Baseline Serum Potassium Levels Research Articles

Efficacy and safety of patiromer for non-dialysis and dialysis patients with hyperkalemia: the randomized, placebo-controlled and long-term study.

The objectives of this phase two study are to investigate the efficacy of two starting doses of 8.4g and 16.8g and evaluate the long-term safety of patiromer in Japanese patients with hyperkalemia. This study comprised three cohorts; non-dialysis patients with baseline serum potassium (sK) level of 5.1 to < 6.0mmol/L (NDC1); 6.0 to < 6.5mmol/L (NDC2); dialysis patients with baseline sK level of 5.5 to < 6.5mmol/L (DC). The study design was one-week, randomized, double-blind, placebo-controlled, and open label extension for one year in NDC1, open label during the study in NDC2 and DC. Patients were randomly assigned to patiromer 8.4g, 16.8g or placebo in NDC1, 8.4g or 16.8g in NDC2 and DC. Dose was adjusted up to 25.2g according to the titration algorism in open label period. A total of 185 patients were randomized (NDC1:153, NDC2:10, and DC:22). The primary endpoint of the change in least squares mean sK levels at Week 1 in NDC1 was - 0.55, - 0.77 and - 0.10mmol/L for the 8.4g, 16.8g and placebo group (P < 0.001 for the patiromer group vs the placebo group). In all cohorts for each patiromer group, more than 80% of patients achieved normal sK at Week 5. There was no severe treatment-related adverse event. Treatment with patiromer was effective in lowering and maintaining target sK levels, also well tolerated for oneyear in Japanese patients with hyperkalemia.

Factors influencing the efficacy and safety of esaxerenone in hypertensive patients: a pooled analysis of five clinical studies on different comorbidities

This study aimed to identify factors associated with a strong home blood pressure (BP)-lowering effect of esaxerenone and the incidence of elevated serum potassium levels in hypertensive patients treated with esaxerenone. A pooled analysis of five multicenter, prospective, open-label single-arm studies was conducted, including 479 patients in the full analysis set (FAS) and 492 patients in the safety analysis set. Multivariate linear regression analysis of morning home systolic BP (SBP) and diastolic BP (DBP) changes from baseline to Week 12 in the FAS (primary endpoint) showed that male sex (estimated change 4.37 mmHg), office pulse rate ≥100 beats/min (25.10 mmHg), and calcium channel blocker (CCB) use as a basal antihypertensive agent (4.53 mmHg) were significantly associated with a positive estimated change (weaker BP-lowering effect) in morning home SBP. CCB use (3.70 mmHg) was associated with a positive estimated change in morning home DBP. Urine albumin‐to‐creatinine ratio 30 to <300 mg/gCr (−4.13 mmHg) was significantly associated with a negative estimated change (stronger BP-lowering effect) in morning home SBP. Based on multivariate logistic regression analysis, elevated baseline serum potassium level (≥4.5 vs < 4.5 mEq/L, odds ratio 13.502) was significantly associated with a high incidence of serum potassium level ≥5.5 mEq/L after esaxerenone treatment. In conclusion, factors associated with a strong BP-lowering effect of esaxerenone were female sex and use of renin–angiotensin system inhibitors as a basal antihypertensive drug. Patients with baseline serum potassium levels ≥4.5 mEq/L had an increased risk of developing elevated serum potassium levels (≥5.5 mEq/L) after esaxerenone treatment.

Increased Spironolactone Dosing in Acute Heart Failure Alters Potassium Homeostasis but Does not Enhance Decongestion

The ATHENA-HF (Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure) clinical trial found no improvements in natriuretic peptide levels or clinical congestion when spironolactone 100 mg/day for 96 hours was used in addition to usual treatment for acute heart failure. We performed a post hoc analysis of ATHENA-HF to determine whether spironolactone treatment induced any detectable pharmacodynamic effects and whether patients with potentially greater aldosterone activity experienced additional decongestion. Trial subjects previously treated with spironolactone were excluded. We first examined for changes in renal potassium handling. Using the baseline serum potassium level as a surrogate marker of spironolactone activity, we then divided each treatment arm into tertiles of baseline serum potassium and explored for differences in laboratory and clinical congestion outcomes. Among spironolactone-naïve patients, the change in serum potassium did not differ after 24 hours or 48 hours but was significantly greater with spironolactone treatment compared to placebo at 72 hours (0.23 ± 0.55 vs 0.03 ± 0.60 mEq/L; P = 0.042) and 96 hours (0.32 ± 0.51 vs 0.13 ± 0.72 mEq/L; P = 0.046). Potassium supplementation was similar at treatment start and at 24 hours, but spironolactone-treated patients required substantially less potassium replacement at 48 hours (24% vs 36%; P = 0.048), 72 hours (21% vs 37%; P = 0.013), and 96 hours (11% vs 38%; P < 0.001). When the treatment arms were divided into tertiles of baseline serum potassium, there were no differences in the 96-hour log N-terminal pro-B-type natriuretic peptide levels, net fluid loss, urine output, or dyspnea relief in any of the potassium groups, with no effect modification by treatment exposure. Spironolactone 100 mg/day for 96 hours in patients receiving intravenous loop diuresis for acute heart failure has no clear added decongestive ability but does meaningfully limit potassium wasting.

