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

Abstract

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. Population-based cohort study of adult residents of Grampian, United Kingdom. Among the 468,594 adult residents (2012-2014), 302,630 people with at least 1 blood test were followed until2019. 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. All-cause mortality, cardiac events, and kidney failure. Description of the annual incidence of hyperkalemia and the characteristics associated with its occurrence, and adjusted Cox proportional hazards (PH) analysis to evaluate theindependent 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. 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. The observational nature of this study limits evaluation of causal relationships. 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.