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Association between potassium supplementation and the occurrence of acute kidney injury in patients with hypokalemia administered liposomal amphotericin B: a nationwide observational study.
Ota, Y, Obata, Y, Takazono, T, Tashiro, M, Wakamura, T, Takahashi, A, Shiozawa, Y, Miyazaki, T, Nishino, T, Izumikawa, K
BMC nephrology. 2021;(1):240
Abstract
BACKGROUND Hypokalemia and acute kidney injury (AKI) occur in patients administered liposomal amphotericin B (L-AMB), a wide-spectrum anti-fungicidal drug. However, the association between potassium supplementation and the occurrence of AKI in patients with hypokalemia who were administered L-AMB is not well understood. METHODS Using nationwide claims data and laboratory data, the occurrence of AKI during L-AMB treatment was retrospectively compared between patients with hypokalemia who were or were not supplemented with potassium and between those adequately or inadequately supplemented with potassium (serum potassium levels corrected to ≥3.5 mEq/L or remained < 3.5 mEq/L, respectively) before or after L-AMB treatment initiation. RESULTS We identified 118 patients who developed hypokalemia before L-AMB treatment initiation (43 received potassium supplementation [25 adequate and 18 inadequate supplementation] and 75 did not receive potassium supplementation), and 117 patients who developed hypokalemia after L-AMB initiation (79 received potassium supplementation [including 23 adequate and 15 inadequate supplementation] and 38 did not receive potassium supplementation). The occurrence of any stage of AKI was similar between patients with hypokalemia, regardless of potassium supplementation (i.e., before L-AMB treatment initiation [supplementation, 51%; non-supplementation, 45%; P = 0.570] or after L-AMB initiation [supplementation, 28%; non-supplementation, 32%; P = 0.671]). After adjusting for confounding factors, we found that the occurrence of any stage of AKI was not associated with potassium supplementation before L-AMB initiation (odds ratio [OR]: 1.291, 95% confidence interval [CI]: 0.584-2.852, P = 0.528) or after L-AMB initiation (OR: 0.954, 95% CI: 0.400-2.275, P = 0.915). The occurrence of any stage of AKI tended to decline in patients with hypokalemia who were adequately supplemented with potassium (44%) before, but not after, L-AMB initiation relative to that in patients inadequately supplemented with potassium (61%), however this result was not significant (P = 0.358). CONCLUSION Potassium supplementation was not associated with any stage of AKI in patients with hypokalemia who were administered L-AMB.
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Emergency Potassium Normalization Treatment Including Sodium Zirconium Cyclosilicate: A Phase II, Randomized, Double-blind, Placebo-controlled Study (ENERGIZE).
Peacock, WF, Rafique, Z, Vishnevskiy, K, Michelson, E, Vishneva, E, Zvereva, T, Nahra, R, Li, D, Miller, J
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2020;(6):475-486
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OBJECTIVES Sodium zirconium cyclosilicate (SZC) is a novel, highly selective potassium binder currently approved in the United States and European Union for treatment of hyperkalemia. This pilot evaluation explored the efficacy of SZC with insulin and glucose as hyperkalemia treatment in the emergency department (ED). METHODS This exploratory, phase II, multicenter, randomized, double-blind, placebo-controlled study (NCT03337477) enrolled adult ED patients with blood potassium ≥ 5.8 mmol/L. Patients were randomized 1:1 to receive SZC 10 g or placebo, up to three times during a 10-hour period, with insulin and glucose. The primary efficacy outcome was the mean change in serum potassium (sK+ ) from baseline until 4 hours after start of dosing. RESULTS Overall, 70 patients were randomized (SZC n = 33, placebo n = 37), of whom 50.0% were male. Their mean (± standard deviation [±SD]) age was 59.0 (±13.8) years and mean initial sK+ was similar between groups (SZC 6.4 mmol/L, placebo 6.5 mmol/L). The least squares mean (±SD) sK+ change from baseline to 4 hours was -0.41 (±0.11) mmol/L and -0.27 (±0.10) mmol/L with SZC and placebo, respectively (difference = -0.13 mmol/L, 95% confidence interval [CI] = -0.44 to 0.17). A greater reduction in mean (±SD) sK+ from baseline occurred with SZC compared with placebo at 2 hours: -0.72 (±0.12) versus -0.36 (±0.11) mmol/L (LSM difference = -0.35 mmol/L, 95% CI = -0.68 to -0.02), respectively. A numerically lower proportion of patients in the SZC group required additional potassium-lowering therapy due to hyperkalemia at 0 to 4 hours versus placebo (15.6% vs. 30.6%, respectively; odds ratio = 0.40, 95% CI = 0.09 to 1.77). Comparable proportions of patients experienced adverse events in both treatment groups at 0 to 24 hours. CONCLUSIONS This pilot study suggested that SZC with insulin and glucose may provide an incremental benefit in the emergency treatment of hyperkalemia over insulin and glucose alone.
