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1.
BMC Emerg Med ; 24(1): 95, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824546

ABSTRACT

OBJECTIVE: This study assesses the influence of hyperkalemia on both disease severity and the risk of mortality among patients admitted to the emergency room. METHODS: This retrospective observational study utilized data from the Chinese Emergency Triage Assessment and Treatment database (CETAT, version 2.0), which was designed to evaluate and optimize management strategies for emergency room (ER) patients. Patients were systematically categorized based on serum potassium levels. Relationships between serum potassium levels, risk of mortality, and the severity of illness were then analyzed using multifactorial logistic regression and through Receiver Operating Characteristic (ROC) analysis. The effectiveness of various treatments at lowering potassium levels was also investigated. RESULTS: 12,799 emergency patients were enrolled, of whom 20.1% (n = 2,577) were hypokalemic and 2.98% (n = 381) were hyperkalemic. Among hyperkalemic patients, the leading reasons for visiting the ER were altered consciousness 23.88% (n = 91), cardiovascular symptoms 22.31% (n = 85), and gastrointestinal symptoms 20.47% (n = 78). Comparative analysis with patients exhibiting normal potassium levels revealed hyperkalemia as an independent factor associated with mortality in the ER. Mortality risk appears to positively correlate with increasing potassium levels, reaching peaks when blood potassium levels ranged between 6.5 and 7.0. Hyperkalemia emerged as a strong predictor of death in the ER, with an Area Under the Curve (AUC) of 0.89. The most frequently prescribed treatment for hyperkalemia patients was diuretics (57.32%, n = 188), followed by intravenous sodium bicarbonate (50.91%, n = 167), IV calcium (37.2%, n = 122), insulin combined with high glucose (27.74%, n = 91), and Continuous Renal Replacement Therapy (CRRT) for 19.82% (n = 65). Among these, CRRT appeared to be the most efficacious at reducing potassium levels. Diuretics appeared relatively ineffective, while high-glucose insulin, sodium bicarbonate, and calcium preparations having no significant effect on the rate of potassium decline. CONCLUSION: Hyperkalemia is common in emergency situations, especially among patients with altered consciousness. There is a strong positive correlation between the severity of hyperkalemia and mortality risk. CRRT appears to be the most effective potassium reducting strategy, while the use of diuretics should be approached with caution.


Subject(s)
Emergency Service, Hospital , Hyperkalemia , Intensive Care Units , Humans , Hyperkalemia/mortality , Hyperkalemia/therapy , Retrospective Studies , Male , Female , Middle Aged , China/epidemiology , Aged , Potassium/blood , Adult , Severity of Illness Index , Hospital Mortality , ROC Curve , East Asian People
2.
Ren Fail ; 46(2): 2359640, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38832483

ABSTRACT

Research has shown that patients undergoing hemodialysis experience seasonal variations in their serum potassium levels. There was inconsistent seasonal fluctuation in serum potassium levels among the hemodialysis population across different locations. In the form of narrative review for the first time, the article discusses the seasonal changes of serum potassium in this population and its potential reasons, this article demonstrates that it is primarily attributable to seasonal dietary potassium intake. However, existing studies have not quantified seasonal dietary potassium intake, so the results are still speculative. Furthermore, future research ought to further expound upon the clinical implications of seasonal variations in serum potassium levels among dialysis patients, as well as other influencing mechanisms such as the pathophysiological causes of these seasonal changes, particularly those pertaining to dietary, geographical, and regional factors. These findings contribute to a more thorough interpretation of laboratory results in hemodialysis patients and provide important guidance for their individualized dietary management.


Subject(s)
Potassium , Renal Dialysis , Seasons , Humans , Potassium/blood , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/blood , Potassium, Dietary/administration & dosage
3.
Front Endocrinol (Lausanne) ; 15: 1362085, 2024.
Article in English | MEDLINE | ID: mdl-38752174

ABSTRACT

Background: Previous studies have identified several genetic and environmental risk factors for chronic kidney disease (CKD). However, little is known about the relationship between serum metals and CKD risk. Methods: We investigated associations between serum metals levels and CKD risk among 100 medical examiners and 443 CKD patients in the medical center of the First Hospital Affiliated to China Medical University. Serum metal concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS). We analyzed factors influencing CKD, including abnormalities in Creatine and Cystatin C, using univariate and multiple analysis such as Lasso and Logistic regression. Metal levels among CKD patients at different stages were also explored. The study utilized machine learning and Bayesian Kernel Machine Regression (BKMR) to assess associations and predict CKD risk based on serum metals. A chained mediation model was applied to investigate how interventions with different heavy metals influence renal function indicators (creatinine and cystatin C) and their impact on diagnosing and treating renal impairment. Results: Serum potassium (K), sodium (Na), and calcium (Ca) showed positive trends with CKD, while selenium (Se) and molybdenum (Mo) showed negative trends. Metal mixtures had a significant negative effect on CKD when concentrations were all from 30th to 45th percentiles compared to the median, but the opposite was observed for the 55th to 60th percentiles. For example, a change in serum K concentration from the 25th to the 75th percentile was associated with a significant increase in CKD risk of 5.15(1.77,8.53), 13.62(8.91,18.33) and 31.81(14.03,49.58) when other metals were fixed at the 25th, 50th and 75th percentiles, respectively. Conclusions: Cumulative metal exposures, especially double-exposure to serum K and Se may impact CKD risk. Machine learning methods validated the external relevance of the metal factors. Our study highlights the importance of employing diverse methodologies to evaluate health effects of metal mixtures.


