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

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, & measurements A cohort of patients with CKD (eGFR,60 ml/min per 1.73 m 2 ) with serum K + data were studied (n=55,266) between January 1, 2009, and June 30, 2013 (study end). Serum K + , eGFR, and covariates were considered on a time-updated basis. Mortality, major adverse cardiovascular events (MACE), hospitalization, and discontinuation of RAAS blockers were considered per time at risk.Results During the study, serum K + levels of 5.5-5.9 and $6.0 mEq/L were most prevalent at lower eGFR: they were present, respectively, in 1.7% and 0.2% of patient-time for eGFR of 50-59 ml/min per 1.73 m 2 versus 7.6% and 1.8% of patient-time for eGFR,30 ml/min per 1.73 m 2 . Serum K + level ,3.5 mEq/L was present in 1.2%-1.4% of patient-time across eGFR strata. The median follow-up time was 2.76 years. There was a U-shaped association between serum K + and mortality; 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.

Inflammation: A Key Contributor to the Genesis and Progression of Chronic Kidney Disease

“…Similarly, Hayes et al [40] evaluated a cohort of pre-dialysis CKD male patients ( n = 1,227) and found that serum K + of <3.6 mEq/L was associated with faster CKD progression compared to serum K + of 3.6-5.5 mEq/L. Several other studies demonstrated a significant association of serum K + <4.0 mEq/L and mortality, but the index of inflammation and follow up on CKD progression were not evaluated in sufficient detail [41][42][43] . Collectively, consistent with prior studies in animal CKD models [44] and known information of hypokalemia being a stimulator for ammonium genesis, angiotensin II, inflammatory mediators, and oxidative stress [28,45] , even mild degrees of hypokalemia, 3.5-4.0 mEq/L (which may be considered "normal") in patients with CKD can induce inflammation and poor clinical outcomes.…”

Frequency of Hyperkalemia in Chronıc Kidney Patients Under Regular Nephrology Care

“…The 1-day-mortality ratio was increased significantly in hospitalized patients with serum K levels above 5.5 mEq/L [17]. In a retrospective study with non-dialyzed CKD patients, when patients were followed for an average of 2.76 years, both hypokalemia and hyperkalemia were found to have a strong, independent, and statistically significant association with mortality, major cardiovascular events, and increased incidence of hospitalization [23].…”

“…There is a U-shaped relationship between serum K level and mortality, both low and high serum K values are associated with mortality [16,23,24]. Significant associations were found between hyperkalemia and increased risk of mortality and arrhythmia in observational studies [17,23,24].…”

“…Significant associations were found between hyperkalemia and increased risk of mortality and arrhythmia in observational studies [17,23,24]. The risk of ventricular fibrillation is increased in patients with a serum K level above 5.0 mEq/L and hospitalized with an acute coronary event [24].…”

Should We STOP Angiotensin Converting Enzyme Inhibitors/Angiotensin Receptor Blockers in Advanced Kidney Disease?

“…The adjusted mortality for patients with a serum potassium >6 mmol/l was 3.08 (2.17-4.37), MACE 2.11 (1.68-2.65) and discontinuation of RAS blockade 1.81 (1.45-2.26) in comparison to patients with potassium <6 mmol/l [82]. …”