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Kidney Function and Potassium Monitoring After Initiation of Renin-Angiotensin-Aldosterone System Blockade Therapy and Outcomes in 2 North American Populations.
Parikh, RV, Nash, DM, Brimble, KS, Markle-Reid, M, Tan, TC, McArthur, E, Khoshniat-Rad, F, Sood, MM, Zheng, S, Pravoverov, L, et al
Circulation. Cardiovascular quality and outcomes. 2020;(9):e006415
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BACKGROUND Clinical practice guidelines recommend routine kidney function and serum potassium testing within 30 days of initiating ACE (angiotensin-converting enzyme) inhibitor or angiotensin II receptor blocker therapy. However, evidence is lacking about whether follow-up testing reduces therapy-related adverse outcomes. METHODS AND RESULTS We conducted 2 population-based retrospective cohort studies in Kaiser Permanente Northern California and Ontario, Canada. Patients with outpatient serum creatinine and potassium tests in the 30 days after starting ACE inhibitor or angiotensin II receptor blocker therapy were matched 1:1 to patients without follow-up tests. We evaluated the association of follow-up testing with 30-day all-cause mortality and hospitalization with acute kidney injury or hyperkalemia using Cox regression. We also developed and externally validated a risk score to identify patients at risk of having abnormally high serum creatinine and potassium values in follow-up. We identified 75 251 matched pairs initiating ACE inhibitor or angiotensin II receptor blocker therapy between January 1, 2007, and December 31, 2017, in Kaiser Permanente Northern California. Follow-up testing was not significantly associated with 30-day all-cause mortality in Kaiser Permanente Northern California (hazard ratio, 0.75 [95% CI, 0.54-1.06]) and was associated with higher mortality in 84 905 matched pairs in Ontario (hazard ratio, 1.32 [95% CI, 1.07-1.62]). In Kaiser Permanente Northern California, follow-up testing was significantly associated with higher rates of hospitalization with acute kidney injury (hazard ratio, 1.66 [95% CI, 1.10-2.22]) and hyperkalemia (hazard ratio, 3.36 [95% CI, 1.08-10.41]), as was observed in Ontario. The risk score for abnormal potassium provided good discrimination (area under the curve [AUC], 0.75) and excellent calibration of predicted risks, while the risk score for abnormal serum creatinine provided moderate discrimination (AUC, 0.62) but excellent calibration. CONCLUSIONS Routine laboratory monitoring after ACE inhibitor or angiotensin II receptor blocker initiation was not associated with a lower risk of 30-day mortality. We identified patient subgroups in which targeted testing may be effective in identifying therapy-related changes in serum potassium or kidney function.
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Serum potassium level on hospital arrival and survival after out-of-hospital cardiac arrest: The CRITICAL study in Osaka, Japan.