Subject(s)
Renal Insufficiency, Chronic , Humans , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/chemically induced , Female , Male , Middle Aged , Models, Theoretical , Adult , Selenium/blood , Risk Factors , China/epidemiology , Metals, Heavy/blood , Metals, Heavy/adverse effects , Aged , Environmental Exposure/adverse effects , Metals/blood , Metals/adverse effects , Machine Learning , Cystatin C/blood , Bayes Theorem , Potassium/blood
4.
Medicine (Baltimore) ; 103(20): e37749, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758907

ABSTRACT

There are multiple mechanisms by which The Coronavirus-19 (COVID-19) infection can cause electrolyte abnormalities, which may not be the case for bacterial causes of pneumonia. This study aimed to assess the differences in electrolyte levels between patients suffering from COVID-19 and bacterial pneumonia. This is an original, retrospective study. Two cohorts of hospitalized patients were included, 1 suffering from COVID-19 and the other from bacterial pneumonia. Their day 1 and day 3 levels of sodium, potassium, magnesium, and phosphorus, as well as their outcomes, were extracted from the charts. Statistical analysis was subsequently performed. Mean admission levels of sodium, potassium, phosphorus, and magnesium were 135.64 ±â€…6.13, 4.38 ±â€…0.69, 3.53 ±â€…0.69, and 2.03 ±â€…0.51, respectively. The mean day 3 levels of these electrolytes were 138.3 ±â€…5.06, 4.18 ±â€…0.59, 3.578 ±â€…0.59, and 2.11 ±â€…0.64, respectively. Patients suffering from bacterial pneumonia were significantly older (N = 219, mean = 64.88 ±â€…15.99) than patients with COVID-19 pneumonia (N = 240, mean = 57.63 ±â€…17.87). Bacterial pneumonia group had significantly higher serum potassium (N = 211, mean = 4.51 ±â€…0.76), and magnesium (N = 115, mean = 2.12 ±â€…0.60) levels compared to COVID-19 group (N = 227, mean = 4.254 ±â€…0.60 for potassium and N = 118, mean = 1.933 ±â€…0.38 for magnesium). Only magnesium was significantly higher among day 3 electrolytes in the bacterial pneumonia group. No significant association between electrolyte levels and outcomes was seen. We found that COVID-19 patients had lower potassium and magnesium levels on admission, possibly due to the effect of COVID-19 on the renin-angiotensin-aldosterone system as well as patient characteristics and management. We did not find enough evidence to recommend using electrolyte levels as a determinator of prognosis, but more research is needed.


Subject(s)
COVID-19 , Hospitalization , Magnesium , Pneumonia, Bacterial , Potassium , Water-Electrolyte Imbalance , Humans , COVID-19/complications , COVID-19/blood , Male , Female , Retrospective Studies , Middle Aged , Aged , Hospitalization/statistics & numerical data , Water-Electrolyte Imbalance/epidemiology , Water-Electrolyte Imbalance/blood , Pneumonia, Bacterial/blood , Pneumonia, Bacterial/complications , Pneumonia, Bacterial/epidemiology , Potassium/blood , Magnesium/blood , SARS-CoV-2 , Electrolytes/blood , Sodium/blood , Phosphorus/blood
5.
BMJ Case Rep ; 17(5)2024 May 09.
Article in English | MEDLINE | ID: mdl-38724210

ABSTRACT

Hyperkalaemia is one of the common electrolyte imbalances dealt with in the emergency department and is caused by extracellular accumulation of potassium ions above normal limits usually greater than 5.0-5.5 mmol/L. It is found in a total of 1-10% of hospitalised patients usually associated with chronic kidney disease and heart failure. The presentation can range from being asymptomatic to deadly arrhythmias. The appearance of symptoms depends on the rate of change rather than just the numerical values. The rare presentation includes periodic paralysis characterised by the sudden onset of short-term muscle weakness, stiffness or paralysis. Management goals are directed towards reducing potassium levels in emergency settings and later on avoiding the triggers for future attacks. In this case, we present a man in his 50s with the generalised weakness later on diagnosed as hyperkalaemic periodic paralysis secondary to tumour lysis syndrome. Emergency physicians dealing with common electrolyte imbalances should keep a sharp eye on their rare presentation and their precipitating factors and should act accordingly.


