Racial and Ethnic Differences in Mortality Associated with Serum Potassium in Incident Peritoneal Dialysis Patients.
ABSTRACT: BACKGROUND:Abnormalities in serum potassium are risk factors for sudden cardiac death and arrhythmias among dialysis patients. Although a previous study in hemodialysis patients has shown that race/ethnicity may impact the relationship between serum potassium and mortality, the relationship remains unclear among peritoneal dialysis (PD) patients where the dynamics of serum potassium is more stable. METHODS:Among 17,664 patients who started PD between January 1, 2007 and December 31, 2011 in a large US dialysis organization, we evaluated the association of serum potassium levels with all-cause and arrhythmia-related deaths across race/ethnicity using time-dependent Cox models with adjustments for demographics. We also used restricted cubic spline functions for serum potassium levels to explore non-linear associations. RESULTS:Baseline serum potassium levels were the highest among Hispanics (4.2 ± 0.7 mEq/L) and lowest among non-Hispanic blacks (4.0 ± 0.7 mEq/L). Among 2,949 deaths during the follow-up of median 2.2 (interquartile ranges 1.3-3.2) years, 683 (23%) were arrhythmia-related deaths. Overall, both hyperkalemia and hypokalemia (i.e., serum potassium levels >5.0 and <3.5 mEq/L, respectively) were associated with higher all-cause and arrhythmia-related mortality. In a stratified analysis according to race/ethnicity, the association of hypokalemia with all-cause and arrhythmia-related mortality was consistent with an attenuation for arrhythmia-related mortality in non-Hispanic blacks. Hyperkalemia was associated with all-cause and arrhythmia-related mortality in non-Hispanic whites and non-Hispanic blacks, but no association was observed in Hispanics. CONCLUSION:Among incident PD patients, hypokalemia was consistently associated with all-cause and arrhythmia-related deaths irrespective of race/ethnicity. However, while hyperkalemia was associated with both death outcomes in non-Hispanic blacks and whites, it was not associated with either death outcome in Hispanic patients. Further studies are needed to demonstrate whether different strategies should be followed for the management of serum potassium levels according to race/ethnicity.
Project description:Hyperkalemia is observed in chronic kidney disease patients and may be a risk factor for life-threatening arrhythmias and death. Race/ethnicity may be important modifiers of the potassium-mortality relationship in maintenance hemodialysis (MHD) patients given that potassium intake and excretion vary among minorities.We examined racial/ethnic differences in baseline serum potassium levels and all-cause and cardiovascular mortality using Cox proportional hazard models and restricted cubic splines in a cohort of 102,241 incident MHD patients. Serum potassium was categorized into 6 groups: ?3.6, >3.6 to ?4.0, >4.0 to ?4.5 (reference), >4.5 to ?5.0, >5.0 to ?5.5, and >5.5 mEq/L. Models were adjusted for case-mix and malnutrition-inflammation cachexia syndrome (MICS) covariates.The cohort was composed of 50% whites, 34% African-Americans, and 16% Hispanics. Hispanics tended to have the highest baseline serum potassium levels (mean ± SD: 4.58 ± 0.55 mEq/L). Patients in our cohort were followed for a median of 1.3 years (interquartile range 0.6-2.5). In our cohort, associations between higher potassium (>5.5 mEq/L) and higher mortality risk were observed in African-American and whites, but not Hispanic patients in models adjusted for case-mix and MICS covariates. While in Hispanics only, lower serum potassium (<3.6 mEq/L) levels were associated with higher mortality risk. Similar trends were observed for cardiovascular mortality.Higher potassium levels were associated with higher mortality risk in white and African-American MHD patients, whereas lower potassium levels were associated with higher death risk in Hispanics. Further studies are needed to determine the underlying mechanisms for the differential association between potassium and mortality across race/ethnicity.
