CLSI-based verification and de novo establishment of reference intervals for common biochemical assays in Croatian newborns.

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.

Population Pharmacodynamic Dose-Response Analysis of Serum Potassium Following Dosing with Sodium Zirconium Cyclosilicate.

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.

Impact of a Hyperkalemia Protocol Tailored to Glucose Concentration and Renal Function on Insulin-Induced Hypoglycemia in Patients with Low Pretreatment Glucose.

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.

Maximum serum K+ concentration within 1 hour with enteral replacement in severe hypokalemia.

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.

Rationale, Design, and Patient Characteristics of a Cluster-Randomized Pragmatic Trial to Improve Mineralocorticoid Antagonist Use.

BACKGROUND: Despite robust evidence and strong guideline recommendations supporting use of mineralocorticoid receptor antagonists (MRAs) to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF), these medications remain underused in clinical practice. OBJECTIVES: The goal is to determine if providing a tailored best practice alert (BPA) to outpatient providers suggesting guideline-recommended MRAs or information about available hyperkalemia treatment, if present, for patients with HFrEF will increase short-term MRA prescriptions. METHODS: PROMPT-MRA (Pragmatic Trial of Messaging to Providers About Treatment With Mineralocorticoid Receptor Antagonists) is a pragmatic, cluster-randomized, controlled study. A total of 119 providers were randomized to receive a BPA or usual care. During an outpatient visit with participating providers, the BPA displayed recent laboratory test values and ejection fraction. The alert suggested guideline-recommended MRAs for eligible patients with a serum potassium of <5.0 mEq/L or novel potassium binders for those with a serum potassium of ≥5.0 mEq/L, each linked to an order set containing the corresponding medication and laboratory monitoring. RESULTS: PROMPT-MRA completed enrollment with 1,210 patients. The primary outcome of PROMPT-MRA is to determine if a tailored BPA for outpatients with HFrEF will lead to higher MRA prescriptions 6 months following randomization compared with usual care. Secondary outcomes included incidence of hyperkalemia, use of novel potassium binders, heart failure hospitalizations, and mortality. CONCLUSIONS: If effective, the BPA can be scaled to improve population health outcomes with increased MRA prescribing among eligible patients with HFrEF, with or without a history of hyperkalemia. (Pragmatic Trial of Alerts for Use of Mineralocorticoid Receptor Antagonists [PROMPT-MRA]; NCT04903717).

Potassium levels in women with polycystic ovary syndrome using spironolactone for long-term.

OBJECTIVE: Spironolactone (SPL) has been used to manage hyperandrogenic manifestations in women with polycystic ovary syndrome (PCOS), but data on the risk of hyperkalemia in this population are scarce. The aim of this study was to evaluate the incidence of hyperkalemia in women with PCOS using SPL in the long term. DESIGN: Single-centre retrospective study. PATIENTS: Inclusion and analysis of 98 treatment periods in 78 women with PCOS (20 of whom were duplicates, returning after treatment interruption for a mean of 38 months) who received SPL for a minimum of 12 months and had at least three measurements of potassium levels over time. MEASUREMENTS: Clinical and hormonal profiles before and during SPL treatment. RESULTS: Mean age was 29.1 (SD: 9.6) years, and body mass index was 32.2 (SD: 8.1) kg/m². Nine patients had diabetes, and 22 had prediabetes. SPL was used in combination with combined oral contraceptive pills in 55 participants and progestin-only pills/long-acting reversible contraception in 28; metformin was added in 35, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in 15. Median SPL dose was 100 (range: 50-150) mg. A total of 327 serum potassium measurements were obtained (84 pre-exposure and 243 postexposure). Four potassium measurements were above the reference range before exposure and 19 during exposure. All potassium measurements above the reference range during follow-up were classified as mild hyperkalemia (5.1-5.5 mEq/L). CONCLUSIONS: The present findings suggest that women with PCOS, without kidney or heart disease, using SPL combined with hormonal contraception for managing clinical hyperandrogenism have a low incidence of hyperkalemia and well-tolerated minor adverse effects.