Vegetable and Fruit Intake Frequency and Mortality in Patients With and Without Chronic Kidney Disease: A Hospital-Based Cohort Study

Patients with advanced chronic kidney disease (CKD) are generally discouraged from consuming high amounts of vegetables and fruits given the potential risk of hyperkalemia. In the general population, however, lower vegetable and fruit intake is associated with higher mortality. This Japanese hospital-based prospective cohort study including non-CKD and CKD participants examined whether the frequency of vegetable and fruit intake is associated with mortality, and whether the presence of CKD modifies this association. Participants were 2,006 patients who visited the outpatient department of a general hospital between June 2008 and December 2016 (55% men; mean age, 69years). Among these participants, 902 (45%) and 131 (7%) were non-dialysis-dependent patients with CKD and hemodialysis patients, respectively. The frequency of vegetable and fruit intake was determined by a self-report questionnaire using an ordinal scale, "never or rarely," "sometimes," and "every day." Multivariable Cox proportional hazards analysis was conducted, adjusting for potential confounders. Vegetable and fruit intake frequency decreased with worsening CKD stage (P for trend < .001). Baseline serum potassium levels stratified by CKD stage were similar across the three vegetable and fruit intake frequency groups. During a median follow-up of 5.7years, 561 participants died (47.1/1,000 person-years). Adjusted hazard ratios relative to the "every day" group were 1.25 (95% confidence interval, 1.04-1.52) and 1.60 (95% confidence interval, 1.23-2.08) for the "sometimes" and "never or rarely" groups, respectively, after adjusting for demographic factors, comorbidities, and CKD status. When stratified by CKD status, a similar, albeit non-significant, dose-dependent relationship was observed between vegetable and fruit intake frequency and all-cause mortality irrespective of CKD status, with no effect modification by CKD status (Pinteraction=.69). A lower frequency of vegetable and fruit intake is significantly associated with a higher risk of death regardless of CKD status.

Effectiveness of sacubitril/valsartan for patients with cancer therapy‑related cardiac dysfunction: A systematic review of descriptive studies.

The present review assessed the effectiveness of sacubitril/valsartan in patients with cancer therapy-related cardiac dysfunction (CTRCD). Studies that included patients with CTRCD treated with sacubitril/valsartan were retrieved from the Medline, Embase, Cochrane Library and ClinicalTrials databases. Only descriptive studies on sacubitril/valsartan for patients with CTRCD were included in this review; therefore, all variables were qualitatively analyzed. A total of five studies comprising 109 patients were included. The duration from anticancer therapy to heart failure (HF) or from HF to the use of sacubitril/valsartan exhibited interindividual variations. In patients with CTRCD who were treated with sacubitril/valsartan, the left ventricular ejection fraction improved, N-terminal pro-B-type natriuretic peptide levels decreased and exercise tolerance improved, as indicated by the change in the New York Heart Association functional class. These clinical, echocardiographic and biochemical improvements were found for different dosages or treatment durations of sacubitril/valsartan. No difference was found between the baseline and follow-up serum creatinine and potassium levels. These findings, which are limited to descriptive studies, support the effectiveness of sacubitril/valsartan in improving heart function following CTRCD.

Incidence and Determinants of Piperacillin/Tazobactam-Associated Hypokalemia: A Retrospective Study.