Subject(s)
Emergency Service, Hospital , Hyperkalemia , Humans , Male , Hyperkalemia/etiology , Hyperkalemia/diagnosis , Hyperkalemia/therapy , Middle Aged , Paralysis, Hyperkalemic Periodic/diagnosis , Paralysis, Hyperkalemic Periodic/complications , Potassium/blood , Potassium/therapeutic use , Diagnosis, Differential , Muscle Weakness/etiology
6.
BMJ Case Rep ; 17(5)2024 May 31.
Article in English | MEDLINE | ID: mdl-38821567

ABSTRACT

While typically thought of as an illicit substance, oxybate salts or gamma-hydroxybutyrate (GHB) has more recently been prescribed to treat narcolepsy by enhancing night-time sleep resulting in decreased daytime drowsiness. This case involves a college-aged female with prescribed GHB for narcolepsy who took her second nightly dose too early. This resulted in mental depression, respiratory failure, intubation and mechanical ventilation. The patient was successfully extubated in the intensive care unit several hours later with no residual morbidity. We were unable to identify any prior reports of mixed-salt oxybate toxicity following mistimed drug administration. This case should serve as a warning to emergency physicians to be on the lookout for GHB as part of the differential diagnosis for patients with narcolepsy presenting with altered mental status. It should also serve as a warning to patients and prescribers that this medication can have outcomes that require immediate medical intervention.


Subject(s)
Drug Overdose , Narcolepsy , Respiration, Artificial , Respiratory Insufficiency , Sodium Oxybate , Humans , Female , Narcolepsy/drug therapy , Narcolepsy/diagnosis , Sodium Oxybate/poisoning , Sodium Oxybate/adverse effects , Respiratory Insufficiency/chemically induced , Respiratory Insufficiency/therapy , Magnesium , Potassium/blood , Potassium/therapeutic use , Medication Errors
7.
Talanta ; 275: 126196, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38705018

ABSTRACT

We have developed an innovative optical emission spectrometry imaging device integrating a diode laser for sample introduction and an atmospheric pressure plasma based on dielectric barrier discharge for atomization and excitation. By optimizing the device parameters and ensuring appropriate leaf moisture, we achieved effective imaging with a lateral resolution as low as 50 µm. This device allows for tracking the accumulation of Cd and related species such as K, Zn, and O2+∙, in plant leaves exposed to different Cd levels and culture times. The results obtained are comparable to established in-lab imaging and quantitative methods. With its features of compact construction, minimal sample preparation, ease of operation, and low limit of detection (0.04 µg/g for Cd), this novel methodology shows promise as an in-situ elemental imaging tool for interdisciplinary applications.


Subject(s)
Atmospheric Pressure , Cadmium , Plant Leaves , Cadmium/analysis , Cadmium/chemistry , Plant Leaves/chemistry , Plasma Gases/chemistry , Zinc/chemistry , Zinc/analysis , Spectrum Analysis/methods , Potassium/analysis , Potassium/blood , Potassium/chemistry
8.
Anal Chim Acta ; 1308: 342661, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38740461

ABSTRACT

BACKGROUND: Timely diagnosis and prevention of diseases require rapid and sensitive detection of biomarkers from blood samples without external interference. Abnormal electrolyte ion levels in the blood are closely linked to various physiological disorders, including hypertension. Therefore, accurate, interference-free, and precise measurement of electrolyte ion concentrations in the blood is particularly important. RESULTS: In this work, a colorimetric sensor based on a biphasic microdroplet extraction is proposed for the detection of electrolyte ions in the blood. This sensor employs mini-pillar arrays to facilitate contact between adjacent blood microdroplets and organic microdroplets serving as sensing phases, with any color changes being monitored through a smartphone's colorimetric software. The sensor is highly resistant to interference and does not require pre-treatment of the blood samples. Remarkably, the sensor exhibits exceptional reliability and stability, allowing for rapid enrichment and detection of K+, Na+, and Cl- in the blood within 10 s (Cl-), 15 s (K+) and 40 s (Na+) respectively. SIGNIFICANCE: The colorimetric sensor based on biphasic microdroplet extraction offers portability due to its compact size and ease of operation without the need for large instruments. Additionally, it is location-independent, making it a promising tool for real-time biomarker detection in body fluids such as blood.