A Retrospective Analysis of Intravenous Insulin versus Insulin and Nebulized Albuterol for the Treatment of Hyperkalemia in the Emergency Department.

There is limited literature evaluating the use of nebulized albuterol in the management of hyperkalemia. The objective was to evaluate the efficacy of insulin alone compared with the addition of nebulized albuterol for the treatment of hyperkalemia. This is a retrospective, single-center evaluation of adult patients with hyperkalemia attending the Emergency Department of a large urban academic medical center. Consecutive patients with a potassium level of >5 mmol/L were included. Patients without a repeat potassium level within 4 hours of medication administration, those receiving hemodialysis before a repeat serum potassium, or those that had a hemolyzed blood sample were excluded. The primary outcome was the change in potassium level within 4 hours in patients who received insulin monotherapy versus patients who received insulin and albuterol. The secondary outcomes included hospital length of stay, intensive care unit (ICU) admission, and mortality. Out of the 204 patients, 141 received insulin, whereas 63 received insulin and nebulized albuterol. There was no difference in the change in potassium level between the insulin and the insulin and nebulized albuterol groups (0.85 ± 0.6 vs 0.96 ± 0.78 mmol/L; P = .36). There was no difference in median hospital length of stay (8.6 days, IQR 13.2 days, vs 5.6 days, IQR 8.2 days; P = .09), ICU admission (31.9% vs 38.1%; P = .39), and all-cause mortality (14.9% vs 17.5%; P = .64). In this retrospective analysis, the addition of albuterol to insulin for the treatment of hyperkalemia did not result in a greater change in potassium level within 4 hours of therapy.

DIALIZE China: A Phase IIIb, Randomized, Placebo-Controlled Study to Reduce Predialysis Hyperkalemia With Sodium Zirconium Cyclosilicate in Chinese Patients.

PURPOSE: The DIALIZE China study (Reduce Incidence of Pre-Dialysis Hyperkalaemia With Sodium Zirconium Cyclosilicate in Chinese Subjects) (NCT04217590) evaluated sodium zirconium cyclosilicate (SZC) for the management of hyperkalemia in Chinese patients undergoing hemodialysis. METHODS: In the double-blind, Phase IIIb DIALIZE China study, Chinese adults with kidney failure and predialysis hyperkalemia (predialysis serum potassium [sK+] concentration >5.4 mmol/L after the long interdialytic interval [LIDI] and >5.0 mmol/L after ≥1 short interdialytic interval) who were receiving hemodialysis 3 times weekly were randomized to placebo or SZC 5 g once daily on nondialysis days. Doses were titrated towards maintaining normokalemia for 4 weeks (titration period) in 5-g increments up to 15 g. Primary efficacy was the proportion of responders during the 4-week evaluation period following the titration period (ie, those with a predialysis sK+ of 4.0-5.0 mmol/L for at least 3 of 4 hemodialysis visits following the LIDI) who did not require urgent rescue therapy. FINDINGS: Overall, 134 adults (mean [SD] age, 55 [11.3] years) were randomized to SZC or placebo (n = 67 each). There were significantly more responders with SZC (37.3%) versus placebo (10.4%; estimated odds ratio [OR] = 5.10; 95% CI, 1.90-15.12; P < 0.001). The probability of all predialysis sK+ concentrations being 3.5 to 5.5 mmol/L was significantly higher with SZC versus placebo (estimated OR = 6.41; 95% CI, 2.71-15.12; P < 0.001). A greater proportion of patients achieved an sK+ of 3.5 to 5.5 mmol/L on at least 3 of 4 LIDI visits during evaluation with SZC (73.1%) versus placebo (29.9%). Serious adverse events occurred in 9.1% and 11.9% of patients in the SZC and placebo groups, respectively. IMPLICATIONS: SZC treatment for predialysis hyperkalemia is effective and well tolerated in Chinese patients with kidney failure receiving hemodialysis. CLINICALTRIALS: gov identifier: NCT04217590.

