Pseudohypoaldosteronism type 2 (PHA2) is a rare inherited condition of altered tubular salt handling. It is characterized by the specific constellation of hyperkalaemic hyporeninemic hypertension, hyperchloremic metabolic acidosis and hypercalciuria. Molecular genetic testing confirms the diagnosis in the majority of cases. Thiazides constitute effective treatment. Due to its rarity, the diagnosis is often delayed. We here present two children with PHA2, who were initially treated with fludrocortisone and bicarbonate complicated mainly by exacerbation of their hypertension. Discontinuation of their previous therapy and commencement of thiazide diuretics led to normalisation of their blood pressure and electrolyte and acid-base status.

• Keywords
• Gordon syndrome, Hyporeninemic hypertension, Pseudohypoaldosteronism type 2, Thiazides,
• MeSH
• Acidosis * diagnosis   etiology   MeSH
• Child MeSH
• Fludrocortisone therapeutic use   MeSH
• Hyperkalemia * diagnosis   etiology   MeSH
• Hypertension * etiology   drug therapy   diagnosis   MeSH
• Blood Pressure * drug effects   MeSH
• Humans MeSH
• Pseudohypoaldosteronism * diagnosis   complications   drug therapy   genetics   physiopathology   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Names of Substances
• Fludrocortisone MeSH

BACKGROUND: Mineralocorticoid receptor antagonists (MRA) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF) but are underused in clinical practice. Observational data suggest that hyperkalemia is the leading obstacle for the suboptimal use of MRA. OBJECTIVES: This study sought to evaluate the effects of sodium zirconium cyclosilicate (SZC) in optimizing use of spironolactone among participants with HFrEF and hyperkalemia. METHODS: REALIZE-K (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients With Symptomatic HFrEF Receiving Spironolactone) was a prospective, double-blind, randomized- withdrawal trial in participants with HFrEF (NYHA functional class II-IV; left ventricular ejection fraction ≤40%), optimal guideline-directed therapy (except MRA), and prevalent or incident MRA-induced hyperkalemia. During open-label run-in, participants underwent spironolactone titration (target: 50 mg/day); those with hyperkalemia started SZC. Participants with normokalemia (potassium: 3.5-5.0 mEq/L) on SZC and spironolactone ≥25 mg/day were randomized to continued SZC or placebo for 6 months. The primary endpoint was optimal treatment response (normokalemia on spironolactone ≥25 mg/day without rescue therapy for hyperkalemia [months 1-6]). The 5 secondary endpoints were tested hierarchically. Exploratory endpoints included a composite of adjudicated cardiovascular death or worsening heart failure (HF) events (hospitalizations and urgent visits). RESULTS: Overall, 203 participants were randomized (SZC: 102; placebo: 101). Higher percentage of SZC- vs placebo-treated participants had optimal response (71% vs 36%; OR: 4.45; 95% CI: 2.89-6.86; P < 0.001). SZC (vs placebo) improved the first 4 secondary endpoints: normokalemia on randomization dose of spironolactone and without rescue therapy (58% vs 23%; OR: 4.58; 95% CI: 2.78-7.55; P < 0.001); receiving spironolactone ≥25 mg/day (81% vs 50%; OR: 4.33; 95% CI: 2.50-7.52; P < 0.001); time to hyperkalemia (HR: 0.51; 95% CI: 0.37-0.71; P < 0.001); and time to decrease/discontinuation of spironolactone due to hyperkalemia (HR: 0.37; 95% CI: 0.17-0.73; P = 0.006). There was no between-group difference in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score at 6 months (-1.01 points; 95% CI: -6.64 to 4.63; P = 0.72). Adverse events (64% vs 63%) and serious adverse events (23% vs 22%) were balanced between SZC and placebo, respectively. Composite of cardiovascular (CV) death or worsening HF occurred in 11 (11%) participants in the SZC group (1 with CV death, 10 with HF events) and 3 (3%) participants in the placebo group (1 with CV death, 2 with HF events; log-rank nominal P = 0.034). CONCLUSIONS: In participants with HFrEF and hyperkalemia, SZC led to large improvements in the percentage of participants with normokalemia while on optimal spironolactone dose, and reduced risk of hyperkalemia and down-titration/discontinuation of spironolactone. Although underpowered for clinical outcomes, more participants had HF events with SZC than placebo, which should be factored into the clinical decision making. (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients With Symptomatic HFrEF Receiving Spironolactone; NCT04676646).

