Predictors for repeated hyperkalemia and potassium trajectories in high-risk patients - A population-based cohort study

PLoS One. 2019 Jun 21;14(6):e0218739. doi: 10.1371/journal.pone.0218739. eCollection 2019.


Understanding predictors and trajectories of increased potassium may inform testing and treatment of hyperkalemia. We examined predictors for repeated hyperkalemia among patients after first-time renin angiotensin system inhibitor (RASi) prescription, chronic kidney disease (CKD), or chronic heart failure (CHF); and we also examined potassium trajectories in these patients after their first hyperkalemia event. We used Danish population-based registries to identify all patients with first-time RASi prescription, incident CKD, or incident CHF (2000-2012). For patients with a first hyperkalemia event, potassium trajectories over the following 6 months were examined. The predictors associated with repeated hyperkalemia were assessed, with repeated hyperkalemia defined as a potassium test >5.0 mmol/L after the first event within 6 months. Overall 262,375 first-time RASi users, 157,283 incident CKD patients, and 14,600 incident CHF patients were included. Of patients with a first hyperkalemia event, repeated hyperkalemia within 6 months occurred in 37% of RASi users, 40% with CKD, and 49% of patients with CHF. Predictors included severe hyperkalemia, low eGFR, diabetes, and spironolactone use. In all cohorts, the median potassium levels declined over 2-4 weeks after a hyperkalemia event for the first time, but reverted to levels higher than before the initial hyperkalemia event in those who had repeated hyperkalemia. Following hyperkalemia, discontinuation of RASi and spironolactone was common in the RASi and CHF cohorts. Repeated hyperkalemia was common among the explored cohorts. The first hyperkalemia event was an indicator of increased median potassium levels. Predictors may identify patients likely to benefit from intensified monitoring and intervention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiotensin Receptor Antagonists / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Cohort Studies
  • Denmark / epidemiology
  • Diabetes Complications / blood
  • Diabetes Complications / chemically induced
  • Diabetes Complications / diagnosis
  • Diabetes Complications / epidemiology
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / diagnosis
  • Diabetes Mellitus / epidemiology
  • Female
  • Heart Failure / blood
  • Heart Failure / complications
  • Heart Failure / epidemiology
  • Humans
  • Hyperkalemia / chemically induced
  • Hyperkalemia / diagnosis*
  • Hyperkalemia / epidemiology*
  • Hyperkalemia / etiology*
  • Male
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists / adverse effects
  • Potassium / blood*
  • Prevalence
  • Prognosis
  • Recurrence
  • Registries
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / epidemiology
  • Renin-Angiotensin System / drug effects
  • Risk Factors


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Mineralocorticoid Receptor Antagonists
  • Potassium

Grants and funding

This work was supported by an institutional research grant from AstraZeneca to Aarhus University and by the Program for Clinical Research Infrastructure (PROCRIN) established by the Lundbeck Foundation and the Novo Nordisk Foundation. While AstraZeneca was involved in the study’s concept, it was designed and conducted by the coauthors from Aarhus University. The funder provided support in the form of salaries for authors (P.H and E.P), but the funder did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of the aforementioned authors are articulated in the ‘author contributions’ section.