High facility-level serum potassium variability associated with mortality in hemodialysis patients: results from Chinese Dialysis Outcomes and Practice Patterns Study (DOPPS).

The role of facility-level serum potassium (sK+) variability (FL-SPV) in dialysis patients has not been extensively studied. This study aimed to evaluate the association between FL-SPV and clinical outcomes in hemodialysis patients using data from the China Dialysis Outcomes and Practice Patterns Study (DOPPS) 5. FL-SPV was defined as the standard deviation (SD) of baseline sK+ of all patients in each dialysis center. The mean and SD values of FL-SPV of all participants were calculated, and patients were divided into the high FL-SPV (>the mean value) and low FL-SPV (≤the mean value) groups. Totally, 1339 patients were included, with a mean FL-SPV of 0.800 mmol/L. Twenty-three centers with 656 patients were in the low FL-SPV group, and 22 centers with 683 patients were in the high FL-SPV group. Multivariate logistic regression analysis showed that liver cirrhosis (OR = 4.682, 95% CI: 1.246-17.593), baseline sK+ (<3.5 vs. 3.5 ≤ sK+ < 5.5 mmol/L, OR = 2.394, 95% CI: 1.095-5.234; ≥5.5 vs. 3.5 ≤ sK+ < 5.5 mmol/L, OR = 1.451, 95% CI: 1.087-1.939), dialysis <3 times/week (OR = 1.472, 95% CI: 1.073-2.020), facility patients' number (OR = 1.088, 95% CI: 1.058-1.119), serum HCO3- level (OR = 0.952, 95% CI: 0.921-0.984), dialysis vintage (OR = 0.919, 95% CI: 0.888-0.950), other cardiovascular disease (OR = 0.508, 95% CI: 0.369-0.700), and using high-flux dialyzer (OR = 0.425, 95% CI: 0.250-0.724) were independently associated with high FL-SPV (all p < .05). After adjusting potential confounders, high FL-SPV was an independent risk factor for all-cause death (HR = 1.420, 95% CI: 1.044-1.933) and cardiovascular death (HR = 1.827, 95% CI: 1.188-2.810). Enhancing the management of sK+ of hemodialysis patients and reducing FL-SPV may improve patient survival.

Mediation of serum albumin in the association of serum potassium with mortality in Chinese dialysis patients: a prospective cohort study.

BACKGROUND: The clinical importance of hypokalemia is likely underrecognized in Chinese dialysis patients, and whether its clinical effect was mediated by serum albumin is not fully elucidated. This study aimed to explore the association between serum potassium and mortality in dialysis patients of a Chinese nationwide multicenter cohort, taking albumin as a consideration. METHODS: This was a prospective nation-wide multicenter cohort study. Restricted cubic splines were used to test the linearity of serum potassium and relationships with all-cause (AC) and cardiovascular (CV) mortality and a subsequent two-line piecewise linear model was fitted to approach the nadir. A mediation analysis was performed to examine relations of albumin to potassium and mortalities. RESULTS: A total of 10,027 patients were included, of whom 6605 were peritoneal dialysis and 3422 were hemodialysis patients. In the overall population, the mean age was 51.7 ±â€Š14.8 years, 55.3%(5546/10,027) were male, and the median dialysis vintage was 13.60 (4.70, 39.70) months. Baseline serum potassium was 4.30 ±â€Š0.88 mmol/L. After a median follow-up period of 26.87 (14.77, 41.50) months, a U-shape was found between potassium and mortality, and a marked increase in risk at lower potassium but a moderate elevation in risk at higher potassium were observed. The nadir for AC mortality risk was estimated from piecewise linear models to be a potassium concentration of 4.0 mmol/L. Interestingly, the significance of the association between potassium and mortality was attenuated when albumin was introduced into the extended adjusted model. A subsequent significant mediation by albumin for potassium and AC and CV mortalities were found ( P < 0.001 for both), indicating that hypokalemia led to higher mortality mediated by low serum albumin, which was a surrogate of poor nutritional status and inflammation. CONCLUSIONS: Associations between potassium and mortalities were U-shaped in the overall population. The nadir for AC mortality risk was at a potassium of 4.0 mmol/L. Serum albumin mediated the association between potassium and AC and CV mortalities.