Subject(s)
Colorimetry , Electrolytes , Potassium , Colorimetry/methods , Electrolytes/chemistry , Humans , Potassium/blood , Sodium/blood , Chlorides/blood , Ions/chemistry
9.
PLoS One ; 19(5): e0304479, 2024.
Article in English | MEDLINE | ID: mdl-38820514

ABSTRACT

Although dietary potassium restriction is an acceptable approach to hyperkalemia prevention, it may be insufficient for outpatients with chronic kidney disease (CKD). Most outpatients with CKD use community pharmacies owing to the free access scheme in Japan. The MieYaku-CKD project included a community pharmacist-led nutritional intervention for dietary potassium restriction, with the goal of determining its efficacy for patients' awareness of potassium restriction and serum potassium levels in outpatients with CKD. This was a five-community pharmacy multicenter prospective cohort study with an open-label, before-and-after comparison design. Eligible patients (n = 25) with an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 received nutritional guidance from community pharmacists. The primary outcome was a change in serum potassium levels at 12 weeks post-intervention. The eligible patients' knowledge, awareness, and implementation of potassium restriction were evaluated using a questionnaire. The median value of serum potassium was significantly reduced from 4.7 mEq/L before to 4.4 mEq/L after the intervention [p < 0.001, 95% confidence interval (CI): 0.156-0.500], with no changes in eGFR (p = 0.563, 95% CI: -2.427-2.555) and blood urine nitrogen/serum creatinine ratio (p = 0.904, 95% CI: -1.793-1.214). The value of serum potassium had a tendency of attenuation from 5.3 to 4.6 mEq/L (p = 0.046, 95% CI: 0.272-1.114) in the eGFR < 30 mL/min/1.73 m2 group. A questionnaire revealed that after the intervention, knowledge and attitudes regarding dietary potassium restriction were much greater than before, suggesting that the decrease in serum potassium levels may be related to this nutritional guidance. Our findings indicate that implementing a dietary potassium restriction guidance program in community pharmacies is feasible and may result in lower serum potassium levels in outpatients with CKD.


Subject(s)
Glomerular Filtration Rate , Outpatients , Pharmacists , Potassium , Renal Insufficiency, Chronic , Humans , Female , Male , Renal Insufficiency, Chronic/diet therapy , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/therapy , Prospective Studies , Aged , Potassium/blood , Middle Aged , Japan , Hyperkalemia/prevention & control , Hyperkalemia/blood , Hyperkalemia/diet therapy , Potassium, Dietary/administration & dosage , Aged, 80 and over
10.
Biochem Med (Zagreb) ; 34(2): 020705, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38665867

ABSTRACT

Introduction: This study aimed to examine whether the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) reference intervals for 19 commonly used biochemical assays (potassium, sodium, chloride, calcium, magnesium, inorganic phosphorous, glucose, urea, creatinine, direct and total bilirubin, C-reactive protein (CRP), total protein, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) and lactate dehydrogenase (LD)) could be applied to the newborn population of one Croatian clinical hospital. Materials and methods: Reference interval verification was performed according to the CLSI EP28-A3c guidelines. Samples of healthy newborns were selected using the direct a posteriori sampling method and analyzed on the Beckman Coulter AU680 biochemical analyzer. If verification wasn't satisfactory, further procedure included de novo determination of own reference intervals by analyzing 120 samples of healthy newborns. Results: After the first set of measurements, 14/19 tested reference intervals were adopted for use: calcium, inorganic phosphorous, glucose, urea, creatinine, total bilirubin, CRP, total protein, albumin, AST, ALT, GGT, ALP and LD. A second set of samples was tested for 5 analytes: potassium, sodium, chloride, magnesium and direct bilirubin. The verification results of the additional samples for sodium and chloride were satisfactory, while the results for potassium, magnesium and direct bilirubin remained unsatisfactory and new reference intervals were determined. Conclusions: The CALIPER reference intervals can be implemented into routine laboratory and clinical practice for the tested newborn population for most of the analyzed assays, while own reference intervals for potassium, magnesium and direct bilirubin have been determined.


Subject(s)
Bilirubin , Humans , Infant, Newborn , Reference Values , Croatia , Bilirubin/blood , Male , Female , C-Reactive Protein/analysis , Creatinine/blood , Aspartate Aminotransferases/blood , Alanine Transaminase/blood , Blood Chemical Analysis/standards , gamma-Glutamyltransferase/blood , Alkaline Phosphatase/blood , Potassium/blood , Magnesium/blood , L-Lactate Dehydrogenase/blood , Chlorides/blood , Calcium/blood , Blood Glucose/analysis , Sodium/blood
11.
J Am Heart Assoc ; 13(9): e033236, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38686902

