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

https://doi.org/10.1053/j.ajkd.2021.07.008Get rights and content

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.

Section snippets

Methods

We reported this study according to the STROBE guidelines.29 Permissions for the use of unconsented, pseudonymized, routinely collected health data were provided by North of Scotland Research Ethics Committee (18/NS/0051), Grampian Caldicott guardian, and National Health Service (NHS) Research and Development.

Annual Incidence of Hyperkalemia

Over a 3-year period of monitoring adults at risk within the Grampian population, we identified 13,482 people with a first hyperkalemia event at a threshold of potassium ≥5.5 mmol/L (Table 1). Using alternative hyperkalemia thresholds, there were 59,571 first hyperkalemia events at ≥5.0 mmol/L, 4,491 at ≥6.0 mmol/L, and 2,016 at ≥6.5 mmol/L. These definitions corresponded to respective annual incidence rates per 100 person-years of 0.96 (95% CI, 0.94-0.98) at ≥5.5 mmol/L versus 4.24 (95% CI,

Discussion

Although hyperkalemia is a recognized clinical emergency, the full population burden, context, and long-term implications of hyperkalemia have not been comprehensively studied. In this full regional population with complete capture of all blood potassium values, clinical contexts, and health outcomes, this analysis provides evidence of a greater burden related to hyperkalemia than reported in the previous literature. By capturing laboratory measures of hyperkalemia in all settings (hospital and

Article Information

Authors’ Full Names and Academic Degrees

Andrew Mclean, MBChB, Mintu Nath, PhD, and Simon Sawhney, MBChB, PhD.

Authors’ Contributions

Research idea and study design: AM, SS; data acquisition: SS; data analysis/interpretation: AM, MN, SS; statistical analysis: SS; supervision or mentorship: SS. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated

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