Targeted potassium levels to decrease arrhythmia burden in high risk patients with cardiovascular diseases (POTCAST): Study protocol for a randomized controlled trial.

BACKGROUND: Low plasma potassium (p-K) is associated with increased risk of malignant arrhythmia and observational studies indicate protective effects of p-K in the upper reference level. However, randomized clinical studies are needed to document whether actively increasing p-K to high-normal levels is possible and safe and improves cardiovascular outcomes. OBJECTIVE: To investigate if increased p-K reduces the risk of malignant arrhythmia and all-cause death in high-risk patients with a cardiovascular disease treated with an implantable cardioverter defibrillator (ICD) for primary or secondary preventive causes. Secondly, to investigate whether high-normal p-K levels can be safely reached and maintained using already available medications and potassium-rich dietary guidance. METHODS: This is a prospective, randomized, and open-labelled study enrolling patient at high-risk of malignant arrhythmias. According to sample size calculations, 1,000 patients will be randomized 1:1 to either an investigational regiment that aims to increase and maintain p-K at high-normal levels (4.5-5.0 mmol/L) or to usual standard of care and followed for an expected four years. The trial will run until a total of 291 events have occurred providing an α = 0.05 and 1-ß = 0.80. The composite primary endpoint includes ventricular tachycardia >125 bpm lasting >30 seconds, any appropriate ICD-therapy, and all-cause mortality. At present, 739 patients have been randomized. CONCLUSIONS: We present the rationale for the design of the POTCAST trial. The inclusion was initiated 2019 and is expected to be finished 2022. The study will show if easily available treatments to increase p-K may be a new treatment modality to protect against malignant arrythmias.

Short-term Effects of Losartan on Cardiovascular Risk and Allograft Injury Biomarkers in Kidney Transplant Recipients.

BACKGROUND: There is a controversy over the renoprotective and cardioprotective effects of renin-angiotensin-aldosterone system blockade in kidney transplant recipients (KTRs). The aim of the study was to evaluate the short-term effects of losartan on allograft injury, cardiovascular risk biomarkers and safety of the treatment in KTRs. METHODS: An interim analysis of a prospective, open, multicenter, controlled clinical trial CELART (Cardiovascular Effects of Losartan After Renal Transplantation) was performed. KTRs were allocated to losartan (L) 50 to 100 mg or standard hypotensive treatment (ST) group to reach target blood pressure (BP) <140/90 mm Hg. The short-term effects of the therapy were evaluated after 6 months: estimated glomerular filtration rate (eGFR), albuminuria, the intrarenal fibrosis biomarkers: urine excretion of transforming growth factor ß-1 (TGFß-1) and procollagen type III amino terminal propeptide (PIIINP), cardiac biomarker: serum concentration of N-terminal-pro-B-type natriuretic peptide (NT-proBNP), 24-hour ambulatory BP measurement, and hemoglobin and potassium concentrations. RESULTS: At baseline the groups did not differ with respect to age, primary nephropathy, comorbidity, immunosuppressive therapy, albuminuria, and graft function. A total of 61 (L group) and 73 (ST group) patients reached the target BP and completed protocol at 6 months. After 6 months of therapy there were no significant differences in changes of eGFR, albuminuria, hemoglobin and potassium concentrations, urine excretion of PIIINP, and TGFß-1 between groups. There was a trend in the L group to decrease the concentration of serum NT-proBNP. CONCLUSIONS: Losartan shows minimal adverse effects and no influence on graft function and biomarkers of graft fibrosis. It may have a positive effect on cardiovascular risk in KTRs. Further interim analyses of the CELART study will be conducted.

