局（3 项研究，1075 名参与者，RR 0.76，95%CI 0.54-0.82）、心力衰竭住院（4 项研究，1280 名参与者，RR 0.74，95%CI 0.55-1.00）和肾脏复合结局（6 项研究，4375 名参与者，RR 0.78，95%CI 0.68-0.88）的相对风险，同时在 eGFR<30 mL/min/1.73 m 的 CKD 患者中没有增加不良事件。
SGLT2i 显著改善了 eGFR<60 mL/min/1.73 m2 且 eGFR<30 mL/min/1.73 m2 的 CKD 患者的心脏-肾脏结局，且总体安全性良好。需要进一步的大规模 RCT 来证实这些结果的稳健性。