Project description:Patients with chronic kidney disease (CKD) have a high risk of hyperkalemia, which increases mortality and can lead to renin-angiotensin-aldosterone system inhibitor (RAASi) dose reduction or discontinuation. Patiromer, a nonabsorbed potassium binder, has been shown to normalize serum potassium in patients with CKD and hyperkalemia on RAASi. Here, patiromer's onset of action was determined in patients with CKD and hyperkalemia taking at least one RAASi. After a 3-day potassium- and sodium-restricted diet in an inpatient research unit, those with sustained hyperkalemia (serum potassium 5.5 - under 6.5?mEq/l) received patiromer 8.4?g/dose with morning and evening meals for a total of four doses. Serum potassium was assessed at baseline (0?h), 4?h postdose, then every 2-4?h to 48?h, at 58?h, and during outpatient follow-up. Mean baseline serum potassium was 5.93?mEq/l and was significantly reduced by 7?h after the first dose and at all subsequent times through 48?h. Significantly, mean serum potassium under 5.5?mEq/l was achieved within 20?h. At 48?h (14?h after last dose), there was a significant mean reduction of 0.75?mEq/l. Serum potassium did not increase before the next dose or for 24?h after the last dose. Patiromer was well tolerated, without serious adverse events and no withdrawals. The most common gastrointestinal adverse event was mild constipation in two patients. No hypokalemia (serum potassium under 3.5?mEq/l) was observed. Thus, patiromer induced an early and sustained reduction in serum potassium and was well tolerated in patients with CKD and sustained hyperkalemia on RAASis.
Project description:Chronic kidney disease (CKD) patients have increased risks of sudden cardiac arrest and sudden cardiac death (SCA/SCD) that are not explained by traditional risk factors. We examined associations between serum potassium and SCA/SCD in a large cohort of patients with coronary artery disease (CAD) and moderate CKD.Among 22,009 patients who underwent cardiac catheterization at our institution between 1999 and 2011, 6181 patients had an estimated glomerular filtration rate of ?60 ml/min per 1.73 m2 and were not receiving renal replacement therapy. The risk of SCA/SCD and all-cause mortality associated with potassium concentration was evaluated at the time of cardiac catheterization (baseline) and most proximate to SCA/SCD events. Covariate-adjusted Cox models were used to examine relationships between baseline potassium measurements and outcomes. A propensity score-matched, case-control design was used to assess risk associations of potassium measurements obtained proximate to SCA events.In the baseline potassium analysis, compared with levels in the normal range, there was no significant risk association between hyperkalemia (>5 mEq/l) or hypokalemia (<3.5 mEq/l) and SCA/SCD or all-cause death after covariate adjustment. In the proximate potassium analysis, hyperkalemia occurred more frequently than hypokalemia (16.7% vs. 3%), and was associated with a doubling in SCA/SCD risk (adjusted odd ratio: 2.37; 95% confidence interval: 1.33-4.23) whereas there was no significant relationship between hypokalemia and outcome.Among CKD patients with significant CAD, elevated serum potassium levels >5.0 mEq/l are common and are associated with an increased short-term risk of SCA/SCD. Early detection and treatment of hyperkalemia may reduce the high risk of SCD among CKD patients.
Project description:Hypokalemia is a common electrolyte disturbance and is related to poor prognosis in patients with cardiovascular disease. However, the role of hypokalemia in patients with vasospastic angina (VSA) has not yet been studied. The present study enrolled 1454 patients diagnosed with VSA according to ergonovine provocation test results and available admission serum potassium data. The primary outcome was a composite of cardiac death, acute coronary syndrome, and new-onset life-threatening arrhythmia. Based on a hypokalemia definition as serum potassium concentration???3.5 mEq/L, the hypokalaemia group included 70 patients (4.8%). The median potassium levels were 3.4 mEq/L [interquartile range (IQR) 3.3-3.5] in the hypokalemia group and 4.1 mEq/L (IQR 3.9-4.3) in the no-hypokalemia group. The median follow-up duration was 764 days. Primary outcomes occurred in seven patients (10.0%) in the hypokalemia group and 51 patients (3.7%) in the no-hypokalemia group. The Kaplan-Meier analysis showed a higher cumulative incidence of primary outcomes in the hypokalemia group compared to that in the no-hypokalemia group (log-rank P?=?0.014). Multivariate Cox regression analysis also showed that hypokalemia was an independent predictor of primary outcomes. In conclusion, hypokalemia at admission was associated with adverse clinical outcomes in VSA.