Potassium responses to sodium zirconium cyclosilicate in hyperkalemic hemodialysis patients: post-hoc analysis of DIALIZE.

BACKGROUND: Sodium zirconium cyclosilicate (SZC) is an effective and well-tolerated treatment for hyperkalemia in maintenance hemodialysis patients. In post-hoc analyses of the phase 3b DIALIZE study, we examined the spectrum of potassium responses to SZC. METHODS: Post-hoc analyses with SZC and placebo included: the number of long interdialytic interval (LIDI) visits during the 4-week evaluation period where patients attained pre-dialysis serum potassium (sK+) concentrations of 4.0-5.0 and 4.0-5.5 mmol/L; potassium gradient (the difference between pre-dialysis sK+ and dialysate potassium) at days 36, 43, 50, and 57, and change from baseline to the end of treatment (EOT) using categories of potassium gradient (1 to < 2, 2 to < 3, 3 to < 4, and ≥ 4 mmol/L). RESULTS: A greater proportion of patients achieved the ranges of pre-dialysis sK+ concentration with SZC versus placebo for ≥1, ≥ 2, ≥ 3, and 4 LIDI visits over 4 weeks; 23.7 and 48.5% of patients in the SZC group achieved pre-dialysis sK+ concentrations of 4.0-5.0 and 4.0-5.5 mmol/L, respectively, at all 4 LIDI visits. Baseline mean potassium gradient was similar with SZC and placebo. At day 57, mean (standard deviation) potassium gradient was 2.78 (0.08) mmol/L with SZC and 3.52 (0.08) mmol/L with placebo; mean difference (95% confidence interval) was - 0.74 mmol/L (- 0.97 to - 0.52). A greater reduction in potassium gradient category from baseline towards lower-risk categories at EOT was observed with SZC versus placebo. CONCLUSIONS: These analyses expand our knowledge of the spectrum of potassium responses with SZC in hyperkalemic hemodialysis patients. TRIAL REGISTRATION: NCT03303521 .

Hyperkalemia in chronic peritoneal dialysis patients.

Background. Chronic peritoneal dialysis (PD) patients often develop hypokalemia but less commonly hyperkalemia.Methods. We explored incidence and mechanisms of hyperkalemia in 779 serum samples from 33 patients on PD for 1 - 59 months. Normal serum potassium concentration was defined as 3.5 - 5.1 meq/l.Results. Mean monthly serum potassium concentrations were normal (except for 1 month), but we observed hypokalemia (<3.5 meq/l) in 5% and hyperkalemia (>5.1 meq/l) in 14% of 779 serum samples. Incidence of hyperkalemia did not change over time on PD: Year 1 (15%), Year 2 (11%), Year 3 (19%), Years 4-5 (22%). Hyperkalemia was mostly modest but occasionally extreme [5.2-5.4 meq/l (55%), 5.5-5.7 meq/l (21%), 5.8-6.0 meq/l (10%), >6.0 meq/l (14%)]. Of 31 patients (2 excluded due to brief PD time), 39% displayed hyperkalemia only, 23% displayed hypokalemia only, and the remainder (38%) displayed both or neither. Comparing hypokalemia-only with hyperkalemia-only patients, we found no difference in potassium chloride therapy, medications interrupting the renin-angiotensin system, small-molecule transport status, and renal urea clearance. We compared biochemical parameters from the hypokalemic and hyperkalemic serum samples and observed lower bicarbonate concentrations, higher creatinine concentrations, and higher urea nitrogen concentrations in the hyperkalemic samples (p < 0.001 for each), without difference in glucose concentrations.Conclusion. We observed hyperkalemia 3 times as frequently as hypokalemia in our PD population. High-potassium diet, PD noncompliance, increased muscle mass, potassium shifts, and/or the daytime period without PD might contribute to hyperkalemia.

The Predictor Potential Role of the Glucose to Potassium Ratio in the Diagnostic Differentiation of Massive and Non-Massive Pulmonary Embolism.