Piperacillin/tazobactam (TZP) is a commonly used antibiotic for treating moderate-to-severe infections because of its broad-spectrum activity and recommendation as an alternative to carbapenem. TZP-associated severe hypokalemia has been consistently reported; however, related studies are very rare. This study aimed to evaluate the incidence and risk factors of TZP-associated hypokalemia (TAH). A retrospective cohort study was conducted on hospitalized adult patients who received TZP from 1 January 2015 to 31 December 2017 at a tertiary teaching hospital. Of the 713 patients, 13.9% had TAH. As a result of multivariate logistic regression analysis, older age (OR 1.03, 95% CI: 1.02–1.05, p < 0.001), female sex (OR 1.88, 95% CI: 1.18–3.00, p = 0.008), longer duration of TZP therapy (OR 1.08, 95% CI: 1.04–1.13, p < 0.001), and higher TZP daily dose (OR 1.10, 95% CI: 1.01–1.20, p = 0.049) were independently associated with TAH. In contrast, higher baseline serum potassium level (OR 0.13, 95% CI: 0.07–0.26, p < 0.001) was related to lower TAH. Furthermore, hypokalemia mostly occurred in the early days of TZP therapy (median onset time: 4 days). Thus, close monitoring of serum potassium levels, especially upon therapy initiation, is essential to prevent TAH.

Assessment of Patiromer Monotherapy for Hyperkalemia in an Acute Care Setting

Hyperkalemia is a common electrolyte disorder in hospitalized patients; however, the clinical usefulness of administering patiromer for reduction of serum potassium levels in this setting is unknown. To evaluate the outcomes associated with patiromer as monotherapy in patients with acute hyperkalemia in an acute care setting. This cohort study used electronic health record data from adult patients treated with patiromer for acute hyperkalemia in emergency departments, inpatient units, and intensive care units at an urban, academic medical center in the Bronx, New York, between January 30, 2018, and December 30, 2019. Data analysis was conducted between June 2020 and February 2021. A single dose of oral patiromer (8.4 g, 16.8 g, or 25.2 g). The primary outcome was the mean absolute reduction in serum potassium level from baseline at 3 distinct time intervals after patiromer administration: 0 to 6 hours, greater than 6 to 12 hours, and greater than 12 to 24 hours. Key secondary outcomes were the incidence of hypokalemia and potassium reduction stratified by baseline potassium level and care setting. Among 881 encounters of patiromer treatment, the mean (SD) age of patients was 67.4 (14.4) years; 463 encounters (52.6%) were for male patients, and most (338 [38.4%]) were for patients who identified as non-Hispanic Black. The mean (SD) baseline serum potassium level was 5.60 (0.35) mEq/L (to convert to mmol/L, multiply by 1.0), and within the first 6 hours after patiromer administration, the mean (SD) potassium reduction was 0.50 (0.56) mEq/L (P < .001). Both absolute and relative potassium reduction from baseline varied across baseline hyperkalemia severity but not by care setting. The lowest dose of patiromer (8.4 g) was used in 721 encounters (81.8%), and in 725 encounters (82.3%), no further doses of a potassium binder were required. Hypokalemia was noted in 2 encounters (0.2%) at 24 hours after patiromer administration. In this cohort study of patients with acute, non-life-threatening hyperkalemia, a single dose of patiromer was associated with a significant decrease in serum potassium levels and a low incidence of hypokalemia. These findings suggest that patiromer monotherapy may be useful in an institutional setting for managing elevated potassium levels and minimizing the risk of hypokalemia associated with other potassium control measures.

Effect of serum potassium level on renal function progression in stage Ⅲ-Ⅴ chronic kidney disease patients without dialysis