ABSTRACT

BACKGROUND: Both high and low levels of serum potassium measurements are linked with a higher risk of adverse clinical events among patients with type 2 diabetes. The study was aimed at evaluating the implications of the various degrees of initial estimated glomerular filtration rate (eGFR) change on subsequent serum potassium homeostasis following sodium-glucose cotransporter-2 inhibitor (SGLT2i) initiation among patients with type 2 diabetes. METHODS AND RESULTS: We used medical data from a multicenter health care provider in Taiwan and recruited 5529 patients with type 2 diabetes with baseline/follow-up eGFR data available after 4 to 12 weeks of SGLT2i treatment from June 1, 2016, to December 31, 2018. SGLT2i treatment was associated with an initial mean (SEM) eGFR decline of -3.5 (0.2) mL/min per 1.73 m2 in overall study participants. A total of 36.7% (n=2028) of patients experienced no eGFR decline, and 57.9% (n=3201) and 5.4% (n=300) of patients experienced an eGFR decline of 0% to 30% and >30%, respectively. Patients with an initial eGFR decline of >30% were associated with higher variability in consequent serum potassium measurement when compared with those without an initial eGFR decline. Participants with a pronounced eGFR decline of >30% were associated with a higher risk of hyperkalemia ≥5.5 (adjusted hazard ratio,4.59 [95% CI, 2.28-9.26]) or use of potassium binder (adjusted hazard ratio, 2.65 [95% CI, 1.78-3.95]) as well as hypokalemia events <3.0 mmol/L (adjusted hazard ratio, 3.21 [95% CI, 1.90-5.42]) or use of potassium supplement (adjusted hazard ratio, 1.87 [95% CI, 1.37-2.56]) following SGLT2i treatment after multivariate adjustment. CONCLUSIONS: Physicians should be aware that the eGFR trough occurs shortly, and consequent serum potassium changes following SGLT2i initiation.


Subject(s)
Diabetes Mellitus, Type 2 , Glomerular Filtration Rate , Potassium , Sodium-Glucose Transporter 2 Inhibitors , Humans , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Glomerular Filtration Rate/drug effects , Male , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Female , Middle Aged , Potassium/blood , Taiwan/epidemiology , Aged , Risk Factors , Biomarkers/blood , Risk Assessment , Hyperkalemia/chemically induced , Hyperkalemia/blood , Hyperkalemia/epidemiology , Kidney/physiopathology , Kidney/drug effects , Retrospective Studies , Hypokalemia/chemically induced , Hypokalemia/blood , Hypokalemia/epidemiology , Time Factors , Treatment Outcome , Diabetic Nephropathies/blood , Diabetic Nephropathies/diagnosis
14.
J Emerg Med ; 66(4): e421-e431, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38462394

ABSTRACT

BACKGROUND: Hyperkalemia is a common electrolyte abnormality that requires urgent treatment. Insulin is an effective treatment for hyperkalemia, but risk factors for developing insulin-induced hypoglycemia exist (e.g., low pretreatment glucose or renal impairment). OBJECTIVE: This study evaluated the impact of a hyperkalemia protocol tailored to glucose concentration and renal function on insulin-induced hypoglycemia. METHODS: This was a retrospective cohort study of emergency department patients with glucose ≤ 100 mg/dL treated with insulin for hyperkalemia. The primary outcome was incidence of hypoglycemia in patients treated prior to (July 1, 2018-June 30, 2019) vs. after (January 1, 2020-December 31, 2020) the protocol update, which individualized insulin and dextrose doses by glucose concentration and renal function. Secondary outcomes included change in potassium and protocol safety. We assessed factors associated with hypoglycemia using multiple logistic regression. RESULTS: We included 202 total patients (preimplementation: 114, postimplementation: 88). Initial insulin dose was lower in the postimplementation group (p < 0.001). We found a nonsignificant reduction in hypoglycemia in the postimplementation group (42.1% vs. 30.7%, p = 0.10). Degree of potassium reduction was similar in patients who received insulin 5 units vs. 10 units (p = 0.72). Higher pretreatment glucose (log odds ratio [OR] -0.05, 95% confidence interval [CI] -0.08 to -0.02) and additional insulin administration (log OR -1.55, 95% CI -3.01 to -0.25) were associated with reduced risk of developing hypoglycemia. CONCLUSION: A hyperkalemia protocol update was not associated with a significant reduction in hypoglycemia, and the incidence of hypoglycemia remained higher than anticipated. Future studies attempting to optimize treatment in this high-risk population are warranted.