• Keywords
• guideline-directed medical therapy, heart failure, hyperkalemia, mineralocorticoid receptor antagonists, sodium zirconium cyclosilicate,
• MeSH
• Mineralocorticoid Receptor Antagonists * adverse effects   therapeutic use   administration & dosage   MeSH
• Double-Blind Method MeSH
• Hyperkalemia * drug therapy   chemically induced   MeSH
• Middle Aged MeSH
• Humans MeSH
• Prospective Studies MeSH
• Aged MeSH
• Silicates * therapeutic use   administration & dosage   MeSH
• Spironolactone * adverse effects   therapeutic use   administration & dosage   MeSH
• Heart Failure * drug therapy   complications   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Mineralocorticoid Receptor Antagonists * MeSH
• Silicates * MeSH
• sodium zirconium cyclosilicate MeSH Browser
• Spironolactone * MeSH

BACKGROUND: Hyperkalaemia is a life-threatening electrolyte disturbance and also a potential cause of cardiac arrest. The objective was to assess the effects of acute pharmacological interventions for the treatment of hyperkalaemia in patients with and without cardiac arrest. METHODS: The review was reported according to PRISMA guidelines and registered on PROSPERO (CRD42023440553). We searched OVID Medline, EMBASE, and CENTRAL on September 9, 2024 for randomized trials, non-randomized trials, observational studies, and experimental animal studies. Two investigators performed abstract screening, full-text review, data extraction, and bias assessment. Outcomes included potassium levels, ECG findings, and clinical outcomes. Certainty of evidence was evaluated using GRADE. RESULTS: A total of 101 studies were included, with two studies including patients with cardiac arrest. In meta-analyses including adult patients without cardiac arrest, treated with insulin in combination with glucose, inhaled salbutamol, intravenous salbutamol dissolved in glucose, or a combination, the average reduction in potassium was between 0.7 and 1.2 mmol/l (very low to low certainty of evidence). The use of bicarbonate had no effect on potassium levels (very low certainty of evidence). In neonatal and paediatric populations, inhaled salbutamol and intravenous salbutamol reduced the average potassium between 0.9 and 1.0 mmol/l (very low to low certainty of evidence). There was no evidence to support a clinical beneficial effect of calcium for treatment of hyperkalemia. CONCLUSIONS: Evidence supports treatment with insulin in combination with glucose, inhaled or intravenous sal-butamol, or the combination. No evidence supporting a clinical effect of calcium or bicarbonate for hyperkalaemia was identified.

• Keywords
• Beta2-agonists, Bicarbonate, Calcium, Hyperkalaemia, Insulin, Pharmacological interventions, Systematic review,
• MeSH
• Albuterol administration & dosage   therapeutic use   MeSH
• Potassium blood   MeSH
• Hyperkalemia * drug therapy   complications   MeSH
• Insulin administration & dosage   therapeutic use   MeSH
• Humans MeSH
• Heart Arrest * etiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Systematic Review MeSH
• Names of Substances
• Albuterol MeSH
• Potassium MeSH
• Insulin MeSH

BACKGROUND: Hyperkalemia (HK) is associated with suboptimal renin-angiotensin system (RAS) inhibitor and mineralocorticoid receptor antagonist (MRA) use in heart failure with reduced ejection fraction (HFrEF). OBJECTIVES: This study sought to assess characteristics and RAS inhibitor/MRA use in patients receiving patiromer during the DIAMOND (Patiromer for the Management of Hyperkalemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure) run-in phase. METHODS: Patients with HFrEF and HK or past HK entered a run-in phase of ≤12 weeks with patiromer-facilitated RAS inhibitor/MRA optimization to achieve ≥50% recommended RAS inhibitor dose, 50 mg/d MRA, and normokalemia. Patients achieving these criteria (randomized group) were compared with the run-in failure group (patients not meeting the randomization criteria). RESULTS: Of 1,038 patients completing the run-in, 878 (84.6%) were randomized and 160 (15.4%) were run-in failures. Overall, 422 (40.7%) had HK entering run-in with a similar frequency in the randomized and run-in failure groups (40.3% vs 42.5%; P = 0.605). From start to the end of run-in, in the randomized group, an increase was observed in target RAS inhibitor and MRA use in patients with HK (RAS inhibitor: 76.8% to 98.6%; MRA: 35.9% to 98.6%) and past HK (RAS inhibitor: 60.5% to 98.1%; MRA: 15.6% to 98.7%). Despite not meeting the randomization criteria, an increase after run-in was observed in the run-in failure group in target RAS inhibitor (52.5% to 70.6%) and MRA use (15.0% to 48.1%). This increase was observed in patients with HK (RAS inhibitor: 51.5% to 64.7%; MRA: 19.1% to 39.7%) and past HK (RAS inhibitor: 53.3% to 75.0%; MRA: 12.0% to 54.3%). CONCLUSIONS: In patients with HFrEF and HK or past HK receiving suboptimal RAS inhibitor/MRA therapy, RAS inhibitor/MRA optimization increased during patiromer-facilitated run-in.

