Population Epidemiology of Hyperkalemia: Cardiac and Kidney Long-term Health Outcomes

Abstract

Rationale & objective: The population burden and long-term implications of hyperkalemia have not been comprehensively studied. We studied how often and where hyperkalemia occurs as well as its independent association with survival and long-term cardiac and kidney health.

Study design: Population-based cohort study of adult residents of Grampian, United Kingdom.

Setting & participants: Among the 468,594 adult residents (2012-2014), 302,630 people with at least 1 blood test were followed until 2019.

Exposure: Hyperkalemia was defined as serum potassium ≥ 5.5 mmol/L. Adjustment for comorbidities, demographics, measures of acute and chronic kidney function, and medications prescribed before measurement of serum potassium.

Outcome: All-cause mortality, cardiac events, and kidney failure.

Analytical approach: Description of the annual incidence of hyperkalemia and the characteristics associated with its occurrence, and adjusted Cox proportional hazards (PH) analysis to evaluate the independent long-term association of hyperkalemia with all-cause mortality among people who survived ≥90 days after blood testing. Cause-specific PH models were fit to evaluate the association of hyperkalemia with cardiac events/death, noncardiac death, and kidney failure. Effect modification by level of estimated glomerular filtration rate (eGFR) at the time of blood testing was explored.

Results: The annual population incidence of hyperkalemia was 0.96 per 100 person-years. This represented 2.3%, 2.1%, and 1.9% of people with at least one blood test in 2012, 2013, and 2014, respectively. Two-thirds of episodes of hyperkalemia occurred in the community. The hyperkalemia rate was 2-fold higher for each 10-year greater age. Those with hyperkalemia were 20 times more likely to have concurrent acute kidney injury (AKI), and 17 times more likely to have an eGFR of <30 mL/min/1.73 m². Throughout 5 years of follow-up evaluation (2,483,452 person-years), hyperkalemia was associated with poorer health outcomes. This association held across all levels of kidney function and was irrespective of concurrent AKI, but was stronger among those with a baseline eGFR of ≥60 mL/min/1.73 m² (P for interaction < 0.001). The adjusted HRs (hyperkalemia vs no hyperkalemia) for people with eGFR ≥60 mL/min/1.73 m² and eGFR <30 mL/min/1.73 m² were 2.3 (95% CI, 2.2-2.5) and 1.5 (95% CI, 1.3-1.6) for mortality; 1.8 (95% CI, 1.6-1.9) and 1.4 (95% CI, 1.2-1.6) for cardiac events; and 17.0 (95% CI, 9.3-31.1) and 2.0 (95% CI, 1.5-2.8) for kidney failure, respectively.

Limitations: The observational nature of this study limits evaluation of causal relationships.

Conclusions: There is a substantial burden of hyperkalemia in the general population. Hyperkalemia is associated with poorer long-term health outcomes, especially kidney outcomes, that are independent of other established risk factors.

Keywords: Acute kidney injury (AKI); cardiovascular event; epidemiology; estimated glomerular filtration rate (eGFR); hyperkalemia; incidence; kidney; mortality; outcomes; potassium; renal function.