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 <30 mL/min/1.73 m2 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 <3.5 mEq/L] and hyperkalemia [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.