Serum potassium and adverse outcomes across the range of kidney function: a CKD Prognosis Consortium meta-analysis

Abstract

Aims: Both hypo- and hyperkalaemia can have immediate deleterious physiological effects, and less is known about long-term risks. The objective was to determine the risks of all-cause mortality, cardiovascular mortality, and end-stage renal disease associated with potassium levels across the range of kidney function and evaluate for consistency across cohorts in a global consortium.

Methods and results: We performed an individual-level data meta-analysis of 27 international cohorts [10 general population, 7 high cardiovascular risk, and 10 chronic kidney disease (CKD)] in the CKD Prognosis Consortium. We used Cox regression followed by random-effects meta-analysis to assess the relationship between baseline potassium and adverse outcomes, adjusted for demographic and clinical characteristics, overall and across strata of estimated glomerular filtration rate (eGFR) and albuminuria. We included 1 217 986 participants followed up for a mean of 6.9 years. The average age was 55 ± 16 years, average eGFR was 83 ± 23 mL/min/1.73 m2, and 17% had moderate- to-severe increased albuminuria levels. The mean baseline potassium was 4.2 ± 0.4 mmol/L. The risk of serum potassium of >5.5 mmol/L was related to lower eGFR and higher albuminuria. The risk relationship between potassium levels and adverse outcomes was U-shaped, with the lowest risk at serum potassium of 4-4.5 mmol/L. Compared with a reference of 4.2 mmol/L, the adjusted hazard ratio for all-cause mortality was 1.22 [95% confidence interval (CI) 1.15-1.29] at 5.5 mmol/L and 1.49 (95% CI 1.26-1.76) at 3.0 mmol/L. Risks were similar by eGFR, albuminuria, renin-angiotensin-aldosterone system inhibitor use, and across cohorts.

Conclusions: Outpatient potassium levels both above and below the normal range are consistently associated with adverse outcomes, with similar risk relationships across eGFR and albuminuria.

Figure 1

Distribution of serum potassium concentrations, overall and by baseline estimated glomerular filtration rate in the general population and high cardiovascular risk cohorts.

Figure 2

Continuous association of estimated glomerular filtration rate (A) and albuminuria (B) with the risk of serum potassium level >5.5 mmol/L and of estimated glomerular filtration rate (C) and albuminuria (D) with the risk of serum potassium level <3.5 mmol/L, in the general population and high cardiovascular risk cohorts. Black dots indicate statistical significance compared with the reference (diamond) estimated glomerular filtration rate of 80 mL/min/1.73 m² (A and C) and albuminuria of 10 mg/g (B and D). Adjusted for age, gender, race, systolic blood pressure, antihypertensive drugs, total cholesterol, diabetes, body mass index, smoking, history of coronary heart disease or stroke, and history of heart failure.

Figure 3

Adjusted hazard ratio of all-cause mortality, cardiovascular mortality, and end-stage renal disease associated with serum potassium concentration in the general population and high cardiovascular risk cohorts. Black dots indicate statistical significance compared with the reference (diamond) serum potassium of 4.2 mmol/L. Models adjusted for age, gender, race, systolic blood pressure, antihypertensive drugs, total cholesterol, diabetes, body mass index, smoking, estimated glomerular filtration rate, albuminuria, history of coronary heart disease or stroke, and history of heart failure.

Figure 4

Adjusted relative hazard of all-cause mortality for potassium of 3.0 mmol/L (A) and 5.5 mmol/L (B) compared with a potassium of 4.2 mmol/L in individual general population/high cardiovascular risk cohorts.