Serum potassium disturbances are common among individuals with chronic kidney disease (CKD) stages 4-5. Patients may experience hyperkalemia due to impaired urinary potassium excretion and the use of renin-angiotensin-aldosterone system (RAAS) inhibitors for cardiorenoprotection, or they may experience hypokalemia due to treatment with nonpotassium-sparing diuretics or malnourishment.
Both hyperkalemia and hypokalemia are associated with muscle paralysis and potentially fatal cardiac arrhythmias. Further, there is an association between hypokalemia and increased rate of decline in kidney function in those with CKD, likely via chronic interstitial nephritis and fibrosis (hypokalemic nephropathy).
Serum potassium disturbances may be related to progression to kidney failure requiring kidney replacement therapy (KRT) and mortality. Older patients with CKD stages 4-5 are at high risk of kidney failure and mortality. The relationship between potassium level and the combined outcome of death or KRT may differ in older patients compared with younger individuals.
According to Esther N. M de Rooij, MD, and colleagues, there are few data available on the relationship between serum potassium and death or the occurrence of kidney failure requiring KRT in older people with CKD stage 4-5. The researchers conducted a prospective observational cohort study designed to examine that relationship in patients ≥65 years of age with CKD stage 4-5. Results were reported in the American Journal of Kidney Diseases.
The study exposure was serum potassium measured every 3 to 6 months and categorized according to seven prespecified categories: ≤3.5, >3.5 to ≤4.0, >4.0 to ≤4.5, >4.5 to ≤5.0, >5.0 to ≤5.5, >5.5 to ≤6.0, and >6.0 mmol/L. The outcome of interest was the combined outcome of death before KRT or initiation of KRT.
Cox proportional hazards and restricted cubic spine analyses were used to assess the association between categorical and continuous time-varying potassium and death or KRT. The analyses were adjusted for age, sex, diabetes, cardiovascular disease, RAAS inhibition, estimated glomerular filtration rate (eGFR), and subjective global assessment (SGA).
Data from the European Quality (EQUAL) study were utilized for the current study. Patients ≥65 years of age were followed for 8 years from their first eGFR <20 mL/min/1.73 m2 measurement.
Of the 1736 EQUAL study participants, 1714 met eligibility requirements (at least one available serum potassium measurement). At baseline, mean age was 76 years, 66% were men, 42% had diabetes, 47% had cardiovascular disease, and 54% used RAAS inhibitors. Mean eGFR was 17 mL/min/1.73 m2, mean SGA was 6.0, and mean serum potassium level was 4.6 mmol/L.
Distribution of potassium levels in the seven potassium categories was as follows: 2%, 13%, 28%, 33%, 17%, 5%, and 2%, respectively. In the lowest category (≤3.5 mmol/L), the mean value was 3.3 mmol/L, and in the highest category (>6.0 mmol/L) the mean value was 6.3 mmol/L. Compared with the reference category (>4.5 to ≤5.0 mmol/L), patients in the lowest potassium category had lower SGA scores, more often had diabetes, and less often had cardiovascular disease. Patients in the highest serum potassium category were more often men, had a lower eGFR, and less often had cardiovascular disease.
During follow-up, 6091 potassium measurements were performed (average, 3.6 measurements per participant). The distribution of serum potassium during follow-up was similar to the distribution at baseline. Of the total cohort, 7% (n=126) experienced serum potassium ≤3.5 mmol/L, and 13% (n=230) and 3% (n=59) experienced serum potassium >5.5 to ≤6.0 mmol/L and >6.0 mmol/L during follow-up, respectively. Compared with normal serum potassium levels, the low or high levels were less often persistent for two or more consecutive visits.
Median time to death or initiation of KRT was 2.6 years. Twenty-four percent of participants died (n=414), 1% (n=15) had a preemptive kidney transplantation, and 34% (n=580) initiated dialysis during 3851 person-years, yielding an overall crude combined death or KRT start rate of 26.2 (95% CI, 24.6-27.8) per 100 patient-years. Among older patients with an eGFR <20 mL/min/1.73 m2, KRT initiation was more common than death before KRT. Of the 414 deaths before start of KRT, 26% (n=109) were due to cardiovascular disease.
In the lowest serum potassium category of ≤3.5 mmol/L, the absolute rates of combined death or initiation of KRT were 40 (95% CI, 28-54) per 100 person-years. The rates were 22 (95% CI, 20-24) per 100 person-years in the reference category (>4.5 to ≤5.0 mmol/L), and 59 (95% CI, 40-85) per 100 person-years in the highest serum potassium category (>6.0 mmol/L).
Adjusted hazard ratios for death or initiation of KRT according to the serum 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), 1.0 (reference), 1.1 (95% CI, 0.9-1.4), 1.8 (95% CI, 1.4-2.3), and 2.2 (95% CI, 1.50-3.3). Hazard ratios were lowest at a potassium level of approximately 4.9 mmol/L.
The researchers cited some limitations to the study findings, including missing data, the inability to adjust for time-dependent confounding due to limited follow-up data on confounders, only updating serum potassium as a time-dependent variable, and using all-cause mortality rather than sudden cardiac death as the primary outcome.
“In conclusion,” the authors said, “We found a U-shaped relationship between serum potassium and the combined outcome of death or KRT start in patients aged ≥65 years with an incident eGFR <20 mL/min/1.73 m2 during 8 years of follow-up. Our results indicate a serum potassium level of approximately 4.9 mmol/L to be associated with the lowest hazard of death or KRT start. Compared with this optimum level, low (≤3.5 mmol/L) and high (>6.0 mmol/L) serum potassium concentrations were a 1.6- and 2.2-fold stronger hazard for death or KRT start after multivariable adjustment, respectively. This relatively high level may stress the importance of preventing both high and low serum potassium in older patients with CKD stages 4-5.”
Takeaway Points
- In older adults with chronic kidney disease stages 4-5, both hypokalemia and hyperkalemia may increase the risk of death or decline in kidney function leading to the need for kidney replacement therapy (KRT).
- Results of a prospective observational cohort study demonstrated a U-shaped relationship between serum potassium and death or initiation of KRT.
- A serum potassium level of approximately 4.9 mmol/L was associated with the lowest hazard of death or KRT start.
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