Objective: To investigate the effect of serum potassium level and hyperkalemia on the renal function decline in chronic kidney disease (CKD) patients. Methods: The clinical data at baseline and follow-up in stage Ⅲ-Ⅴ CKD patients without dialysis who were followed up for more than one year in Tianjin First Central Hospital from May 2015 to June 2019 and Teikyo University School of Medicine from January 2008 to July 2013 were retrospectively collected. All patients were divided into stable group (337 cases), slow progression group (337 cases) and rapid progression group (338 cases) according to the tertile of estimated glomerular filtration rate (eGFR) slope (the annual average percentage of eGFR decline). Multivariate logistic regression analysis models were used to evaluate the correlations of baseline serum potassium or time-averaged serum potassium level with CKD rapid progression. Results: Three hundred and forty-three cases from Tianjin First Central Hospital and 669 cases from Teikyo University School of Medicine were included in the study, and 635 cases (62.7%) were male. The average age was (61±14) years old and the average eGFR decline slope was 4.0%/year. The levels of baseline serum potassium and time-averaged serum potassium of patients in the slow progression group [(4.47±0.52) and (4.51±0.43) mmo/L] and rapid progression group [(4.62±0.62) and (4.76±0.48) mmo/L] were higher than those in the stable group [(4.37±0.49) and (4.38±0.37) mmo/L] (both P<0.05). Meanwhile, 24.6% (83/338) of the patients in the rapid progression group had hyperkalemia at baseline (serum potassium ≥5.0 mmol/L) and 34.9% (118/338) of the patients had time-averaged serum potassium ≥5.0 mmol/L, which were higher than those in the stable group [10.7% (36/337) and 6.5% (22/337)] (both P<0.001). Multivariate logistic regression analysis showed that compared with the stable group, baseline serum potassium (OR=1.843, 95%CI: 1.051-3.234) and time-averaged serum potassium (OR=2.495, 95%CI: 1.040-5.987) were correlated with the rapid progression of CKD. Time-averaged serum potassium ≥5.0 mmol/L was the independent influencing factor for rapid progression of CKD. Conclusions: During the follow-up period, the average level of serum potassium in stage Ⅲ-Ⅴ CKD patients should be controlled under 5.0 mmol/L, which may reduce the risk of rapid decline of renal function.

Low Serum Potassium Levels and Clinical Outcomes in Peritoneal Dialysis—International Results from PDOPPS

IntroductionHypokalemia, including normal range values <4 mEq/l, has been associated with increased peritonitis and mortality in patients with peritoneal dialysis. This study sought to describe international variation in hypokalemia, potential modifiable hypokalemia risk factors, and the covariate-adjusted relationship of hypokalemia with peritonitis and mortality.MethodsBaseline serum potassium was determined in 7421 patients from 7 countries in the Peritoneal Dialysis Outcomes and Practice Patterns Study (2014–2017). Association of baseline patient and treatment factors with subsequent serum potassium <4 mEq/l was evaluated by logistic regression, whereas baseline serum potassium levels (4-month average and fraction of 4 months having hypokalemia) on clinical outcomes was assessed by Cox regression.ResultsHypokalemia was more prevalent in Thailand and among black patients in the United States. Characteristics/treatments associated with potassium <4 mEq/l included protein-energy wasting indicators, lower urine volume, lower blood pressure, higher dialysis dose, greater diuretic use, and not being prescribed a renin-angiotensin system inhibitor. Persistent hypokalemia (all 4 months vs. 0 months over the 4-month exposure period) was associated with 80% higher subsequent peritonitis rates (at K <3.5 mEq/l) and 40% higher mortality (at K <4.0 mEq/l) after extensive case mix/potential confounding adjustments. Furthermore, adjusted peritonitis rates were higher if having mean serum K over 4 months <3.5 mEq/l versus 4.0–4.4 mEq/l (hazard ratio, 1.15 [95% confidence interval, 0.96–1.37]), largely because of Gram-positive/culture-negative infections.ConclusionsPersistent hypokalemia is associated with higher mortality and peritonitis even after extensive adjustment for patient factors. Further studies are needed to elucidate mechanisms of these poorer outcomes and modifiable risk factors for persistent hypokalemia.

Baseline and on-treatment serum potassium and mortality in high risk patients: the Systolic Blood Pressure Intervention Trial (SPRINT)