OBJECTIVE: Acute pulmonary embolism (PE) is one of the main causes of death and has a course as massive (MPE) or non-massive (NMPE). The study investigates the indicator potential of Glucose to Potassium ratio (GPR) in the differential diagnosis of MPE and NMPE. MATERIALS AND METHODS: The study was designed as a retrospective cross-sectional clinical cohort in patients with PE. A total of 111 participants enrolled in the research separating two groups: MPE (n:54) and NMPE (n:67). The GPR was calculated by dividing serum glucose by potassium levels and its results were compared with D-Dimer, Pulmonary Artery Pressure (PAP), and C-Reactive Protein Test (CRP). RESULTS: D-Dimer was measured as 6.5 ± 5.7 µg/L in the MPE and found higher than the NMPE (3.9 ± 5.2 µg/L) (P = .019). CRP (100 ± 83.5 to 30.9 ± 42.7 mg/L; P = .0001) and PAP (49.5 ± 11.9 to 34.8 ± 7.3 mmHg; P = .0001) were found increased in the MPE. GPR strongly increased in the MPE (30.7 ± 7.5 to 24.9 ± 4.3; P = .0003) in line with CRP, D-Dimer and PAP. GPR showed a stronger diagnostic value (AUC: 0.733; P = .00001; Sensitivity:72%; Spesifity:70%; Cut-off: 26.5). PAP and GPR showed significant efficiency on occurrence of the MPE according to the binary logistic regression. CONCLUSION: The GPR, as a novel and cheap marker, can be useful for diagnostic differentiation of MPE from NMPE, but weaker than PAP and better than D-dimer. TYPE OF STUDY AND LEVEL OF EVIDENCE: Level-II, Retrospective clinical cohort study.

Serum electrolyte concentrations and skeletal muscle excitability in vivo.

OBJECTIVE: Multi-fibre muscle velocity recovery cycle (MVRC) assessment is a well-tolerated method of evaluating sarcolemmal excitability in vivo that shows promise as a research tool and biomarker. MVRC parameters correlate with venous electrolyte concentrations in myopathies. We sought to determine the nature of any such relationships in individuals without muscle disease. METHODS: Tibialis anterior MVRCs were recorded and electrolyte concentrations measured from two groups of healthy volunteers. After studying a single measure cohort (n = 65, one recording/person), we studied a repeated measures cohort (n = 4, eight recordings/person) to better study intra-individual relationships using repeated measures correlation (rmcorr). RESULTS: In the single measure cohort, no significant correlations were present between MVRC parameters and electrolyte levels after accounting for age. In the repeated measures cohort, the relative refractory period (P < 0.01) and stimulus frequency measures (P < 0.01) correlated positively with potassium levels. Multiple late supernormality group measures correlated negatively with bicarbonate levels (P < 0.01). CONCLUSIONS: MVRC measures that vary with the resting muscle membrane potential correlate with venous potassium concentrations, as in myopathies. Late supernormality measures correlate with bicarbonate levels. SIGNIFICANCE: Determination of serum electrolyte levels may inform the interpretation of MVRC study results if variation in concentrations is anticipated to be significant.

Assessment of Patiromer Monotherapy for Hyperkalemia in an Acute Care Setting.

Importance: 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. Objective: To evaluate the outcomes associated with patiromer as monotherapy in patients with acute hyperkalemia in an acute care setting. Design, Setting, and Participants: 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. Exposures: A single dose of oral patiromer (8.4 g, 16.8 g, or 25.2 g). Main Outcomes and Measure: 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. Results: 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. Conclusions and Relevance: 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.

Decreased Iron Ion Concentrations in the Peripheral Blood Correlate with Coronary Atherosclerosis.

