Risk of Hyperkalemia With Empagliflozin, Finerenone, or Both: Secondary Analysis of the CONFIDENCE Randomized Trial.

Sodium-glucose cotransporter 2 inhibitors might mitigate the risk of hyperkalemia with RASis.

钠-葡萄糖共转运蛋白2抑制剂可能会减轻与RASi相关的高钾血症风险。

This prespecified secondary analysis of the CONFIDENCE trial aimed to investigate the impact of empagliflozin, finerenone (a nonsteroidal mineralocorticoid receptor antagonist), and their combination on hyperkalemia, and whether hyperkalemia mediates albuminuria reduction in high-risk patients with chronic kidney disease and type 2 diabetes with albuminuria.

这项预先指定的CONFIDENCE试验的次要分析旨在研究恩格列净、非甾体矿物皮质激素受体拮抗剂finerenone及其联合使用对高钾血症的影响，以及高钾血症是否介导了慢性肾脏病和2型糖尿病伴有白蛋白尿的高风险患者白蛋白尿的减少。

Methods

In this double-blind, randomized, controlled trial, CONFIDENCE, patients with type 2 diabetes, chronic kidney disease (estimated glomerular filtration rate: 30-90 mL/min/1.73 m2), and albuminuria (urine albumin-to-creatinine ratio [UACR]: 100-5,000 mg/g) on stable doses of RASis were randomized 1:1:1 to empagliflozin, finerenone, or both.

在这项双盲、随机、对照试验CONFIDENCE中，患有2型糖尿病、慢性肾脏病（估算肾小球滤过率：30-90 mL/min/1.73 m2）和白蛋白尿（尿白蛋白与肌酐比值[UACR]：100-5,000 mg/g）的患者，在稳定剂量的RAS抑制剂治疗下，被随机分为1:1:1接受恩格列净、finerenone或两者联合治疗。

The primary outcome was change in UACR from baseline to Day 180.

主要结果是基线至第180天尿白蛋白/肌酐比值(UACR)的变化。

Mean changes in potassium were estimated using linear mixed models.

使用线性混合效应模型估计钾的平均变化。

Logistic regression models assessed the risk of moderate (serum potassium >5.5 mmol/L) and severe (serum potassium >6.0 mmol/L) hyperkalemia.

逻辑回归模型评估了中度（血清钾>5.5 mmol/L）和重度（血清钾>6.0 mmol/L）高钾血症的风险。

Causal mediation analysis was used to ascertain the impact of hyperkalemia on mean UACR change at Day 180.

因果中介分析用于确定高钾血症对第180天平均尿白蛋白/肌酐比率（UACR）变化的影响。

Results

Patients developing hyperkalemia had lower estimated glomerular filtration rate, higher potassium, and more severe albuminuria at baseline.

发展为高钾血症的患者在基线时估算的肾小球滤过率较低，血钾较高，且蛋白尿更为严重。

Hyperkalemia events accumulated over the 180 days of the trial in all 3 groups.

在为期180天的试验中，所有3组累积了高钾血症事件。

There were few treatment discontinuations.

治疗中断的情况很少。

Randomization to finerenone was associated with increase in serum potassium.

随机分配至非奈利酮治疗的患者血清钾水平有所增加。

No difference was seen between combination treatment and finerenone in mean change in serum potassium (P = 0.91) or the odds of developing hyperkalemia (P = 0.85).

在血清钾平均变化或发展高钾血症的几率上，联合治疗与finerenone之间没有差异（P = 0.91和P = 0.85）。

Overall, hyperkalemia occurred in 113 patients (14.5%): 40 of 265 (15.1%) with combination therapy, 48 of 255 (18.8%) with finerenone, and 25 of 259 (9.7%) with empagliflozin.

总体而言，高钾血症发生在113名患者（14.5%）中：联合治疗组265名患者中有40例（15.1%），finerenone组255名患者中有48例（18.8%），empagliflozin组259名患者中有25例（9.7%）。

Hyperkalemia was not in the causal pathway of UACR reduction at Day 180.

在第180天，高钾血症并非尿白蛋白肌酐比值（UACR）降低的因果路径。

Conclusions

Over 180 days, the combination of empagliflozin and finerenone did not significantly mitigate the risk of hyperkalemia.

在180天的观察期内，恩格列净和非利酮的联合使用并未显著降低高钾血症的风险。

The treatment effect was maintained regardless of development of hyperkalemia.

无论是否发展为高钾血症，治疗效果都得以维持。

(Combination Effect of Finerenone and Empagliflozin in Participants with Chronic Kidney Disease and Type 2 Diabetes Using a Urinary Albumin-to-Creatinine Ratio Endpoint [CONFIDENCE]; NCT05254002).

（联合使用Finerenone和Empagliflozin在慢性肾脏病和2型糖尿病患者中的效果研究，以尿白蛋白与肌酐比值为终点 [CONFIDENCE]；NCT05254002）。