Supplementary Material for: Association of Dyskalemias with Ischemic Stroke in Advanced Chronic Kidney Disease Patients Transitioning to Dialysis

Introduction: Hypo- and hyperkalemia are associated with a higher risk of ischemic stroke. However, this association has not been examined in an advanced chronic kidney disease (CKD) population. Methods: From among 102,477 US veterans transitioning to dialysis between 2007 and 2015, 21,357 patients with 2 pre-dialysis outpatient estimated glomerular filtration rates 2 90–365 days apart and at least 1 potassium (K) each in the baseline and follow-up period were identified. We separately examined the association of both baseline time-averaged K (chronic exposure) and time-updated K (acute exposure) treated as categorized (hypokalemia [K 5.5 mEq/L] vs. referent [3.5–5.5 mEq/L]) and continuous exposure with time to the first ischemic stroke event prior to dialysis initiation using multivariable-adjusted Cox regression models. Results: A total of 2,638 (12.4%) ischemic stroke events (crude event rate 41.9 per 1,000 patient years; 95% confidence interval [CI] 40.4–43.6) over a median (Q1–Q3) follow-up time of 2.56 (1.59–3.89) years were observed. The baseline time-averaged K category of hypokalemia (adjusted hazard ratio [aHR], 95% CI: 1.35, 1.01–1.81) was marginally associated with a significantly higher risk of ischemic stroke. However, time-updated hyperkalemia was associated with a significantly lower risk of ischemic stroke (aHR, 95% CI: 0.82, 0.68–0.98). The exposure-outcome relationship remained consistent when using continuous K levels for both the exposures. Discussion/Conclusion: In patients with advanced CKD, hypokalemia (chronic exposure) was associated with a higher risk of ischemic stroke, whereas hyperkalemia (acute exposure) was associated with a lower risk of ischemic stroke. Further studies in this population are needed to explore the mechanisms underlying these associations.

引言：低钾血症与高钾血症均与缺血性脑卒中风险升高相关，但目前尚未在晚期慢性肾脏病（CKD）人群中探讨这一关联。
方法：本研究纳入2007年至2015年间102477名向透析过渡的美国退伍军人，最终筛选出21357名符合以下条件的患者：透析前门诊有两次估算肾小球滤过率检测，间隔90~365天，且基线期与随访期各至少有1次血钾（K）检测结果。我们分别采用分类变量（低钾血症[血钾＜3.5 mEq/L]、高钾血症[血钾＞5.5 mEq/L] vs. 参照组[3.5~5.5 mEq/L]）与连续变量两种方式，将基线时间平均血钾（慢性暴露）和随时间更新的血钾（急性暴露）作为暴露因素，通过多变量校正的Cox回归模型，分析透析启动前首次缺血性脑卒中事件发生时间与上述暴露因素的关联。
结果：本研究中位随访时间为2.56年（四分位距1.59~3.89年），共观察到2638例缺血性脑卒中事件，占总研究人群的12.4%；粗事件发生率为41.9例/1000患者年（95%置信区间[CI]：40.4~43.6）。基线时间平均血钾分类为低钾血症的患者，其缺血性脑卒中风险升高，关联具有临界统计学显著性（校正后风险比[aHR]：1.35，95%CI：1.01~1.81）。然而，随时间更新的高钾血症则与缺血性脑卒中风险显著降低相关（aHR：0.82，95%CI：0.68~0.98）。当采用连续血钾水平作为暴露因素时，暴露-结局的关联结果保持一致。
讨论与结论：在晚期慢性肾脏病患者中，慢性低钾血症暴露与缺血性脑卒中风险升高相关，而急性高钾血症暴露则与缺血性脑卒中风险降低相关。未来仍需针对该人群开展进一步研究，以阐明上述关联背后的潜在机制。