Subject(s)
Hyperkalemia , Hypoglycemia , Insulin , Humans , Blood Glucose/analysis , Glucose/analysis , Hyperkalemia/drug therapy , Hypoglycemia/drug therapy , Hypoglycemia/chemically induced , Insulin/adverse effects , Kidney , Potassium/blood , Retrospective Studies
15.
Clin Pharmacokinet ; 63(4): 551-560, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38504082

ABSTRACT

BACKGROUND: Sodium zirconium cyclosilicate (SZC) is an approved oral treatment for hyperkalemia that selectively binds potassium (K+) in the gastrointestinal tract and removes K+ from the body through increased fecal excretion. Here, we describe the population pharmacodynamic (PopPD) response of serum K+ concentration in patients with hyperkalemia who are treated with SZC, estimate the impact of patients' intrinsic and extrinsic factors, and compare predicted serum K+ responses between 5 g alternate daily (QOD) and 2.5 g once daily (QD) maintenance doses. METHODS: PopPD analysis was based on pooled data from seven phase II and III clinical trials for SZC. A semi-mechanistic longitudinal mixed-effects (base) model was used to characterize serum K+ concentration after SZC dosing. Indirect-response, virtual pharmacokinetics-pharmacodynamics (PK-PD) modeling was used to mimic the drug exposure compartment. Full covariate modeling was used to assess covariate impact on the half-maximal effective concentration of drug (EC50), placebo response, and Kout. Models were evaluated using goodness-of-fit plots, relative standard errors, and visual predictive checks, and data were stratified to optimize model performance across subgroups. Covariate effects were evaluated based on the magnitude of change in serum K+ between baseline and end of correction phase dosing (48 h, SZC 10 g three times a day) and maintenance phase dosing (28 days, SZC 10 g QD) using a reference subject. RESULTS: The analysis data set included 2369 patients and 25,764 serum K+ observations. The mean (standard deviation) patient age was 66.0 (12) years, 61% were male, 68% were White, 34% had congestive heart failure, and 62% had diabetes. Mean (standard deviation) serum K+ at baseline was 5.49 (0.43) mmol/L. Both the base and full covariance models adequately described observed data. In the final model, there was a sigmoid exposure response on Kin, with EC50 of 32.8 g and a Hill coefficient of 1.36. The predicted placebo-adjusted dose-responses of serum K+ change appeared nearly linear in the correction and maintenance phases. No clinically meaningful difference in placebo-adjusted serum K+ change from baseline at 28 days was observed between maintenance regimens of SZC 5 g QOD and 2.5 g QD. A greater SZC treatment response was associated with high serum K+ at baseline, advanced age, lower body weight, lower estimated glomerular filtration rate, and Black/African American and Asian race, compared with the reference patient. The impact of heart failure status and diabetes status was only minor. CONCLUSIONS: The PopPD model of SZC adequately described changes in serum K+ concentration during correction and maintenance phase dosing. A greater treatment response was associated with various covariates, but the impact of each was modest. Overall, these findings suggest that no adjustment in SZC dose is needed for any of the covariates evaluated.


Subject(s)
Dose-Response Relationship, Drug , Hyperkalemia , Models, Biological , Potassium , Silicates , Adult , Aged , Female , Humans , Male , Middle Aged , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic , Hyperkalemia/blood , Hyperkalemia/drug therapy , Potassium/blood , Silicates/administration & dosage , Silicates/pharmacokinetics
16.
Clin Pharmacol Ther ; 115(6): 1408-1417, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38425181

ABSTRACT

Thiazide diuretics, widely used in hypertension, cause a variety of adverse reactions, including hyperglycemia, hyperuricemia, and electrolyte abnormalities. In this study, we aimed to identify genetic variants that interact with thiazide-use to increase the risk of these adverse reactions. Using UK Biobank data, we first performed genomewide variance quantitative trait locus (vQTL) analysis of ~ 6.2 million SNPs on 95,493 unrelated hypertensive White British participants (24,313 on self-reported bendroflumethiazide treatment at recruitment) for 2 blood (glucose and urate) and 2 urine (potassium and sodium) biomarkers. Second, we conducted direct gene-environment interaction (GEI) tests on the significant (P < 2.5 × 10-9) vQTLs, included a second UK Biobank cohort comprising 13,647 unrelated hypertensive White British participants (3,478 on thiazides other than bendroflumethiazide) and set significance at P = 0.05 divided by the number of vQTL SNPs tested for GEIs. The vQTL analysis identified eight statistically significant SNPs for blood glucose (5 SNPs) and serum urate (3 SNPs), with none being identified for the urinary biomarkers. Two of the SNPs (1 glucose SNP: CDKAL1 intron rs35612982, GEI P = 6.24 × 10-3; and 1 serum urate SNP: SLC2A9 intron rs938564, GEI P = 4.51 × 10-4) demonstrated significant GEI effects in the first, but not the second, cohort. Both genes are biologically plausible candidates, with the SLC2A9-mediated interaction having been previously reported. In conclusion, we used a two-stage approach to detect two biologically plausible genetic loci that can interact with thiazides to increase the risk of thiazide-associated biochemical abnormalities. Understanding how environmental exposures (including medications such as thiazides) and genetics interact, is an important step toward precision medicine and improved patient outcomes.


