In CKD, hyperkalemia more strongly associated with mortality than cardiovascular events
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Between 11% and 17% of patients with chronic kidney disease developed chronic hyperkalemia, which was more consistently associated with death than with major adverse cardiovascular events, findings from an observational study showed.
For the study, investigators from Sweden included 36,511 patients with CKD stages G3 through G5 and examined the trajectories of abnormal potassium levels to assess the frequency of hyperkalemia, chronic and transient, and its relationship with major adverse cardiovascular events (MACE) and mortality.
“ ... We observed associations between patterns of [hyperkalemia and hypokalemia] and outcomes in a large cohort of patients with CKD G3 [through] 5,” Marco Trevisan and colleagues wrote in the study published in the Clinical Kidney Journal. “These associations tended to be stronger and more consistent for death than for MACE. This is counter to the theoretical model that suggests that hyperkalemia leads to death mediated by MACE and demonstrates a lack of specificity.”
When assessing each patient’s monthly potassium levels, researchers created a rolling assessment of the amount of time potassium levels were abnormal for the previous 12 months and found that with potassium levels greater than 5 mmol/L, the patterns of hyperkalemia were transient less than or equal to 50% of the time and were chronic more than 50% of the time.
When assessing the percentage of patients with CKD G4 to G5 who experienced chronic hyperkalemia, researchers also noted that previous patterns of dyskalemia and the current potassium values in assessed patients were both reportedly associated with the risk of MACE and death.
“When both metrics are introduced in the same model, patterns of hyperkalemia (transient and chronic), but not current hyperkalemia, remained associated with the risk of MACE,” the researchers wrote. “Likewise, the transient hyperkalemia pattern, and current hyperkalemia, but not the chronic hyperkalemia pattern, were associated with the risk of death.”
The study found male sex, diabetes and vascular disease were potential risk factors for chronic and transient hyperkalemia. Researchers also found hyperkalemia was a “direct effect” of renin-angiotensin-aldosterone system inhibitor use.
Researchers also noted hyperkalemia patterns were higher in patients with a lower estimated glomerular filtration rate, a finding in line with previous studies.
“A given physiological disturbance is more likely to cause hyperkalemia in someone with CKD G4 [to] 5 than someone with more normal kidney function,” Trevisan and colleagues wrote. “Many physiological disturbances are subclinical and may not be captured in administrative data such as ours. In patients with advanced CKD, smaller perturbations in physiology lead to hyperkalemia and the magnitude of the subsequent risk is more related to the magnitude of the perturbation than causally related to the hyperkalemia.”
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