(1) Background: Obesity and diabetes continue to reach epidemic levels in the population with major health impacts that include a significantly increased risk of coronary atherosclerosis. The imbalance of trace elements in the body caused by nutritional factors can lead to the progression of coronary atherosclerosis. (2) Methods: We measured the concentrations of sodium (Na), potassium (K), magnesium (Mg), calcium (Ca), Zinc (Zn), and iron (Fe) in peripheral blood samples from 4243 patients and performed baseline analysis and propensity matching of the patient datasets. The patients were grouped into acute myocardial infarction (AMI, 702 patients) and stable coronary heart disease (SCAD1, 253 patients) groups. Both of these groups were included in the AS that had a total of 1955 patients. The control group consisted of 2288 patients. The plasma concentrations of calcium, magnesium, and iron were measured using a colorimetric method. For comparison, 15 external quality assessment (EQA) samples were selected from the Clinical Laboratory Center of the Ministry of Health of China. SPSS software was used for statistical analysis. The average values and deviations of all of the indicators in each group were calculated, and a p-value threshold of <0.05 was used to indicate statistical significance. (3) Results: The iron ion concentrations of the acute myocardial infarction (AMI) group were significantly lower than the control group (p < 0.05, AUC = 0.724, AUC = 0.702), irrespective of tendency matching. Compared to the data from the stable coronary artery disease (SCAD) group, the concentration of iron ions in the acute myocardial infarction group was significantly lower (p < 0.05, AUC = 0.710, AUC = 0.682). Furthermore, the iron ion concentrations in the (AMI + SCAD) group were significantly lower (p < 0.05) than in the control group. (4) Conclusions: The data presented in this study strongly indicate that the concentration of iron ions in the peripheral blood is related to coronary atherosclerosis. Decreases in the levels of iron ions in the peripheral blood can be used as a predictive biomarker of coronary atherosclerosis.

A mathematical model of the rat kidney. IV. Whole kidney response to hyperkalemia.

The renal response to acute hyperkalemia is mediated by increased K+ secretion within the connecting tubule (CNT), flux that is modulated by tubular effects (e.g., aldosterone) in conjunction with increased luminal flow. There is ample evidence that peritubular K+ blunts Na+ reabsorption in the proximal tubule, thick ascending Henle limb, and distal convoluted tubule (DCT). Although any such reduction may augment CNT delivery, the relative contribution of each is uncertain. The kidney model of this laboratory was recently advanced with representation of the cortical labyrinth and medullary ray. Model tubules capture the impact of hyperkalemia to blunt Na+ reabsorption within each upstream segment. However, this forces the question of the extent to which increased Na+ delivery is transmitted past the macula densa and its tubuloglomerular feedback (TGF) signal. Beyond increasing macula densa Na+ delivery, peritubular K+ is predicted to raise cytosolic Cl- and depolarize macula densa cells, which may also activate TGF. Thus, although the upstream reduction in Na+ transport may be larger, it appears that the DCT effect is critical to increasing CNT delivery. Beyond the flow effect, hyperkalemia reduces ammoniagenesis and reduced ammoniagenesis enhances K+ excretion. What this model provides is a possible mechanism. When cortical [Formula: see text] is taken up via peritubular Na+-K+([Formula: see text])-ATPase, it acidifies principal cells. Consequently, reduced ammoniagenesis increases principal cell pH, thereby increasing conductance of both the epithelial Na+ channel and renal outer medullary K+ channel, enhancing K+ excretion. In this model, the effect of aldosterone on principal cells, diminished DCT Na+ reabsorption, and reduced ammoniagenesis all provide relatively equal and additive contributions to renal K+ excretion.NEW & NOTEWORTHY Hyperkalemia blunts Na+ reabsorption along the nephron, and increased CNT Na+ delivery facilitates K+ secretion. The model suggests that tubuloglomerular feedback limits transmission of proximal effects past the macula densa, so that it is DCT transport that is critical. Hyperkalemia also reduces PCT ammoniagenesis, which enhances K+ excretion. The model suggests a mechanism, namely, that reduced cortical ammonia impacts CNT transport by raising cell pH and thus increasing both ENaC and ROMK conductance.