Abstract Background Observational studies in patients with hypertension have indicated a U-shaped association between on-treatment serum potassium levels and short-time mortality. However, the association between long-time mortality and serum potassium, and the potential modification of this association by intensive blood pressure lowering, are yet to be explored. Purpose To assess the relationship between serum potassium levels, treatment response to intensive blood pressure lowering, and mortality. Methods SPRINT was a randomized, controlled trial in which 9,361 individuals ≥50 years of age, at high cardiovascular (CV) risk, but without diabetes, who had an systolic blood pressure (SBP) 130–180 mmHg, were randomized to intensive (target SBP &amp;lt;120mmHg) or standard antihypertensive treatment (target SBP &amp;lt;140mmHg). Patients with an estimated glomerular filtration rate (eGFR) &amp;lt;25 ml/min/1.73 m2 or end-stage renal disease were excluded. Serum chemistry was drawn at baseline, prespecified intervals, and at close out. On-treatment serum potassium was defined as the last measurement for each participant. We examined the prognostic implications (for death from CV causes and death from any cause) of baseline and on-treatment serum potassium, using restricted cubic splines, unadjusted and adjusted for demographic, clinical, and laboratory variables. We further explored the effects of intensive blood pressure lowering across the serum potassium spectrum using interaction analyses. Results A total of 9,336 individuals had a serum potassium measurement available at baseline and 9,233 individuals had at least one subsequent measurement. Mean serum potassium was similar between the two study groups (intensive 4.21 mmol/l vs. standard 4.20 mmol/l; P=0.74); however, on-treatment serum potassium was significantly lower in the intensive group (intensive 4.17 mmol/l vs. standard 4.20 mmol/l; P=0.001). Median follow-up was 3.3 years (range 0–4.8), with 365 deaths from any cause (3.9%) and 102 deaths from CV causes (1.1%) recorded during the study period. Baseline serum potassium appeared to be linearly associated with both types of mortality events (test for overall trend, P&amp;lt;0.05; test for non-linearity versus linearity, P&amp;gt;0.05) on unadjusted analysis. On-treatment serum potassium displayed a U-shaped curve with death from any cause (test for overall trend, P=0.004; test for non-linearity versus linearity, P=0.006), but was not significantly associated with death from CV causes (P&amp;gt;0.05) (Figure). Associations were completely lost upon multivariable adjustment (P&amp;gt;0.05). This was particularly due to adjustment for eGFR. The efficacy of intensive blood pressure lowering was not modified by baseline or on-treatment serum potassium (P&amp;gt;0.05). Conclusions Neither baseline nor on-treatment serum potassium levels were associated with death after multivariable adjustment, including renal function. The efficacy of intensive blood pressure lowering was not modified by serum potassium. Serum Potassium and death Funding Acknowledgement Type of funding source: None

Efficacy and safety of sodium zirconium cyclosilicate in patients with baseline serum potassium level \u2265 5.5 mmol/L: pooled analysis from two phase 3 trials

BackgroundReliable, timely-onset, oral treatments with an acceptable safety profile for patients with hyperkalemia are needed. We examined the efficacy and safety of sodium zirconium cyclosilicate (SZC; formerly ZS-9) treatment for ≤ 48 h in patients with baseline serum potassium level ≥ 5.5 mmol/L.MethodsData were pooled from two phase 3 studies (ZS-003 and HARMONIZE) among patients receiving SZC 10 g three times daily. Outcomes included mean and absolute change from baseline, median time to potassium level ≤ 5.5 and ≤ 5.0 mmol/L, and proportion achieving potassium level ≤ 5.5 and ≤ 5.0 mmol/L at 4, 24, and 48 h. Outcomes were stratified by baseline potassium. Safety outcomes were evaluated.ResultsAt baseline, 125 of 170 patients (73.5%) had potassium level 5.5–< 6.0, 39 (22.9%) had potassium level 6.0–6.5, and 6 (3.5%) had potassium level > 6.5 mmol/L. Regardless of baseline potassium, mean potassium decreased at 1 h post-initial dose. By 4 and 48 h, 37.5% and 85.0% of patients achieved potassium level ≤ 5.0 mmol/L, respectively. Median (95% confidence interval) times to potassium level ≤ 5.5 and ≤ 5.0 mmol/L were 2.0 (1.1–2.0) and 21.6 (4.1–22.4) h, respectively. Fifteen patients (8.8%) experienced adverse events; none were serious.ConclusionsSZC 10 g three times daily achieved serum potassium reduction and normokalemia, with a favorable safety profile.Trial registrationClinicalTrials.gov identifiers: ZS-003: NCT01737697 and HARMONIZE: NCT02088073.

Racial and Ethnic Differences in Mortality Associated with Serum Potassium in Incident Peritoneal Dialysis Patients

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.

STUDY ON EFFECTS OF REPEATED SALBUTAMOL NEBULIZATIONS ON SERUM POTASSIUM LEVELS AND QTC ON ELECTROCARDIOGRAM IN CHILDREN WITH ACUTE WHEEZE