Subject(s)
Biological Specimen Banks , Genome-Wide Association Study , Hyperglycemia , Hyperuricemia , Polymorphism, Single Nucleotide , Sodium Chloride Symporter Inhibitors , Humans , United Kingdom/epidemiology , Female , Hyperuricemia/genetics , Hyperuricemia/urine , Hyperuricemia/chemically induced , Male , Middle Aged , Hyperglycemia/genetics , Hyperglycemia/chemically induced , Hyperglycemia/urine , Hyperglycemia/epidemiology , Aged , Sodium Chloride Symporter Inhibitors/adverse effects , Uric Acid/urine , Uric Acid/blood , Quantitative Trait Loci , Gene-Environment Interaction , Hypertension/genetics , Hypertension/chemically induced , Blood Glucose/drug effects , Blood Glucose/metabolism , Potassium/urine , Potassium/blood , Sodium/urine , Adult , Biomarkers/urine , Biomarkers/blood , UK Biobank
17.
Am J Clin Nutr ; 119(5): 1155-1163, 2024 May.
Article in English | MEDLINE | ID: mdl-38432485

ABSTRACT

BACKGROUND: Although the subject of numerous studies, the associations between dietary sodium, potassium, and the ratio of dietary sodium to potassium with blood pressure are not clear-cut. In addition, there is a paucity of research on these relationships in prospective cohort studies with representation from diverse Hispanic/Latino adults. OBJECTIVES: To evaluate the associations between dietary intake of sodium, potassium, and the ratio of dietary sodium to potassium and blood pressure in a diverse sample of Hispanics living in the United States. METHODS: This analysis included 11,429 Hispanic/Latino participants of the prospective cohort Hispanic Community Health Study/Study of Latinos recruited between 2008 and 2011 in visit 1 who participated in a follow-up visit in 2014-2017. Dietary sodium and potassium intakes were averaged from 2 interviewer-administered 24-h diet recalls collected at visit 1. At both visits, blood pressure was measured 3 times in a seated position and averaged. We assessed the relationship between dietary sodium, potassium, and the sodium-to-potassium ratio with changes in systolic and diastolic blood pressure using survey-weighted multivariable-adjusted regression models. RESULTS: At visit 1, the mean age was 41 y, and the mean sodium intake was 3203 mg/d. Each 500 mg/d sodium increment in intake was associated with an increase in systolic blood pressure (ß: 0.35 [mmHg]; 95% confidence interval: 0.06, 0.63) and diastolic blood pressure (ß: 0.45 [mmHg]; 95% confidence interval: 0.08, 0.82). Dietary potassium and the molar ratio of dietary sodium to potassium were not associated with changes in systolic or diastolic blood pressure. CONCLUSIONS: Among a large sample of diverse United States Hispanic/Latino adults, higher sodium intake was associated with small increases in systolic blood pressure over 6 y. This research underscores the importance of dietary sodium reduction in maintaining lower blood pressure.


Subject(s)
Blood Pressure , Hispanic or Latino , Potassium, Dietary , Sodium, Dietary , Humans , Female , Male , Prospective Studies , Sodium, Dietary/administration & dosage , Adult , Middle Aged , Potassium, Dietary/administration & dosage , United States , Cohort Studies , Potassium/blood
18.
Nutr Hosp ; 41(2): 326-329, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38328927

ABSTRACT

Introduction: Introduction: we report two cases with severe hypokalemia. Patients and methods: a 68-year-old woman was admitted with lower limb swelling and urinary symptoms; on the fourth day serum K+ concentration (s[K+]) was 2.3 mmol/L. A 64-year-old woman was admitted with pain in the lumbosacral spine, she was diagnosed with multiple myeloma. After receiving specific therapy she showed s[K+] at 2.4 mmol/L. A KCl solution containing 26.8 mEq of K+ was administered enterally, which increased s[K+] by 0.7 mmol/L within 1 h. Results and conclusion: these cases reveal that peak s[K+] may be achieved within 1 hour after KCl intake in severe hypokalemia, which is probably faster than IV administration.


Introducción: Introducción: se presentan dos casos clínicos con hipopotasemia severa. Pacientes y métodos: mujer de 68 años que ingresó por edema en miembros inferiores y síntomas urinarios; al cuarto día, el nivel sérico de K+ ([K+]s) era de 2,3 mmol/L. Una mujer de 64 años ingresó por dolor en la columna lumbosacra y fue diagnosticada de mieloma múltiple; luego de recibir terapia específica, presentó una [K+]s de 2.4 mmol/L. Se administró por vía enteral una solución de KCl que contenía 26,8 mEq de K+, aumentando la [K+]s en 0,7 mmol/L en 1 h. Resultados y conclusión: estos casos revelan que la [K+]s máxima se alcanzaría 1 hora después de la ingestión de KCl en la hipopotasemia grave, probablemente en menos tiempo que por vía intravenosa.