Shida, H, Matsuyama, T, Iwami, T, Okabayashi, S, Yamada, T, Hayakawa, K, Yoshiya, K, Irisawa, T, Noguchi, K, Nishimura, T, et al
European heart journal. Acute cardiovascular care. 2020;(4_suppl):S175-S183
Abstract
BACKGROUND Little is known about the association between serum potassium level on hospital arrival and neurological outcome after out-of-hospital cardiac arrest (OHCA). We investigated whether the serum potassium level on hospital arrival had prognostic indications for patients with OHCA. METHODS This prospective, multicenter observational study conducted in Osaka, Japan (CRITICAL study) enrolled consecutive patients with OHCA transported to 14 participating institutions from 2012 to 2016. We included adult patients aged ⩾18 years with OHCA of cardiac origin who achieved return of spontaneous circulation and whose serum potassium level on hospital arrival was available. Based on the serum potassium level, patients were divided into four quartiles: Q1 (K ⩽3.8 mEq/L), Q2 (3.8< K⩽4.5 mEq/L), Q3 (4.5< K⩽5.6 mEq/L) and Q4 (K >5.6 mEq/L). The primary outcome was one-month survival with favorable neurological outcome, defined as cerebral performance category scale 1 or 2. RESULTS A total of 9822 patients were registered, and 1516 of these were eligible for analyses. The highest proportion of favorable neurological outcome was 44.8% (189/422) in Q1 group, followed by 30.3% (103/340), 11.7% (44/375) and 4.5% (17/379) in the Q2, Q3 and Q4 groups, respectively (p<0.001). In the multivariable analysis, the proportion of favorable neurological outcome decreased as the serum potassium level increased (p<0.001). CONCLUSIONS High serum potassium level was significantly and dose-dependently associated with poor neurological outcome. Serum potassium on hospital arrival would be one of the effective prognostic indications for OHCA achieving return of spontaneous circulation.
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Accuracy of Hemolyzed Potassium Levels in the Emergency Department.
Wilson, M, Adelman, S, Maitre, JB, Izzo, J, Valencia, R, Yang, M, Dubin, J, Goyal, M
The western journal of emergency medicine. 2020;(6):272-275
Abstract
INTRODUCTION In the emergency department (ED), pseudohyperkalemia from hemolysis may indirectly harm patients by exposing them to increased length of stay, cost, and repeat blood draws. The need to repeat hemolyzed potassium specimens in low-risk patients has not been well studied. Our objective was to determine the rate of true hyperkalemia among low-risk, adult ED patients with hemolyzed potassium specimens. METHODS We conducted this prospective observational study at two large (129,000 annual visits) academic EDs in the mid-Atlantic. Data were collected from June 2017-November 2017 as baseline data for planned departmental quality improvement and again from June 2018-November 2018. Inclusion criteria were an initial basic metabolic panel in the ED with a hemolyzed potassium level > 5.1 milliequivalents per liter that was repeated within 12 hours, age (≥18, and bicarbonate (HCO3) > 20. Exclusion criteria were age > 65, glomerular filtration rate (GFR) < 60, creatine phosphokinase > 500, hematologic malignancy, taking potassium-sparing or angiotensin-acting agents, or treatment with potassium-lowering agents (albuterol, insulin, HCO3, sodium polystyrene sulfonate, or potassium-excreting diuretic) prior to the repeat lab draw. RESULTS Of 399 encounters with a hemolyzed, elevated potassium level in patients with GFR ≥ 60 and age > 18 that were repeated, we excluded 333 patients for age > 64, lab repeat > 12 hours, invalid identifiers, potassium-elevating or lowering medicines or hematologic malignancies.This left 66 encounters for review. There were no instances of hyperkalemia on the repeated, non-hemolyzed potassium levels, correlating to a true positive rate of 0% (95% confidence interval 0-6%). Median patient age was 46 (interquartile range [IQR] 34 - 56) years. Median hemolyzed potassium level was 5.8 (IQR 5.6 - 6.15) millimoles per liter (mmol/L), and median repeated potassium level was 3.9 (IQR 3.6 - 4.3) mmol/L. Median time between lab draws was 145 (IQR 87 - 262) minutes. CONCLUSION Of 66 patients who met our criteria, all had repeat non-hemolyzed potassiums within normal limits. The median of 145 minutes between lab draws suggests an opportunity to decrease the length of stay for these patients. Our results suggest that in adult patients < 65 with normal renal function, no hematologic malignancy, and not on a potassium-elevating medication, there is little to no risk of true hyperkalemia. Further studies should be done with a larger patient population and multicenter trials.
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Association of hypokalemia with an increased risk for medically treated arrhythmias.