Objective: Acute wheeze is a common problem in young children with respiratory disorders. This study emphasizes on whether there are any significant changes in serum potassium levels and QTc interval during repeated salbutamol nebulizations. Methods: A cross-sectional observational study was conducted at a tertiary care teaching hospital. The study group comprised of 41 children in the age group of 6 months–12 years. Pediatric asthma score and vital parameters (heart rate, respiratory rate, and SpO2) were recorded at the onset and end of salbutamol nebulizations. Baseline serum potassium levels were taken at the onset and then at the end. An electrocardiogram (ECG) was taken at 1 h and another at 3 h, for those who continued to require repeated nebulizations until then. Results: The mean fall in serum potassium levels after repeated salbutamol nebulizations was 0.3±0.4 (p<0.05). The mean fall after 3, 4, 5, and 6 salbutamol nebulizations was 0.06, 0.44, 0.66, and 0.43 mEq/L, respectively. There were no significant changes in ECG patterns in these children. The mean QTc at 1 h of repeated salbutamol nebulizations was 0.41±0.02 (s) and that after 3 h (for children requiring repeated nebulizations until then) was 0.43±0.01 (s). The mean rise in QTc at 3 h was 0.004 s, which was not statistically significant (p=0.137). Conclusion: We conclude that serum potassium levels should be monitored in children receiving repeated salbutamol nebulizations for acute wheeze.

Reduced Versus Conventional Dose Insulin for Hyperkalemia Treatment

Background: Using a reduced dose of 5 units of regular insulin has been proposed as a strategy to mitigate the risk of hypoglycemia when treating hyperkalemia. The comparative efficacy and safety of this strategy to conventional 10 units is not well established. Objective: To compare the effectiveness of reduced and conventional dosed insulin for hyperkalemia treatment. Methods: Electronic medication administration reports of conventional or reduced doses of insulin given for hyperkalemia treatment were reviewed from July 2013 to September 2015. The primary outcome was reduction in serum potassium. Results: Ninety-two administrations of reduced dose insulin and 309 administrations of conventional dose insulin were included. No significant difference was found in potassium reduction between the groups (−0.096 mmol/L, P value = .2210). Post hoc subgroup analysis of patients with serum potassium > 6 mmol/L revealed a lower reduction in potassium in the reduced dose group compared to the conventional dose group (difference: −0.238 mmol/L, P value = .018). Conclusions Conventional dose insulin may be more effective than reduced dose regular insulin at baseline serum potassium levels >6 mmol/L in the treatment of hyperkalemia. Frequent monitoring of serum potassium and glucose after administration of insulin is necessary to confirm adequate response and avoidance of hypoglycemia.

Elevated baseline potassium level within reference range is associated with worse clinical outcomes in hospitalised patients

The clinical significance of elevated baseline serum potassium (K+) levels in hospitalised patients is rarely described. Hence, we performed a retrospective study assessing the significance of elevated K+ levels in a one-year admission cohort. Adult patients without hypokalaemia or end-stage renal disease were included. Adverse outcomes were all-cause mortality, hospital-acquired acute kidney injury, and events of arrhythmia. In total, 17,777 patients were included in the study cohort, and a significant difference (P < 0.001) was observed in mortality according to baseline serum K+ levels. The adjusted hazard ratios (HRs) and associated 95% confidence intervals (CIs) of all-cause mortality for K+ levels above the reference range of 3.6–4.0 mmol/L were as follows: 4.1–4.5 mmol/L, adjusted HR 1.075 (95% CI 0.981–1.180); 4.6–5.0 mmol/L, adjusted HR 1.261 (1.105–1.439); 5.1–5.5 mmol/L, adjusted HR 1.310 (1.009–1.700); >5.5 mmol/L, adjusted HR 2.119 (1.532–2.930). Moreover, the risks of in-hospital acute kidney injury and arrhythmia were higher in patients with serum K+ levels above 4.0 mmol/L and 5.5 mmol/L, respectively. In conclusion, increased serum K+ levels, including mild elevations may be related to worse prognosis. Close monitoring and prompt correction of underlying causes or hyperkalaemia itself is warranted for admitted patients.

Racial and Ethnic Differences in Mortality Associated with Serum Potassium in a Large Hemodialysis Cohort