Project description:Background Hyperkalemia has been associated with increased mortality in patients with myocardial infarction, but few data exist regarding hyperkalemia in cardiac intensive care unit ( CICU ) patients. We hypothesize that hyperkalemia is associated with increased mortality in unselected CICU patients. Methods and Results We retrospectively reviewed a historical cohort of 9681 CICU patients admitted from January 2007 to December 2015. Hyperkalemia was defined as admission potassium ≥5.0 mEq/L and hypokalemia as admission potassium <3.5 mEq/L. Multivariate logistic regression was used to determine predictors of in-hospital mortality. Postdischarge survival was assessed using Kaplan-Meier analysis and Cox proportional hazards models. The mean age of included patients was 67±15 years, with 36% females, and in-hospital mortality was 9%. Hyperkalemia occurred in 1187 (12.3%) and hypokalemia occurred in 719 (7.4%) patients. Both patients with hyperkalemia (unadjusted odds ratio, 2.85; 95% CI, 2.40-3.39; P<0.001) and patients with hypokalemia (unadjusted odds ratio, 2.31; 95% CI, 1.85-2.88; P<0.001) were at increased risk of unadjusted in-hospital mortality. After adjustment for illness severity and renal function, only patients with hyperkalemia demonstrated increased risk of in-hospital death (adjusted odds ratio, 1.44; 95% CI, 1.11-1.87; P=0.006). Among hospital survivors, only patients with hyperkalemia had lower postdischarge survival by Kaplan-Meier analysis ( P<0.001). After adjustment for illness severity and renal function, hospital survivors with admission hyperkalemia remained at increased risk for postdischarge mortality (adjusted hazard ratio, 1.20; 95% CI, 1.08-1.34; P<0.001). Conclusions Hyperkalemia on CICU admission is associated with higher in-hospital and postdischarge mortality, independent of renal function and illness severity. These findings emphasize the importance of potassium abnormalities as a risk predictor in patients admitted to the CICU .
Project description:BACKGROUND: In the chronic kidney disease (CKD) population, the impact of serum potassium (sK) on renal outcomes has been controversial. Moreover, the reasons for the potential prognostic value of hypokalemia have not been elucidated. DESIGN PARTICIPANTS & MEASUREMENTS: 2500 participants with CKD stage 1-4 in the Integrated CKD care program Kaohsiung for delaying Dialysis (ICKD) prospective observational study were analyzed and followed up for 2.7 years. Generalized additive model was fitted to determine the cutpoints and the U-shape association between sK and end-stage renal disease (ESRD). sK was classified into five groups with the cutpoints of 3.5, 4, 4.5 and 5 mEq/L. Cox proportional hazard regression models predicting the outcomes were used. RESULTS: The mean age was 62.4 years, mean sK level was 4.2±0.5 mEq/L and average eGFR was 40.6 ml/min per 1.73 m(2). Female vs male, diuretic use vs. non-use, hypertension, higher eGFR, bicarbonate, CRP and hemoglobin levels significantly correlated with hypokalemia. In patients with lower sK, nephrotic range proteinuria, and hypoalbuminemia were more prevalent but the use of RAS (renin-angiotensin system) inhibitors was less frequent. Hypokalemia was significantly associated with ESRD with hazard ratios (HRs) of 1.82 (95% CI, 1.03-3.22) in sK <3.5mEq/L and 1.67 (95% CI,1.19-2.35) in sK?=?3.5-4 mEq/L, respectively, compared with sK?=?4.5-5 mEq/L. Hyperkalemia defined as sK >5 mEq/L conferred 1.6-fold (95% CI,1.09-2.34) increased risk of ESRD compared with sK?=?4.5-5 mEq/L. Hypokalemia was also associated with rapid decline of renal function defined as eGFR slope below 20% of the distribution range. CONCLUSION: In conclusion, both hypokalemia and hyperkalemia are associated with increased risk of ESRD in CKD population. Hypokalemia is related to increased use of diuretics, decreased use of RAS blockade and malnutrition, all of which may impose additive deleterious effects on renal outcomes.