Phillips, CT, Wang, J, Celi, LA, Zhang, Z, Feng, M
PloS one. 2019;(6):e0217432
Abstract
BACKGROUND Potassium replenishment protocols are often employed across broad patient populations to prevent cardiac arrhythmias. Tailoring potassium thresholds to specific patient populations would reduce unnecessary tasks and cost. The objective of this retrospective cohort study was to determine the threshold at which hypokalemia increases the risk for medically treated arrhythmias in cardiac versus medical and surgical intensive care units. METHODS Patients captured in the publicly available Philips eICU database were assessed for initiation of either intravenous amiodarone, adenosine, ibutilide, isoproterenol, or lidocaine as a surrogate for a clinically significant arrhythmia. A landmark time-to-event analysis was conducted to investigate the association of serum potassium values and time-marked administration of an antiarrhythmic drug. Analysis was adjusted for comorbidities, the use of vasopressor agents, diuretics, as well as age, gender and severity of illness. RESULTS Among 20,665 admissions to cardiac intensive care units, 1,371 (6.6%) were treated with either amiodarone, adenosine, ibutilide, isoproterenol, or lidocaine. For potassium values of ≥3.0<3.5mEq/L, antiarrhythmic treatment occurred at an increased rate compared to a baseline of ≥4.0≤5.0mEq/L (HR 1.23, 95% CI 1.01-1.51; P = 0.04). For admissions to medical and surgical intensive care units, 2,100 of 69,714 patients (3.0%) were treated with either amiodarone, adenosine, ibutilide, isoproterenol, or lidocaine. Potassium values of ≥3.0<3.5mEq/L were also associated with an increased hazard of treatment (HR 1.26, 95% CI 1.09-1.45; P = 0.002). In both cohorts, worsening hypokalemia was associated with an increased risk of antiarrhythmic drug treatment. In neither cohort were there statistically significant differences for serum potassium values of ≥3.5<4.0 and a baseline of ≥4.0≤5.0mEq/L. The proportion of patients initiated on vasopressors or inotropes was over four-fold higher in those treated with one of the antiarrhythmic drugs in both cohorts. CONCLUSIONS Serum potassium levels <3.5mEq/L were associated with an increased hazard for treatment with specific antiarrhythmic drugs in a large cohort of patients admitted to both a cardiac as well as medical and surgical intensive care units. Potassium thresholds may be individualized further based on risk of relevant outcomes.
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Serum potassium and clinical outcomes in heart failure patients: results of risk calculations in 21 334 patients in the UK.
Linde, C, Qin, L, Bakhai, A, Furuland, H, Evans, M, Ayoubkhani, D, Palaka, E, Bennett, H, McEwan, P
ESC heart failure. 2019;(2):280-290
Abstract
AIMS: 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. METHODS AND RESULTS 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. CONCLUSIONS 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.
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Daily urinary sodium and potassium excretion in Chinese first-generation migrants in Italy.
Modesti, PA, Marzotti, I, Rapi, S, Rogolino, A, Cappuccio, FP, Zhao, D, Costanzo, G, Galanti, G, Boddi, M
International journal of cardiology. 2019;:175-180
Abstract
BACKGROUND China has one of the highest salt intake levels in the world, and Chinese people form one of the largest foreign-born communities now living in Europe. The present study was performed to assess 24-hour urinary sodium and potassium excretion in Chinese migrants in Italy and to explore possible associations with hypertension, hypertension awareness, and length of residence in Italy. METHODS A cross-sectional evaluation was conducted on 319 first-generation Chinese migrants (154 women and 165 men) aged 18-70 years. Subjects were asked to do a 24-hour urine collection and the relationships of urinary sodium and potassium and arterial blood pressure, hypertension (BP ≥ 140/90 mmHg or anti-hypertensive drug use), hypertension awareness, and years of residence in Italy were investigated with linear or logistic regression analysis. RESULTS Sodium excretion was 145.2 mmol/day (95%CI 138.0-152.3) in men, and 134.7 (95%CI 127.6-141.8) in women corresponding to a dietary salt intake of 9.4 g/day (95%CI 9.0-9.9) and 8.8 (95%CI 8.3-9.2) respectively. Potassium excretion was 35.1 mmol/day (95%CI 33.6-36.5), with no significant difference by gender. At multivariable adjusted linear regression analysis body mass index, low education level, and hypertension were positive predictors of sodium urinary excretion; gender (women), and body mass index were positive predictors of potassium excretion. Sodium and potassium excretion were unaffected by hypertension awareness or years of residence in Italy. CONCLUSIONS Sodium excretion in Chinese workers is higher than recommended and in line with high salt intake in Italy. Potassium consumption remains low.
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Urinary Potassium Excretion and Progression of CKD.
