Incidence of and risk factors for newly diagnosed hyperkalemia after hospital discharge in non-dialysis-dependent CKD patients treated with RAS inhibitors

IntroductionRenin-angiotensin system (RAS) inhibitors have been increasingly prescribed due to their beneficial effects on end-organ protection. Iatrogenic hyperkalemia is a well-known life-threatening complication of RAS inhibitor use in chronic kidney disease (CKD) patients. We hypothesized that CKD patients treated with RAS inhibitors frequently develop hyperkalemia after hospital discharge even if they were normokalemic during their hospitalization because their lifestyles change substantially after discharge. The present study aimed to examine the incidence of newly diagnosed hyperkalemia, the timing of hyperkalemia, and its risk factors in CKD patients treated with RAS inhibitors at the time of hospital discharge.MethodsWe retrospectively enrolled patients aged 20 years or older with CKD G3-5 (estimated glomerular filtration rate 2) and who were treated with RAS inhibitors and discharged from St. Luke’s International Hospital between July 2011 and December 2015. Patients who were under maintenance dialysis or had hyperkalemic events before discharge were excluded. Data regarding the patients’ age, sex, CKD stage, diabetes mellitus status, malignancy status, combined use of RAS inhibitors, concurrent medication, and hyperkalemic events after discharge were extracted from the hospital database. Our primary outcome was hyperkalemia, defined as serum potassium ≥ 5.5 mEq/L. Multiple logistic regression and Kaplan-Meier analyses were performed to identify the risk factors for and the timing of hyperkalemia, respectively.ResultsAmong the 986 patients, 121 (12.3%) developed hyperkalemia after discharge. In the regression analysis, relative to CKD G3a, G3b [odds ratio (OR): 1.88, 95% confidence interval 1.20–2.97] and G4-5 (OR: 3.40, 1.99–5.81) were significantly associated with hyperkalemia. The use of RAS inhibitor combinations (OR: 1.92, 1.19–3.10), malignancy status (OR: 2.10, 1.14–3.86), and baseline serum potassium (OR: 1.91, 1.23–2.97) were also significantly associated with hyperkalemia. The Kaplan-Meier analysis showed that hyperkalemia was most frequent during the early period after discharge, particularly within one month.ConclusionHyperkalemia was frequent during the early period after discharge among previously normokalemic CKD patients who were treated with RAS inhibitors. Appropriate follow-up after discharge should be required for these patients, particularly those with advanced CKD or malignancy status, such as hematological malignancy or late-stage malignancy, and those who are treated with multiple RAS inhibitors.

引言：肾素-血管紧张素系统（RAS）抑制剂因其对终末器官的保护作用，临床处方量日益增加。医源性高钾血症是慢性肾脏病（CKD）患者使用RAS抑制剂时常见的致命并发症。我们提出假设：尽管使用RAS抑制剂的慢性肾脏病患者在住院期间血钾水平正常，但由于出院后生活方式发生显著改变，这类患者常在出院后出现高钾血症。本研究旨在探讨出院时接受RAS抑制剂治疗的慢性肾脏病患者中，新发高钾血症的发生率、发病时间及其危险因素。

方法：本研究回顾性纳入2011年7月至2015年12月期间在圣路加国际医院出院、年龄≥20岁、符合CKD G3-5分期且接受RAS抑制剂治疗的患者。排除接受维持性透析或出院前已发生高钾血症事件的患者。从医院数据库中提取患者的年龄、性别、CKD分期、糖尿病患病情况、恶性肿瘤患病情况、RAS抑制剂联合使用情况、合并用药情况以及出院后高钾血症事件相关数据。本研究的主要结局为高钾血症，定义为血清钾≥5.5 mEq/L。分别采用多因素logistic回归分析与Kaplan-Meier分析，以明确高钾血症的危险因素与发病时间。

结果：在986例纳入研究的患者中，121例（12.3%）在出院后发生了高钾血症。回归分析结果显示，相较于CKD G3a分期患者，G3b分期[比值比（odds ratio, OR）=1.88，95%置信区间（confidence interval, CI）：1.20~2.97]与G4-5分期（OR=3.40，95%CI：1.99~5.81）患者发生高钾血症的风险显著升高。RAS抑制剂联合用药（OR=1.92，95%CI：1.19~3.10）、恶性肿瘤患病情况（OR=2.10，95%CI：1.14~3.86）以及基线血清钾水平（OR=1.91，95%CI：1.23~2.97）也与高钾血症的发生显著相关。Kaplan-Meier分析结果显示，高钾血症多发生在出院后早期阶段，尤其是出院后1个月内。

结论：对于住院期间血钾正常、出院后接受RAS抑制剂治疗的慢性肾脏病患者，高钾血症在出院后早期较为常见。此类患者出院后应接受恰当的随访监测，尤其是合并晚期慢性肾脏病、恶性肿瘤（如血液系统恶性肿瘤或晚期恶性肿瘤）以及接受多种RAS抑制剂治疗的患者。