What is the clinical evidence from this study?

Study design: Cohort. Population: Chronic Kidney Disease (n=55266). Intervention: Abnormal serum potassium (≥6.0 mEq/L or <3.5 mEq/L) vs. Normal serum potassium (4.5-4.9 mEq/L). Primary outcome: Mortality (aIRR 3.31, 95% CI 2.52 to 4.34, p=<0.001).

October 23, 2015Open Access

Association between Serum Potassium and Outcomes in Patients with Reduced Kidney Function

Q: What are the key findings of this study?

Hyperkalemia (≥6.0 mEq/L) and hypokalemia (<3.5 mEq/L) were independently associated with higher mortality in CKD patients, with adjusted incidence rate ratios of 3.31 and 3.05, respectively.

Key Result

Hyperkalemia (≥6.0 mEq/L) and hypokalemia (<3.5 mEq/L) were independently associated with higher mortality in CKD patients, with adjusted incidence rate ratios of 3.31 and 3.05, respectively.

Study Design

Type

Cohort (n=55,266)

Multicenter

Structured PICO

Does abnormal serum potassium (hyperkalemia or hypokalemia) increase the risk of mortality, MACE, hospitalization, and RAAS blocker discontinuation in patients with CKD?

Population

55,266 adults (aged ≥18 years) with CKD (eGFR <60 ml/min per 1.73 m²) not undergoing dialysis or prior kidney transplant, from a managed care organization in California, USA.

Intervention

Abnormal serum potassium levels (time-updated exposure categorized as <3.5, 3.5-3.9, 4.0-4.4, 5.0-5.4, 5.5-5.9, and ≥6.0 mEq/L)

Comparator

Normal serum potassium levels (referent category of 4.5-4.9 mEq/L)

Outcome

All-cause death, hospitalizations, MACE (composite of arrhythmia, myocardial infarction, stroke, and heart failure exacerbation), and RAAS blocker discontinuationcomposite

Both hyperkalemia and hypokalemia are independently associated with higher rates of death, MACE, hospitalization, and RAAS blocker discontinuation in patients with CKD not undergoing dialysis.

Main Result

Effect estimate: aIRR 3.31 (95% CI 2.52 to 4.34)

p-value: p=<0.001

Limitations

Potential confounding by unconsidered factors
Lack of data on nutritional status, height, and proteinuria
Amnestic to potassium values during hospitalizations
All patients were treated within a single healthcare-providing organization
Could not consider over-the-counter treatments
Observational study design does not allow for causal interpretation

Abstract

BACKGROUND AND OBJECTIVES: Patients with CKD are more likely than others to have abnormalities in serum potassium (K(+)). Aside from severe hyperkalemia, the clinical significance of K(+) abnormalities is not known. We sought to examine the association of serum K(+) with mortality and hospitalization rates within narrow eGFR strata to understand how the burden of hyperkalemia varies by CKD severity. Associations were examined between serum K(+) and discontinuation of medications that block the renin-angiotensin-aldosterone system (RAAS), which are known to increase serum K(+). DESIGN, SETTING, PARTICIPANTS, pooled adjusted incidence rate ratios were 3.05 (95% confidence interval, 2.53 to 3.68) and 3.31 (95% confidence interval, 2.52 to 4.34) for K(+) levels <3.5 mEq/L and ≥6.0 mEq/L, respectively. Within eGFR strata, there were U-shaped associations of serum K(+) with rates of MACE, hospitalization, and discontinuation of RAAS blockers. CONCLUSIONS: Both hyperkalemia and hypokalemia were independently associated with higher rates of death, MACE, hospitalization, and discontinuation of RAAS blockers in patients with CKD who were not undergoing dialysis. Future studies are needed to determine whether interventions targeted at maintaining normal serum K(+) improve outcomes in this population.

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