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and Diabetic Kidney Disease

ImportanceHyperkalemia is a potentially life-threatening condition predominantly seen in patients treated with renin-angiotensin-aldosterone system (RAAS) inhibitors with stage 3 or greater chronic kidney disease (CKD) who may also have diabetes, heart failure, or both.ObjectivesTo select starting doses for a phase 3 study and to evaluate the long-term safety and efficacy of a potassium-binding polymer, patiromer, in outpatients with hyperkalemia.Design, Setting, and ParticipantsPhase 2, multicenter, open-label, dose-ranging, randomized clinical trial (AMETHYST-DN), conducted at 48 sites in Europe from June 2011 to June 2013 evaluating patiromer in 306 outpatients with type 2 diabetes (estimated glomerular filtration rate, 15 to <60 mL/min/1.73 m2 and serum potassium level >5.0 mEq/L). All patients received RAAS inhibitors prior to and during study treatment.InterventionsPatients were stratified by baseline serum potassium level into mild or moderate hyperkalemia groups and received 1 of 3 randomized starting doses of patiromer (4.2 g [n = 74], 8.4 g [n = 74], or 12.6 g [n = 74] twice daily [mild hyperkalemia] or 8.4 g [n = 26], 12.6 g [n = 28], or 16.8 g [n = 30] twice daily [moderate hyperkalemia]). Patiromer was titrated to achieve and maintain serum potassium level 5.0 mEq/L or lower.Main Outcomes and MeasuresThe primary efficacy end point was mean change in serum potassium level from baseline to week 4 or prior to initiation of dose titration. The primary safety end point was adverse events through 52 weeks. Secondary efficacy end points included mean change in serum potassium level through 52 weeks.ResultsA total of 306 patients were randomized. The least squares mean reduction from baseline in serum potassium level at week 4 or time of first dose titration in patients with mild hyperkalemia was 0.35 (95% CI, 0.22-0.48) mEq/L for the 4.2 g twice daily starting-dose group, 0.51 (95% CI, 0.38-0.64) mEq/L for the 8.4 g twice daily starting-dose group, and 0.55 (95% CI, 0.42-0.68) mEq/L for the 12.6 g twice daily starting-dose group. In those with moderate hyperkalemia, the reduction was 0.87 (95% CI, 0.60-1.14) mEq/L for the 8.4 g twice daily starting-dose group, 0.97 (95% CI, 0.70-1.23) mEq/L for the 12.6 g twice daily starting-dose group, and 0.92 (95% CI, 0.67-1.17) mEq/L for the 16.8 g twice daily starting-dose group (P < .001 for all changes vs baseline by hyperkalemia starting-dose groups within strata). From week 4 through week 52, statistically significant mean decreases in serum potassium levels were observed at each monthly point in patients with mild and moderate hyperkalemia. Over the 52 weeks, hypomagnesemia (7.2%) was the most common treatment-related adverse event, mild to moderate constipation (6.3%) was the most common gastrointestinal adverse event, and hypokalemia (<3.5 mEq/L) occurred in 5.6% of patients.Conclusions and RelevanceAmong patients with hyperkalemia and diabetic kidney disease, patiromer starting doses of 4.2 to 16.8 g twice daily resulted in statistically significant decreases in serum potassium level after 4 weeks of treatment, lasting through 52 weeks.Trial Registrationclinicaltrials.gov Identifier: NCT01371747

Associations between serum potassium and sodium levels and risk of hypertension: a community-based cohort study.

ObjectiveSeveral studies have examined the relationships between dietary potassium and sodium and hypertension, but few have evaluated the association between serum potassium or sodium and risk of incident hypertension. We therefore investigated the associations between serum potassium and sodium and risk of incident hypertension in a Chinese community-based population.MethodsA total of 839 normotensive individuals without cardiovascular disease from the Chinese Multi-Provincial Cohort Study who took part in the baseline examination in 2007–2008 and the follow-up survey in 2012–2013 were included in this study. Odds ratios (OR) and 95% confidence intervals (95%CI) for baseline serum potassium and sodium in relation to the risk of new-onset hypertension were evaluated using multivariate logistic regression models.ResultsDuring five years of follow-up, 218 (26.0%) individuals progressed to hypertension. Logistic regression adjusting for multiple confounders showed that every 1 mEq/L increment in baseline serum potassium level was associated with a 75% increased risk of hypertension (OR: 1.75; 95%CI: 1.01–3.04; P = 0.04). Compared with adults with serum potassium level of 4.20–4.79 mEq/L, adults with level ≥ 4.80 mEq/L had an 84% increased risk of hypertension (OR: 1.84; 95%CI: 1.14–2.96; P = 0.01). There was no significant association between serum sodium and risk of hypertension (OR: 0.96; 95%CI: 0.89–1.04; P = 0.33).ConclusionsBaseline serum potassium level, but not baseline serum sodium level, was positively related to the risk of incident hypertension in the Chinese population.