Project description:Hypokalemia and hyperkalemia are often noted in chronic kidney disease (CKD) patients, but their impact on mortality and end-stage renal disease (ESRD) is less well understood. We aimed at studying the associations between potassium disorders, and mortality and progression to ESRD in a CKD population.Using our electronic health record-based CKD registry, 36,359 patients with eGFR <60 ml/min/1.73 m(2) and potassium levels measured from January 1, 2005 to September 15, 2009 were identified. We examined factors associated with hypokalemia (<3.5 mmol/l) and hyperkalemia (>5.0 mmol/l) using logistic regression models and associations between serum potassium levels (both as continuous and categorical variables) and all-cause mortality or ESRD using Cox-proportional hazards models.Serum potassium <3.5 mmol/l was noted among 3% and >5.0 mmol/l among 11% of the study population. In the multivariable logistic regression analysis, lower eGFR, diabetes and use of ACE inhibitors or Angiotensin-Receptor Blockers were associated with higher odds of having hyperkalemia. Heart failure and African American race were factors associated with higher odds of hypokalemia. After adjustment for covariates including kidney function, serum potassium <4.0 and >5.0 mmol/l were significantly associated with increased mortality risk, but there was no increased risk for progression to ESRD. Time-dependent repeated measures analysis confirmed these findings. When potassium was examined as a continuous variable, there was a U-shaped association between serum potassium levels and mortality.In patients with stage 3-4 CKD, serum potassium levels <4.0 and >5.0 mmol/l are associated with higher mortality but not with ESRD.
Project description:<h4>Background</h4>The relationship between serum potassium, mortality, and conditions commonly associated with dyskalemias, such as heart failure (HF), chronic kidney disease (CKD), and/or diabetes mellitus (DM) is largely unknown.<h4>Methods</h4>We reviewed electronic medical record data from a geographically diverse population (n = 911,698) receiving medical care, determined the distribution of serum potassium, and the relationship between an index potassium value and mortality over an 18-month period in those with and without HF, CKD, and/or DM. We examined the association between all-cause mortality and potassium using a cubic spline regression analysis in the total population, a control group, and in HF, CKD, DM, and a combined cohort.<h4>Results</h4>27.6% had a potassium <4.0 mEq/L, and 5.7% had a value ?5.0 mEq/L. A U-shaped association was noted between serum potassium and mortality in all groups, with lowest all-cause mortality in controls with potassium values between 4.0 and <5.0 mEq/L. All-cause mortality rates per index potassium between 2.5 and 8.0 mEq/L were consistently greater with HF 22%, CKD 16.6%, and DM 6.6% vs. controls 1.2%, and highest in the combined cohort 29.7%. Higher mortality rates were noted in those aged ?65 vs. 50-64 years. In an adjusted model, all-cause mortality was significantly elevated for every 0.1 mEq/L change in potassium <4.0 mEq/L and ?5.0 mEq/L. Diuretics and renin-angiotensin-aldosterone system inhibitors were related to hypokalemia and hyperkalemia respectively.<h4>Conclusion</h4>Mortality risk progressively increased with dyskalemia and was differentially greater in those with HF, CKD, or DM.
