Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan.
Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka, Japan.
J Am Soc Nephrol. 2024 Oct 1;35(10):1391-1401. doi: 10.1681/ASN.0000000000000425. Epub 2024 Jun 18.
Restarting renin-angiotensin system inhibitor after discontinuation was associated with a lower risk of kidney outcomes and mortality but not related to hyperkalemia. Our findings support a proactive approach to restarting renin-angiotensin system inhibitor among patients with CKD.
While renin-angiotensin system inhibitors (RASi) have been the mainstream treatment for patients with CKD, they are often discontinued because of adverse effects such as hyperkalemia and AKI. It is unknown whether restarting RASi after discontinuation improves clinical outcomes.
Using the Osaka Consortium for Kidney disease Research database, we performed a target trial emulation study including 6065 patients with an eGFR of 10–60 ml/min per 1.73 m who were followed up by nephrologists and discontinued RASi between 2005 and 2021. With a clone-censor-weight approach, we compared a treatment strategy for restarting RASi within a year after discontinuation with that for not restarting RASi. Patients were followed up for 5 years at maximum after RASi discontinuation. The primary outcome was a composite kidney outcome (initiation of KRT, a ≥50% decline in eGFR, or kidney failure [eGFR <5 ml/min per 1.73 m]). Secondary outcomes were all-cause death and incidence of hyperkalemia (serum potassium levels ≥5.5 mEq/L).
Among those who discontinued RASi (mean [SD] age 66 [15] years, 62% male, mean [SD] eGFR 40 [26] ml/min per 1.73 m), 2262 (37%) restarted RASi within a year. Restarting RASi was associated with a lower hazard of the composite kidney outcome (hazard ratio [HR], 0.85; 95% confidence intervals [CIs], 0.78 to 0.93]) and all-cause death (HR, 0.70; 95% CI, 0.61 to 0.80) compared with not restarting RASi. The incidence of hyperkalemia did not differ significantly between the two strategies (HR, 1.11; 95% CI, 0.96 to 1.27).
Restarting RASi after discontinuation was associated with a lower risk of kidney outcomes and mortality but not related to the incidence of hyperkalemia.
停用肾素-血管紧张素系统抑制剂（RASi）后重新开始使用与较低的肾脏结局和死亡率风险相关，但与高钾血症无关。我们的研究结果支持在 CKD 患者中积极重新开始使用 RASi。
虽然 RASi 一直是 CKD 患者的主流治疗方法，但由于高钾血症和 AKI 等不良反应，它们经常被停用。尚不清楚停用后重新开始使用 RASi 是否能改善临床结局。
利用大阪肾病研究联盟数据库，我们进行了一项目标试验模拟研究，纳入了 6065 例 eGFR 为 10-60 ml/min/1.73m 的患者，这些患者由肾病医生随访，在 2005 年至 2021 年间停用了 RASi。我们采用克隆 censoring-weight 方法，比较了停用后一年内重新开始使用 RASi 的治疗策略与不重新开始使用 RASi 的治疗策略。在 RASi 停用后，患者的随访时间最长可达 5 年。主要结局是复合肾脏结局（开始 KRT、eGFR 下降≥50%或肾脏衰竭[eGFR<5 ml/min/1.73m]）。次要结局是全因死亡和高钾血症（血清钾水平≥5.5 mEq/L）的发生率。
在停用 RASi 的患者中（平均[标准差]年龄 66[15]岁，62%为男性，平均[eGFR]40[26]ml/min/1.73m），有 2262 例（37%）在一年内重新开始使用 RASi。与未重新开始使用 RASi 相比，重新开始使用 RASi 与较低的复合肾脏结局风险（风险比[HR]，0.85；95%置信区间[CI]，0.78 至 0.93）和全因死亡风险（HR，0.70；95%CI，0.61 至 0.80）相关。两种策略之间高钾血症的发生率没有显著差异（HR，1.11；95%CI，0.96 至 1.27）。
停用后重新开始使用 RASi 与较低的肾脏结局和死亡率风险相关，但与高钾血症的发生率无关。