Subject(s)
Hypokalemia , Potassium , Humans , Female , Hypokalemia/therapy , Hypokalemia/etiology , Aged , Middle Aged , Potassium/blood , Potassium Chloride/administration & dosage , Potassium Chloride/therapeutic use , Enteral Nutrition/methods
19.
J Appl Lab Med ; 9(3): 558-564, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38300631

ABSTRACT

BACKGROUND: Hemolysis is a common reason for specimen rejection in the laboratory. Our experience suggested that hemolysis (H) flag limits are too strict for some analytes leading to unnecessary specimen rejections. This study summarizes H flags for commonly rejected analytes on the Beckman Coulter DxC 700 AU analyzer. METHODS: We evaluated analytes with low-limit H flags and high rejection rates. These included: aspartate aminotransferase (AST), alanine aminotransferase (ALT), iron (IRN), potassium (K), direct bilirubin (DBIL), magnesium (Mg), amylase (AMY), sodium (Na), gamma-glutamyltransferase (GGT), phosphorus (PHOS), albumin (ALB), alkaline phosphatase (ALKP), and lactate dehydrogenase (LDH). Five patient plasma pools without hemolysis were made from 50 patient specimens. Neat pools were analyzed to establish baseline analyte concentrations. A hemolysate was created by diluting whole blood with distilled water. Each analyte was tested after spiking each pool with the hemolysate to specific hemoglobin concentrations corresponding to manufacturer's H flags. Percent differences were calculated between baseline pool means and each flag's pool mean. Acceptance limits were based upon the average of the 2019 CLIA and the method precision limits. Calculated percent differences greater than the acceptance limits were considered significant. RESULTS: Manufacturer-defined hemolysis flags can be updated to greater than 1+ for Na, K, and AST, greater than 3+ for ALKP, and greater than 4+ for AMY and Mg. No changes were noted for the remaining analytes. CONCLUSIONS: The hemolysis criteria set for ALKP, AMY, AST, Mg, K, and Na were updated in the Remisol Advance middleware, which led to a 56% reduction in rejected hemolyzed specimens.


Subject(s)
Hemolysis , Humans , Bilirubin/blood , Blood Chemical Analysis/methods , Blood Chemical Analysis/instrumentation , Blood Chemical Analysis/standards , Aspartate Aminotransferases/blood , Alanine Transaminase/blood , Potassium/blood , Iron/blood , Sodium/blood
20.
Nephrology (Carlton) ; 29(6): 311-324, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38403867

ABSTRACT

Hyperkalaemia is an electrolyte imbalance that impairs muscle function and myocardial excitability, and can potentially lead to fatal arrhythmias and sudden cardiac death. The prevalence of hyperkalaemia is estimated to be 6%-7% worldwide and 7%-10% in Asia. Hyperkalaemia frequently affects patients with chronic kidney disease, heart failure, and diabetes mellitus, particularly those receiving treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors. Both hyperkalaemia and interruption of RAAS inhibitor therapy are associated with increased risks for cardiovascular events, hospitalisations, and death, highlighting a clinical dilemma in high-risk patients. Conventional potassium-binding resins are widely used for the treatment of hyperkalaemia; however, caveats such as the unpalatable taste and the risk of gastrointestinal side effects limit their chronic use. Recent evidence suggests that, with a rapid onset of action and improved gastrointestinal tolerability, novel oral potassium binders (e.g., patiromer and sodium zirconium cyclosilicate) are alternative treatment options for both acute and chronic hyperkalaemia. To optimise the care for patients with hyperkalaemia in the Asia-Pacific region, a multidisciplinary expert panel was convened to review published literature, share clinical experiences, and ultimately formulate 25 consensus statements, covering three clinical areas: (i) risk factors of hyperkalaemia and risk stratification in susceptible patients; (ii) prevention of hyperkalaemia for at-risk individuals; and (iii) correction of hyperkalaemia for at-risk individuals with cardiorenal disease. These statements were expected to serve as useful guidance in the management of hyperkalaemia for health care providers in the region.


Subject(s)
Consensus , Hyperkalemia , Humans , Hyperkalemia/epidemiology , Hyperkalemia/therapy , Hyperkalemia/diagnosis , Asia/epidemiology , Risk Factors , Potassium/blood , Silicates/therapeutic use , Silicates/adverse effects
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