Project description:OBJECTIVES:Our objectives were (1) to characterize the distribution of serum potassium levels at ICU admission, (2) to examine the relationship between dyskalemia at ICU admission and occurrence of cardiac events, and (3) to study both the association between dyskalemia at ICU admission and dyskalemia correction by day 2 on 28-day mortality. DESIGN:Inception cohort study from the longitudinal prospective French multicenter OUTCOMEREA database (1999-2014) SETTING: 22 French OUTCOMEREA network ICUs PATIENTS: Patients were classified into six groups according to their serum potassium level at admission: three groups of hypokalemia and three groups of hyperkalemia defined as serious hypokalemia [K+] <?2.5 and serious hyperkalemia [K+] >?7?mmol/L, moderate hypokalemia 2.5???[K+]?<?3?mmol/L and moderate hyperkalemia 6?<?[K+]???7?mmol/L, and mild hypokalemia 3???[K+] <?3.5?mmol/L and mild hyperkalemia 5?<?[K+] ??6?mmol/L. We sorted evolution at day 2 of dyskalemia into three categories: balanced, not-balanced, and overbalanced. INTERVENTION:None MEASUREMENTS AND MAIN RESULTS: Of 12,090 patients, 2108 (17.4%) had hypokalemia and 1445 (12%) had hyperkalemia. Prognostic impact of dyskalemia and its correction was assessed using multivariate Cox models. After adjustment, hypokalemia and hyperkalemia were independently associated with a greater risk of 28-day mortality. Mild hyperkalemic patients had the highest mortality (hazard ratio (HR) 1.29, 95% confidence interval (CI) [1.13-1.47], p?<?0.001). Adjusted 28-day mortality was higher if serum potassium level was not-balanced at day 2 (aHR?=?1.51, 95% CI [1.30-1.76], p?<?0.0001) and numerically higher but not significantly different if serum potassium level was overbalanced at day 2 (aHR?=?1.157, 95% CI [0.84-1.60], p?=?0.38). Occurrence of cardiac events was evaluated by logistic regression. Except for patients with serious hypokalemia at admission, the depth of dyskalemia was associated with increased risk of cardiac events. CONCLUSIONS:Dyskalemia is common at ICU admission and associated with increased mortality. Occurrence of cardiac events increased with dyskalemia depth. A correction of serum potassium level by day 2 was associated with improved prognosis.
Project description:BACKGROUND:Although hypokalemia has been viewed as a significant concern among patients with heart failure (HF), recent advances in HF management tend to increase the risk of hyperkalemia. OBJECTIVE:To characterize contemporary data regarding correlates and prognostic values of dyskalemia in patients with HF. DESIGN, SETTING, AND PARTICIPANTS:In cross-sectional and longitudinal analyses, we studied 142,087 patients with newly diagnosed HF in US nationwide Veterans Administration database from 2005 through 2013. EXPOSURES:Demographic characteristics, laboratory variables, comorbidities, and medication use for the analysis of correlates of dyskalemia as well as potassium level in the analysis of mortality. MAIN OUTCOMES AND MEASURES:Dyskalemia and mortality. RESULTS:Hypokalemia (<3.5 mmol/L) at baseline was observed in 3.0% of the population, whereas hyperkalemia (?5.5 mmol/L) was seen in 0.9%. An additional 20.4% and 5.7% had mild hypokalemia (3.5-3.9 mmol/L) and mild hyperkalemia (5.0-5.4 mmol/L). Key correlates were black race, higher blood pressure, and use of potassium-wasting diuretics for hypokalemia, and lower kidney function for hyperkalemia. Baseline potassium levels showed a U-shaped association with mortality, with the lowest risk between 4.0-4.5 mmol/L. With respect to potassium levels over a year after HF diagnosis, persistent (>50% of measurements), intermittent (>1 occurrence but ?50%), and transient (1 occurrence) hypo- and hyperkalemia were also related to increased mortality in a graded fashion regardless of the aforementioned thresholds for dyskalemia. These dyskalemic patterns were also related to other clinical actions and demands such as emergency room visit. CONCLUSIONS:Potassium levels below 4 mmol/L and above 5 mmol/L at and after HF diagnosis were associated with poor prognosis and the clinical actions. HF patients (particularly with risk factors for dyskalemia like black race and kidney dysfunction) may require special attention for both hypo- and hyperkalemia.