ACID BASE, ION DISORDERS, LITHISASIS

Introduction and Aims: Hyperkalaemia is a risk factor for mortality in patients with cardiovascular disease and chronic kidney disease (CKD) (Goyal, 2012; Torlen, 2012) and limits use of renin-angiotensin-aldosterone system inhibitors (RAASi) in these patients. Sodium (or calcium) polystyrene sulfonate (SPS/CPS) has uncertain efficacy and has been associated with substantial adverse events, as well as poor gastrointestinal tolerability, and hence is suboptimal for acute use and unsuitable for chronic use (Harel, 2013; Sterns, 2010). Therefore, there is a need for a hyperkalaemia treatment that rapidly reduces serum potassium (K+) and is safe and well tolerated in these patients. ZS-9, a nonabsorbed cation exchanger designed to specifically entrap excess K +, significantly reduced K+ vs placebo over 48 hr with excellent tolerability in patients with CKD (Ash, 2013). We report acute-phase efficacy in a Phase 3 trial of ZS-9 in patients with hyperkalemia. Methods: Patients (N=753) with serum K+ 5.0-6.5 mmol/L were randomised (1:1:1:1:1) to ZS-9 (1.25g, 2.5g, 5g or 10g) or placebo given three times daily (TID) with meals for 48 hr (acute phase), after which those with K+ ≤4.9 mmol/L (n=542) were re-randomised to ZS-9 or placebo once daily for Day 3-15. Serum K+ was measured at baseline and at predefined intervals, including 1, 4, 24, and 48 hr after the first dose. The acute-phase primary efficacy endpoint was the rate of K+ change over the first 48 hr, using longitudinal modeling to account for all post-baseline data. Results:Mean K+ at baseline was 5.3 mmol/L. Substantial percentages of patients had CKD (60%), a history of heart failure (40%), or diabetes (60%) or were on RAASi therapy (67%). ZS-9 demonstrated significant dose-dependent reductions in K+; the acute-phase primary efficacy endpoint was met for ZS-9 2.5g (p=0.0009), 5g (p<0.0001) and 10g TID (p<0.0001; Fig. 1). There was a significant decrease in K+ by -0.11 mmol/L with ZS-9 10g vs an increase of +0.01 mmol/L with placebo (p=0.009) 1 hr after the first dose. At 48 hr K+ fell by -0.73 mmol/L with 10g TID vs -0.25 mmol/L with placebo (p<0.001); other significant reductions vs placebo are shown in Fig 2. Rates of all adverse events (AEs) and gastrointestinal AEs were not significantly different in the ZS-9 and placebo groups. Conclusions: ZS-9 produced significant dose-dependent reductions in K+ when given TID for 48 hr, with an AE profile similar to placebo. The significant reduction in serum K+ 1 hr after the first ZS-9 10g dose further suggests that ZS-9 is effective in removing K+ from the small intestine fluid, where it is in equilibrium with blood levels. ZS-9 may address an important unmet clinical need by rapidly correcting hyperkalaemia in high-risk patients, many of whom require RAASi for end-organ protection. SP321 PHASE 3, MULTICENTER, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIALOF ZS-9: SUBGROUP ANALYSIS STRATIFIED BY BASELINE SERUM POTASSIUM LEVELS

Serum potassium levels predict blood pressure response to aldosterone antagonists in resistant hypertension

The objective of this study was to identify factors associated with the blood pressure (BP) response to spironolactone--aldosterone receptor antagonist as an add-on therapy in patients with resistant hypertension (HTN). We retrospectively reviewed the data of subjects with resistant HTN who were treated with add-on spironolactone in a large HTN clinic. A paired Student's t-test was used to assess the differences between the BP values before and during spironolactone administration, and multivariate analysis was used to assess the predictors of a satisfactory BP response (a decrease in systolic BP >10%). We analyzed the data of 48 hypertensive participants. The add-on spironolactone therapy had a significant BP-lowering effect in both systolic and diastolic BP values (P < 0.01 for both). Baseline serum potassium levels of <4.5 mEq l(-1) were associated with a satisfactory BP response (P < 0.01). Furthermore, every decrement of 1 mEq l(-1) of serum potassium was independently associated with a fivefold higher rate of achieving a satisfactory BP response to spironolactone therapy (P = 0.024). Additional factors independently associated with an improved systolic BP response were old age (P = 0.033), body mass index (P = 0.033) and high baseline systolic BP (P=0.004). Our results support the use of add-on spironolactone therapy in patients with resistant HTN who are elderly and obese and have high systolic BP and serum potassium levels <4.5 mEq l(-1).