Racial and Ethnic Differences in Mortality Associated with Serum Potassium in a Large Hemodialysis Cohort.
ABSTRACT: 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:Unlike hemodialysis (HD), peritoneal dialysis (PD) is a continuous therapy and does not induce myocardial stunning. Yet, the death risk in HD and PD patients is similar. This study tested the hypothesis that serum potassium abnormalities contribute more to the death risk in PD patients than in HD patients.Data from patients treated in DaVita facilities between July 1, 2001 and June 30, 2006 (n=10,468 PD patients; n=111,651 HD patients) were used to determine association of serum potassium with mortality.PD patients were significantly more likely to have serum potassium < 4 mEq/L, with an adjusted odds ratio of 3.30 (95% confidence interval [95% CI], 3.05, 3.56). There was a U-shaped relationship between time-averaged serum potassium and all-cause and cardiovascular mortality of PD patients, with adjusted hazards ratios of 1.51 for all-cause mortality for potassium < 3.5 mEq/L (95% CI, 1.29, 1.76) and 1.52 for potassium ? 5.5 mEq/L (95% CI, 1.32, 1.75). The population-attributable risks for all-cause mortality for serum potassium < 4.0 and ? 5.5 mEq/L were 3.6% and 1.9%, respectively, in PD patients, and 0.8% and 1.5%, respectively, in HD patients.Abnormalities in serum potassium contribute disproportionately to the high death risk in PD patients. This may, in part, account for the equivalent cardiac risk seen with the two therapies.
Project description:BACKGROUND:Studies examining the association of dialysate potassium concentration and mortality in hemodialysis patients show conflicting findings. We hypothesized that low dialysate potassium concentrations are associated with higher mortality, particularly in patients with high pre-dialysis serum potassium concentrations. METHODS:We evaluated 624 hemodialysis patients from the prospective Malnutrition, Diet, and Racial Disparities in Kidney Disease study recruited from 16 outpatient dialysis facilities over 2011-2015 who underwent protocolized collection of dialysis treatment characteristics every 6 months. We examined the association of dialysate potassium concentration, categorized as 1, 2, and 3 mEq/L, with all-cause mortality risk in the -overall cohort, and stratified by pre-dialysis serum potassium (< 5 vs. ?5 mEq/L) using case-mix adjusted Cox models. RESULTS:In baseline analyses, dialysate potassium concentrations of 1 mEq/L were associated with higher mortality, whereas concentrations of 3 mEq/L were associated with similar mortality in the overall cohort (reference: 2 mEq/L): adjusted hazard ratios (aHRs; 95% CI) 1.70 (1.01-2.88) and 0.95 (0.64-1.39), respectively. In analyses stratified by serum potassium, baseline dialysate potassium concentrations of 1 mEq/L were associated with higher mortality in patients with serum potassium ?5 mEq/L but not in those with serum potassium < 5 mEq/L: aHRs (95% CI) 2.87 (1.51-5.46) and 0.74 (0.27-2.07), respectively (p interaction = 0.04). These findings were robust with incremental adjustment for serum potassium, potassium-binding resins, and potassium-modifying medications. CONCLUSION:Low (1 mEq/L) dialysate potassium -concentrations were associated with higher mortality, particularly in hemodialysis patients with high pre-dialysis serum potassium. Further studies are needed to identify therapeutic strategies that mitigate inter-dialytic serum potassium accumulation and subsequent high dialysate serum potassium gradients in this population.
Project description:Low serum potassium appears to be independently associated with incident type 2 diabetes, and low dietary potassium is more common in African Americans than in whites.We hypothesized that low serum potassium contributes to the excess risk of diabetes in African Americans.We analyzed data collected from 1987 to 1996 from the Atherosclerosis Risk in Communities (ARIC) Study. At baseline, we identified 2716 African American and 9493 white participants without diabetes. We used multivariate Cox models to estimate the relative hazards (RHs) of incident diabetes related to baseline serum potassium during 9 y of follow-up.Mean serum potassium concentrations were lower in African Americans than in whites at baseline (4.2 compared with 4.5 mEq/L; P < 0.01), and African Americans had a greater incidence of diabetes than did whites (26 compared with 13 cases/1000 person-years). The adjusted RHs (95% CI) of incident diabetes for those with serum potassium concentrations of <4.0, 4.0-4.4, and 4.5-4.9 mEq/L, compared with those with serum potassium concentrations of 5.0-5.5 mEq/L (referent), were 2.28 (1.21, 4.28), 1.97 (1.06, 3.65), and 1.85 (0.99, 3.47) for African Americans and 1.53 (1.14, 2.05), 1.49 (1.19, 1.87), and 1.27 (1.02, 1.58) for whites, respectively. Racial differences in serum potassium appeared to explain 18% of the excess risk of diabetes in African Americans, which is comparable with the percentage of risk explained by racial differences in body mass index (22%).Low serum potassium concentrations in African Americans may contribute to their excess risk of type 2 diabetes relative to whites. Whether interventions to increase serum potassium concentrations in African Americans might reduce their excess risk deserves further study. The ARIC Study is registered at clinicaltrials.gov as NCT00005131.
