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Serum Potassium and Risk of Death or Kidney Replacement Therapy in Older People With CKD Stages 4-5: Eight-Year
Esther N M de Rooij1, Johan W de Fijter2, Saskia Le Cessie3
1Department of Nephrology, Leiden University Medical Center, Leiden; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden.
Insights
Both low and high serum potassium levels increase the risk of death or kidney replacement therapy (KRT) in older adults with advanced chronic kidney disease (CKD). The lowest risk was observed at 4.9 mmol/L, highlighting the importance of managing both hypo- and hyperkalemia.
Area of Science:
- Nephrology
- Cardiology
- Geriatrics
Background:
- Hypokalemia can accelerate kidney function decline and both hypo- and hyperkalemia pose risks for sudden cardiac death.
- The relationship between serum potassium levels and mortality or the need for kidney replacement therapy (KRT) in advanced chronic kidney disease (CKD) is not well understood.
- Older individuals with CKD stage 4-5 are particularly vulnerable to potassium-related complications.
Purpose of the Study:
- To investigate the association between serum potassium levels and the combined outcome of death or initiation of KRT in older patients with advanced CKD.
- To identify the optimal serum potassium range associated with the lowest risk of adverse outcomes in this population.
Main Methods:
- A prospective observational cohort study of 1,714 patients (≥65 years) with estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73m² from the European Quality (EQUAL) study.
- Serum potassium was measured every 3-6 months and categorized into multiple levels.
- Cox proportional hazards and restricted cubic spline analyses were used to examine the association with death or KRT, adjusting for relevant covariates.
Main Results:
- Over 8 years, 24% of patients died before KRT and 35% started KRT.
- A U-shaped relationship was observed between serum potassium and the risk of death or KRT.
- The adjusted hazard ratios indicated increased risk at both low (≤3.5 mmol/L) and high (>5.5 mmol/L) potassium levels, with the lowest risk at approximately 4.9 mmol/L.
Conclusions:
- Serum potassium levels outside the range of approximately 4.9 mmol/L are associated with an increased risk of death or the need for KRT in older patients with advanced CKD.
- These findings emphasize the critical importance of maintaining serum potassium within a specific range, addressing both hypokalemia and hyperkalemia, in this vulnerable patient group.
- Clinical management strategies for advanced CKD should consider the dual risk posed by abnormal potassium levels.
Rationale & Objective:
Hypokalemia may accelerate kidney function decline. Both hypo- and hyperkalemia can cause sudden cardiac death. However, little is known about the relationship between serum potassium and death or the occurrence of kidney failure requiring replacement therapy (KRT). We investigated this relationship in older people with chronic kidney disease (CKD) stage 4-5.
Study Design:
Prospective observational cohort study.
Setting & Participants:
We followed 1,714 patients (≥65 years old) from the European Quality (EQUAL) study for 8 years from their first estimated glomerular filtration rate (eGFR)<20mL/min/1.73m2 measurement.
Exposure:
Serum potassium was measured every 3 to 6 months and categorized as≤3.5,>3.5-≤4.0,>4.0-≤4.5,>4.5-≤5.0 (reference),>5.0-≤5.5, >5.5-≤6.0, and>6.0mmol/L.
Outcome:
The combined outcome death before KRT or start of KRT.
Analytical Approach:
The association between categorical and continuous time-varying potassium and death or KRT start was examined using Cox proportional hazards and restricted cubic spline analyses, adjusted for age, sex, diabetes, cardiovascular disease, renin-angiotensin-aldosterone system (RAAS) inhibition, eGFR, and subjective global assessment (SGA).
Results:
At baseline, 66% of participants were men, 42% had diabetes, 47% cardiovascular disease, and 54% used RAAS inhibitors. Their mean age was 76±7 (SD) years, mean eGFR was 17±5 (SD) mL/min/1.73m2, and mean SGA was 6.0±1.0 (SD). Over 8 years, 414 (24%) died before starting KRT, and 595 (35%) started KRT. Adjusted hazard ratios for death or KRT according to the potassium categories were 1.6 (95% CI, 1.1-2.3), 1.4 (95% CI, 1.1-1.7), 1.1 (95% CI, 1.0-1.4), 1 (reference), 1.1 (95% CI, 0.9-1.4), 1.8 (95% CI, 1.4-2.3), and 2.2 (95% CI, 1.5-3.3). Hazard ratios were lowest at a potassium of about 4.9mmol/L.
Limitations:
Shorter intervals between potassium measurements would have allowed for more precise estimations.
Conclusions:
We observed a U-shaped relationship between serum potassium and death or KRT start among patients with incident CKD 4-5, with a nadir risk at a potassium level of 4.9mmol/L. These findings underscore the potential importance of preventing both high and low potassium in patients with CKD 4-5.
Plain-Language Summary:
Abnormal potassium blood levels may increase the risk of death or kidney function decline, especially in older people with chronic kidney disease (CKD). We studied 1,714 patients aged≥65 years with advanced CKD from the European Quality (EQUAL) study and followed them for 8 years. We found that both low and high levels of potassium were associated with an increased risk of death or start of kidney replacement therapy, with the lowest risk observed at a potassium level of 4.9 mmol/L. In patients with CKD, the focus is often on preventing high blood potassium. However, this relatively high optimum potassium level stresses the potential importance of also preventing low potassium levels in older patients with advanced CKD.
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