Abstract：
It is unknown whether initiating diuretics on top of renin-angiotensin system inhibitors (RASi) is superior to alternative antihypertensive agents such as calcium channel blockers (CCBs) in patients with chronic kidney disease (CKD). For this purpose, we emulated a target trial in the Swedish Renal Registry 2007-2022 that included nephrologist-referred patients with moderate-advanced CKD and treated with RASi, who initiated diuretics or CCB. Using propensity score-weighted cause-specific Cox regression, we compared risks of major adverse kidney events (MAKE; composite of kidney replacement therapy [KRT], experiencing over a 40% eGFR decline from baseline, or an eGFR under 15 ml/min per 1.73m2), major cardiovascular events (MACE; composite of cardiovascular death, myocardial infarction or stroke), and all-cause mortality. We identified 5875 patients (median age 71 years, 64% men, median eGFR 26 ml/min per 1.73m2), of whom 3165 started a diuretic and 2710 a CCB. After a median follow-up of 6.3 years, 2558 MAKE, 1178 MACE and 2299 deaths occurred. Compared to CCB, diuretic use was associated with a lower risk of MAKE (weighted hazard ratio 0.87 [95% confidence interval: 0.77-0.97]), consistent across single components (KRT: 0.77 [0.66-0.88], over 40% eGFR decline: 0.80 [0.71-0.91] and eGFR under 15ml/min/1.73m2: 0.84 [0.74-0.96]). The risks of MACE (1.14 [0.96-1.36]) and all-cause mortality (1.07 [0.94-1.23]) did not differ between therapies. Results were consistent when modeling the total time drug exposure, across sub-groups and a broad range of sensitivity analyses. Thus, our observational study suggests that in patients with advanced CKD, using a diuretic rather than a CCB on top of RASi may improve kidney outcomes without compromising cardioprotection.
摘要：
在慢性肾病（CKD）患者中，在肾素-血管紧张素系统抑制剂（RASi）的基础上使用利尿剂是否优于其他抗高血压药，例如钙通道阻滞剂（CCB）。为此,我们仿效了2007-2022年瑞典肾脏注册中心的一项目标试验，该试验包括中晚期CKD且接受RASi治疗的肾病医师转诊患者，谁开始利尿剂或CCB。使用倾向得分加权原因特异性Cox回归，我们比较了主要不良肾脏事件的风险(MAKE；肾脏替代疗法的复合[KRT]，经历了超过40%的eGFR从基线下降，或每1.73m2低于15ml/min的eGFR)，主要心血管事件(MACE；心血管死亡的复合，心肌梗塞或中风)，和死亡。我们确定了5875例患者（中位年龄71岁，64%的男性,每1.73m2中值eGFR26ml/min)，其中3165人开始服用利尿剂，2710人开始服用CCB。经过6.3年的中位随访，2558MAKE,发生了1178例MACE和2299例死亡。与建行相比,利尿剂使用与MAKE风险较低相关(加权风险比0.87[95%置信区间:0.77-0.97]),在单个组件之间一致(KRT：0.77[0.66-0.88]，eGFR下降40%以上：0.80[0.71-0.91]，eGFR在15ml/min/1.73m2以下：0.84[0.74-0.96]）。MACE的风险（1.14[0.96-1.36]）和全因死亡率（1.07[0.94-1.23]）在治疗之间没有差异。模拟药物暴露的总时间时，结果是一致的，跨小组和广泛的敏感性分析。因此，我们的观察性研究表明，在晚期CKD患者中，在RASi基础上使用利尿剂而不是CCB可能在不损害心脏保护的情况下改善肾脏结局.