Project description: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:BACKGROUND:Atrial fibrillation (AF) occurs in approximately one in three patients after cardiac surgery, and is associated with increased short-term and long-term mortality, intensive care unit (ICU) and hospital stay, and increased cost of care. In an attempt to reduce AF incidence in these patients, serum potassium (K+) levels are commonly maintained at the high end of normal (4.5-5.5 mEq/L). However, such potassium supplementation is without proven benefit, and is not without negative consequences. It carries clinical risk, negatively impacts patient experience and is both time-consuming and costly. This protocol describes a randomised controlled pilot trial to assess the feasibility of a proposed randomised non-inferiority trial to investigate the impact of maintaining serum potassium ??3.6 mEq/L vs ??4.5 mEq/L on the incidence of new-onset atrial fibrillation in the first 120 hours after isolated elective coronary artery bypass grafting. METHODS:Design: this is a randomized feasibility trial as a pilot for a randomized non-inferiority trial. PARTICIPANTS:are 160 patients undergoing isolated coronary artery bypass grafting at two centres. Allocation: patients will be randomized (1:1) to protocols aiming to maintain serum potassium at either ??3.6 mEq/L ("relaxed control") or ??4.5 mEq/L ("tight control"). Primary analytic aim: was to assess the feasibility and acceptability of planning and delivering the intervention and trial methods to inform a full-scale non-inferiority trial. OUTCOME:the primary indicative efficacy outcome measures being field-tested are feasibility of participant recruitment and randomization, maintaining a protocol violation rate <?10%, and retaining 90% patient follow up 28 days after surgery. The primary clinical outcome measure of the future full "Tight K Study" will be incidence of AF after cardiac surgery. DISCUSSION:The Tight K Pilot will assess the feasibility of conducting the full trial, which is intended to confirm or refute the efficacy of current potassium management in preventing AF after cardiac surgery. TRIAL REGISTRATION:ClinicalTrials.gov, NCT03195647 . Registered on 23 May 2017. Last updated 19June 2017.
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:<h4>Aim</h4>Hyperkalemia increases the risk of sudden cardiac death (SCD) in hemodialysis patients. Our objective was to determine the association between administering low potassium dialysate to hyperkalemic hemodialysis patients and SCD.<h4>Methods</h4>We conducted a retrospective cohort study with patients undergoing maintenance hemodialysis from May 1, 2006, through December 31, 2013. The dialysate composition was adjusted over time according to monthly laboratory results. A 1.0 mEq/L potassium dialysate was applied in patients with predialysis hyperkalemia (>5.5 mEq/L) and was included as a time-dependent confounding factor. The clinical characteristics of enrolled patients, the incidence and timing of SCD and risk factors for all-cause mortality and SCD were analyzed.<h4>Results</h4>There were 312 patients on maintenance hemodialysis during the study period. One hundred and fifty-seven patients had been dialyzed against a 1.0 mEq/L potassium dialysate at least once. The rates of all-cause mortality and SCD were 48.17 and 20.74 per 1000 patient-years, respectively. A 1.12-fold increase in the risk of SCD in the 24-hour period starting with the hemodialysis procedure and a 1.36-fold increase in the 24 hours preceding a weekly cycle were found (p = 0.017). Multivariate Cox proportional hazards models showed that age, diabetes mellitus and predialysis hyperkalemia (>5.0 mEq/L) were significant predictors of all-cause mortality and SCD. Exposure to 1.0 mEq/L potassium dialysate, Kt/V, and serum albumin were independent protective factors against all-cause mortality. Only exposure to 1.0 mEq/L potassium dialysate significantly prevented SCD (hazard ratio = 0.33, 95% CI = 0.13-0.85).<h4>Conclusions</h4>Using low potassium dialysate in hyperkalemic hemodialysis patients may prevent SCD.
