BACKGROUND The effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on kidney outcomes in patients with varying combinations of heart failure, chronic kidney disease, and type 2 diabetes mellitus have not been quantified. METHODS PubMed and Scopus were queried up to December 2023 for primary and secondary analysis of placebo-controlled trials of SGLT2i in patients with heart failure, chronic kidney disease, or type 2 diabetes mellitus. Outcomes of interest were composite kidney endpoint (combination of estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2, sustained doubling of serum creatinine, varying percent change in eGFR, and need for kidney replacement therapy), rate of eGFR slope decline and albuminuria progression. Hazard ratios (HR) and mean differences with their 95% confidence intervals (CI) were extracted onto an excel sheet, and the results were then pooled using a random-effect model through Review Manager (version 5.3, Cochrane Collaboration). RESULTS Eleven trials (n=80,928 patients) were included. Compared with the placebo, SGLT2i reduced the risk of the composite kidney endpoint by 41% (hazard ratio 0.59; 95%CI 0.42-0.83) in heart failure with reduced ejection fraction, 36% (hazard ratio 0.64;95%CI 0.55-0.73) in chronic kidney disease, and 38% (hazard ratio 0.62;95%CI 0.56-0.69) in type 2 diabetes mellitus. A similar pattern of benefit was observed in combinations of these comorbidities, as well as patients without baseline heart failure, chronic kidney disease, or type 2 diabetes mellitus. SGLT2i slowed the rate of eGFR slope decline and reduced the risk of sustained doubling of serum creatinine by 36% (hazard ratio 0.64; 95%CI 0.56-0.72) in the overall population, and a consistent effect on kidney outcomes was observed in most subpopulations with available data. CONCLUSIONS SGLT2i improved kidney outcomes in cohorts with heart failure, chronic kidney disease, and type 2 diabetes mellitus, and these effects were consistent across patients with different combinations of these comorbidities.

中文翻译：

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钠-葡萄糖协同转运蛋白 2 抑制剂对基线心血管-肾脏-代谢条件肾脏结果的影响：系统评价和荟萃分析。


背景钠-葡萄糖协同转运蛋白 2 抑制剂 （SGLT2i） 对心力衰竭、慢性肾病和 2 型糖尿病不同组合患者的肾脏结局的影响尚未量化。方法 检索了截至 2023 年 12 月的 PubMed 和 Scopus，以对心力衰竭、慢性肾病或 2 型糖尿病患者 SGLT2i 的安慰剂对照试验进行初级和次级分析。感兴趣的结局是复合肾脏终点 （估计肾小球滤过率 （eGFR） <15 mL/min/1.73 m2、血清肌酐持续加倍、eGFR 不同百分比变化和肾脏替代治疗需求的组合）、eGFR 斜率下降率和白蛋白尿进展。将风险比 （HR） 和平均差及其 95% 置信区间 （CI） 提取到 Excel 表格上，然后通过 Review Manager（5.3 版，Cochrane 协作网）使用随机效应模型将结果合并。结果 共纳入 11 项试验 （n=80,928 名患者）。与安慰剂相比，SGLT2i 将射血分数降低的心力衰竭复合肾终点风险降低了 41%（风险比 0.59;95% CI 0.42-0.83），射血分数降低 36%（风险比 0.64;95% CI 0.55-0.73），以及 38% （风险比 0.62;95% CI 0.56-0.69） 在 2 型糖尿病中。在这些合并症的组合以及没有基线心力衰竭、慢性肾病或 2 型糖尿病的患者中观察到类似的获益模式。SGLT2i 减缓了 eGFR 斜率下降的速度，并将血清肌酐持续加倍的风险降低了 36%（风险比 0.64;95% CI 0.56-0。72） 在总人群中，并且在大多数有可用数据的亚群中观察到对肾脏结果的一致影响。结论 SGLT2i 改善了心力衰竭、慢性肾病和 2 型糖尿病队列的肾脏结局，这些效果在患有这些合并症的不同组合的患者中是一致的。