Kim, HW, Park, JT, Yoo, TH, Lee, J, Chung, W, Lee, KB, Chae, DW, Ahn, C, Kang, SW, Choi, KH, et al
Clinical journal of the American Society of Nephrology : CJASN. 2019;(3):330-340
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BACKGROUND AND OBJECTIVES Data on whether low or high urinary potassium excretion is associated with poor kidney outcome have been conflicting. The aim of this study was to clarify the association between urinary potassium excretion and CKD progression. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We investigated the relationship between lower urinary potassium excretion and CKD progression and compared three urinary potassium indices among 1821 patients from the Korean Cohort Study for Outcome in Patients with CKD. Urinary potassium excretion was determined using spot urinary potassium-to-creatinine ratio, spot urinary potassium concentration, and 24-hour urinary potassium excretion. Patients were categorized into four groups according to quartiles of each urinary potassium excretion metric. The study end point was a composite of a ≥50% decrease in eGFR from baseline values and ESKD. RESULTS During 5326 person-years of follow-up, the primary outcome occurred in 392 (22%) patients. In a multivariable cause-specific hazard model, lower urinary potassium-to-creatinine ratio was associated with higher risk of CKD progression (adjusted hazard ratio, 1.47; 95% confidence interval, 1.01 to 2.12) comparing the lowest quartile with the highest quartile. Sensitivity analyses with other potassium metrics also showed consistent results in 855 patients who completed 24-hour urinary collections: adjusted hazard ratios comparing the lowest quartile with the highest quartile were 3.05 (95% confidence interval, 1.54 to 6.04) for 24-hour urinary potassium excretion, 1.95 (95% confidence interval, 1.05 to 3.62) for spot urinary potassium-to-creatinine ratio, and 3.79 (95% confidence interval, 1.51 to 9.51) for spot urinary potassium concentration. CONCLUSIONS Low urinary potassium excretion is associated with progression of CKD.
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Effect of Patiromer in Hyperkalemic Patients Taking and Not Taking RAAS Inhibitors.
Kloner, RA, Gross, C, Yuan, J, Conrad, A, Pergola, PE
Journal of cardiovascular pharmacology and therapeutics. 2018;(6):524-531
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INTRODUCTION Hyperkalemia (potassium >5.0 mEq/L) affects heart failure patients with renal disease regardless of the use of renin-angiotensin-aldosterone system inhibitors (RAASi). The open-label TOURMALINE study showed that patiromer, a sodium-free, nonabsorbed potassium binder, lowers serum potassium of hyperkalemic patients similarly when given with or without food; unlike prior studies, patients were not required to be taking RAASi. We conducted post hoc analyses to provide the first report of patiromer in patients not taking RAASi. METHODS Hyperkalemic patients received patiromer, 8.4 g/d to start, adjusted to achieve and maintain serum potassium of 3.8 to 5.0 mEq/L. If taking RAASi, stable doses were required. The primary end point was the proportion of patients with serum potassium 3.8 to 5.0 mEq/L at week 3 or 4. This analysis presents data by patients taking or not taking RAASi. RESULTS Demographics and baseline characteristics were similar in patients taking (n = 67) and not taking RAASi (n = 45). Baseline mean (SD) serum potassium was 5.37 (0.37) mEq/L and 5.42 (0.43) mEq/L in patients taking and not taking RAASi, respectively. Mean (SD) daily patiromer doses were similar (10.7 [3.2] and 11.5 [4.0] g, respectively). The primary end point was achieved in 85% (95% confidence interval [CI]: 74-93) of patients taking RAASi and in 84% (95% CI: 71-94) of patients not taking RAASi. From baseline to week 4, the mean (SE) change in serum potassium was -0.67 (0.08) mEq/L in patients taking RAASi and -0.56 (0.10) mEq/L in patients not taking RAASi (both P < .0001 vs baseline, P = nonsignificant between groups). Adverse events were reported in 26 (39%) patients taking RAASi and 25 (54%) not taking RAASi; the most common adverse event was diarrhea (2% and 11%, respectively; no cases were severe). Five patients (2 taking RAASi) reported 6 serious adverse events; none considered related to patiromer. CONCLUSIONS Patiromer was effective and generally well-tolerated for hyperkalemia treatment, whether or not patients were taking RAAS inhibitors.