Serum Potassium and Adverse Outcomes

Study Questions:

How do hypo- and hyperkalemia associate with the risks of all-cause mortality, cardiovascular (CV) mortality, and end-stage renal disease (ESRD)?

Methods:

The authors performed an individual-level data meta-analysis of 27 international cohorts in the CKD Prognosis Consortium, including 10 general population cohorts, seven high CV risk cohorts, and 10 chronic kidney disease (CKD) cohorts. Outcomes were all-cause mortality, CV mortality, and ESRD (defined as the initiation of renal replacement therapy). A two-stage meta-analysis was applied, with each study first analyzed individually, and followed by a random-effects meta-analysis. The relationship between baseline serum potassium levels and the outcomes were analyzed, adjusting for the covariates of age, race, gender, systolic blood pressure, antihypertensive drugs, total cholesterol, diabetes, body mass index, smoking, history of coronary artery disease or stroke, history of heart failure, estimated glomerular filtration rate (eGFR), and albuminuria.

Results:

Among the 27 cohorts, 1,217,986 participants were followed for a mean of 6.9 years (range 2.0-19 years). Mean age was 55 ± 16 years, 40% were women, and 14% were black. The average eGFR was 83 ± 23 ml/min/1.73 m2, and 17% had moderate to severe levels of albuminuria. The baseline potassium level was 4.2 ± 0.4 mmol/L. In the general and high CV risk cohorts, the prevalence of serum potassium >5.0 mmol/L, serum potassium >5.5 mmol/L, serum potassium <4.0 mmol/L, and serum potassium <3.5 mmol/L was 3.31% (95% confidence interval [CI], 3.28–3.34%), 0.49% (95% CI, 0.48–0.50%), 23.57% (95% CI, 23.49–23.64%), and 1.91% (95% CI, 1.89–1.94%) of individuals. In the CKD cohorts, the prevalence of serum potassium >5.0 mmol/L, serum potassium >5.5 mmol/L, serum potassium <4.0 mmol/L, and serum potassium <3.5 mmol/L was 17.94% (95% CI, 17.58–18.31%), 4.23% (95% CI, 4.03–4.42%), 12.61% (95% CI, 12.29–12.93%), and 2.03% (95% CI, 1.90–2.17%). The risk relationship between serum potassium level and all-cause mortality demonstrated the lowest risk with serum potassium levels between 4-4.5 mmol/L. Compared to the reference potassium level of 4.2 mmol/L, the adjusted hazard ratio (HR) for all-cause mortality was 1.22 (95% CI, 1.1-1.29) at serum potassium 5.5 mmol/L, and HR 1.49 (95% CI, 1.26-1.76) at serum potassium 3.0 mmol/L. This U-shaped relationship also held true for CV mortality and for the development of ESRD. The association of serum potassium with the studied outcomes was similar in people of different gender, race, history of diabetes, angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker use, and levels of albuminuria.

Conclusions:

Hypo- and hyperkalemia are associated with higher all-cause and CV mortality and with a higher risk of developing ESRD in a U-shaped relationship. In this meta-analysis, serum potassium levels of 4-4.5 mmol/L are associated with the best outcomes.

Perspective:

Abnormal serum potassium levels are a common and important electrolyte disturbance encountered in clinical practice. This international meta-analysis of over 1 million people described several important findings. Hypokalemia and hyperkalemia were relatively infrequent in populations with normal renal function; however, potassium levels outside of the range of 4.0-4.5 mmol/L were associated with significantly higher long-term risk of all-cause and CV mortality and ESRD. This U-shaped association builds upon findings from previous studies and extends them to a large, diverse outpatient population. Based on these data, one could argue for a randomized clinical trial to see if the correction of abnormal serum potassium in outpatients can improve mortality and/or the onset of ESRD.

Clinical Topics: Diabetes and Cardiometabolic Disease, Geriatric Cardiology, Prevention

Keywords: Albuminuria, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Diabetes Mellitus, Electrolytes, Geriatrics, Glomerular Filtration Rate, Hyperkalemia, Hypokalemia, Kidney Failure, Chronic, Metabolic Syndrome X, Potassium, Primary Prevention, Renal Insufficiency, Chronic, Renal Replacement Therapy, Risk


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