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:<h4>Aims</h4>At present, the clinical burden of hypokalaemia and hyperkalaemia among European heart failure patients, and relationships between serum potassium and adverse clinical outcomes in this population, is not well characterized. The aim of this study was to investigate associations between mortality, major adverse cardiac events, and renin-angiotensin-aldosterone system inhibitor (RAASi) discontinuation across serum potassium levels, in a UK cohort of incident heart failure patients.<h4>Methods and results</h4>This was a retrospective observational cohort study of newly diagnosed heart failure patients listed in the Clinical Practice Research Datalink, with a first record of heart failure (index date) between 2006 and 2015. Hypokalaemia and hyperkalaemia episodes were defined as the number of serum potassium measurements exceeding each threshold (<3.5, ?5.0, ?5.5, and ?6.0 mmol/L), without such a measurement in the preceding 7 days. Risk equations developed using Poisson generalized estimating equations were utilized to estimate adjusted incident rate ratios (IRRs) relating serum potassium and clinical outcomes (death, major adverse cardiac event, and RAASi discontinuation). Among 21,334 eligible heart failure patients, 1969 (9.2%), 7648 (35.9%), 2725 (12.8%), and 763 (3.6%) experienced episodes of serum potassium <3.5, ?5.0, ?5.5, and ?6.0 mmol/L, respectively. The adjusted IRRs for mortality exhibited a U-shaped association pattern with serum potassium. Relative to the reference category (4.5 to <5.0 mmol/L), adjusted IRRs for mortality were estimated as 1.98 (95% confidence interval: 1.69-2.33), 1.23 (1.12-1.36), 1.35 (1.14-1.60), and 3.02 (2.28-4.02), for patients with serum potassium <3.5, ?5.0 to <5.5, ?5.5 to <6.0, and ?6.0 mmol/L, respectively. The adjusted IRRs for major adverse cardiac events demonstrated a non-statistically significant relationship with serum potassium. Discontinuation of RAASi therapy exhibited a J-shaped trend in association with serum potassium. Compared with the reference category (4.5 to <5.0 mmol/L), adjusted IRRs were estimated as 1.07 (0.89-1.28) in patients with serum potassium <3.5 mmol/L, increasing to 1.32 (1.14-1.53) and 2.19 (1.63-2.95) among those with serum potassium ?5.5 to <6.0 and ?6.0 mmol/L, respectively.<h4>Conclusions</h4>In UK patients with new onset heart failure, both hypokalaemia and hyperkalaemia were associated with increased mortality risk, and hyperkalaemia was associated with increased likelihood of RAASi discontinuation. Our results demonstrate the potential importance of serum potassium monitoring for heart failure outcomes and management.
Project description:OBJECTIVE:To investigate the normal range of serum potassium, the prevalence of dyskalaemia and the associated factors in Chinese older adults. DESIGN:A cross-sectional study conducted from September 2017 to March 2018. SETTING:Forty-eight community elderly care facilities in four regions in northern China. PARTICIPANTS:A total of 1266 (308 apparently healthy and 958 unhealthy) participants 55 years or older and with fasting serum potassium measured. MAIN OUTCOME MEASURES AND METHODS:Serum potassium <3.5?mEq/L and >5.5?mEq/L (guidelines definition) and <2.5th and >97.5th percentiles of the distribution among healthy participants (our study definition) were both used to define hypokalaemia and hyperkalaemia, respectively. Multivariable generalised estimating equation models were used to adjust for clustering effect in the analyses of factors associated with risk of dyskalaemia and with variations in serum potassium. RESULTS:The study participants had a mean age of 70 (8.8) years. Among apparently healthy participants, the 2.5th and 97.5th percentiles of serum potassium distribution were 3.7 mEq/L and 5.3 mEq/L, respectively. Using the study definition, the prevalence of hyperkalaemia was 4.3% (95% CI 3.2% to 5.4%) and of hypokalaemia was 4.0% (95% CI 2.9% to 5.1%). Multivariable analyses showed that risk of hyperkalaemia was associated with unhealthy conditions (OR=2.21; 95%?CI 1.17 to 4.18); risk of hypokalaemia was associated with unhealthy conditions (OR=2.56; 95% CI 1.05 to 6.23), older age (OR=1.70 per 10-year increase; 95% CI 1.04 to 2.79) and region (OR=16.87; 95% CI 6.41 to 44.38); and higher serum potassium was associated with male gender (mean difference (MD)=0.12; 95%?CI 0.05 to 0.19) and estimated glomerular filtration rate <60?mL/min/1.73?m2 (MD=0.29; 95% CI 0.12 to 0.46). Using the guidelines definition, hyperkalaemia accounted for 2.7% (1.8%, 3.6%) and hypokalaemia 1.8% (1.1%, 2.5%). Analyses of the associated factors showed similar trends. CONCLUSIONS:The study suggested a narrower normal range of serum potassium for defining dyskalaemia, which was common in older Chinese and more prevalent in unhealthy ones. TRIAL REGISTRATION NUMBER:NCT03290716; Pre-results.