• Keywords
• heart failure, hyperkalemia, mineralocorticoid receptor antagonists, patiromer, renin–angiotensin system inhibitors,
• MeSH
• Mineralocorticoid Receptor Antagonists * therapeutic use   MeSH
• Angiotensin Receptor Antagonists therapeutic use   MeSH
• Hyperkalemia * drug therapy   blood   MeSH
• Angiotensin-Converting Enzyme Inhibitors therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Polymers * therapeutic use   MeSH
• Renin-Angiotensin System drug effects   MeSH
• Aged MeSH
• Heart Failure * drug therapy   MeSH
• Stroke Volume drug effects   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Mineralocorticoid Receptor Antagonists * MeSH
• Angiotensin Receptor Antagonists MeSH
• Angiotensin-Converting Enzyme Inhibitors MeSH
• patiromer MeSH Browser
• Polymers * MeSH

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF). However, MRAs are often underused because of hyperkalemia concerns. OBJECTIVES: The purpose of this study was to assess whether sodium zirconium cyclosilicate (SZC), a nonabsorbed crystal that traps and rapidly lowers potassium, enables MRA use in patients with HFrEF and prevalent hyperkalemia (or at high risk). METHODS: REALIZE-K is a prospective, double-blind, placebo-controlled trial in patients with HFrEF (NYHA functional class II-IV; left ventricular ejection fraction ≤40%), optimal therapy (except MRA), and prevalent hyperkalemia (or at high risk). During the open-label run-in, all participants underwent protocol-mandated spironolactone titration (target: 50 mg daily); those with prevalent (cohort 1) or incident (cohort 2) hyperkalemia during titration started SZC. Participants achieving normokalemia while on spironolactone ≥25 mg daily were randomized to continuing SZC or matching placebo for 6 months. The primary composite endpoint was proportion of participants with optimal response (normokalemia, on spironolactone ≥25 mg daily, no rescue for hyperkalemia [months 1-6]). RESULTS: Of 365 patients (run-in), 202 were randomized. Baseline characteristics included mean age 70 years, prevalent comorbidities (78% estimated glomerular filtration rate <60 mL/min/1.73 m2, 38% atrial fibrillation/flutter), high N-terminal pro B-type natriuretic peptide (median 1,136 pg/mL), and high HFrEF therapy use (64% sacubitril/valsartan, 96% beta-blocker, 42% sodium glucose co-transporter 2 inhibitor). At randomization, 78% were receiving spironolactone 50 mg daily. CONCLUSIONS: REALIZE-K is the first trial to evaluate whether SZC can enable rapid and safe MRA optimization and long-term continuation in patients with HFrEF and prevalent/high risk of hyperkalemia. (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients with Symptomatic HFrEF Receiving Spironolactone [REALIZE-K]; NCT04676646).

• Keywords
• guideline-directed medical therapy, heart failure, hyperkalemia, mineralocorticoid receptor antagonists, sodium zirconium silicate,
• MeSH
• Mineralocorticoid Receptor Antagonists * therapeutic use   administration & dosage   adverse effects   MeSH
• Double-Blind Method MeSH
• Hyperkalemia * drug therapy   MeSH
• Middle Aged MeSH
• Humans MeSH
• Prospective Studies MeSH
• Aged MeSH
• Silicates * therapeutic use   administration & dosage   MeSH
• Spironolactone * administration & dosage   therapeutic use   adverse effects   MeSH
• Heart Failure * drug therapy   physiopathology   MeSH
• Stroke Volume * physiology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Mineralocorticoid Receptor Antagonists * MeSH
• Silicates * MeSH
• sodium zirconium cyclosilicate MeSH Browser
• Spironolactone * MeSH

This article provides a comprehensive overview of electrolyte and water homeostasis in pediatric patients, focusing on some of the common serum electrolyte abnormalities encountered in clinical practice. Understanding pathophysiology, taking a detailed history, performing comprehensive physical examinations, and ordering basic laboratory investigations are essential for the timely proper management of these conditions. We will discuss the pathophysiology, clinical manifestations, diagnostic approaches, and treatment strategies for each electrolyte disorder. This article aims to enhance the clinical approach to pediatric patients with electrolyte imbalance-related emergencies, ultimately improving patient outcomes.Trial registration This manuscript does not include a clinical trial; instead, it provides an updated review of literature.

• Keywords
• Electrolyte imbalances, Hypercalcemia, Hyperkalemia, Hypernatremia, Hypocalcemia, Hypokalemia, Hyponatremia, Pediatrics,
• MeSH
• Acidosis diagnosis   blood   therapy   MeSH
• Child MeSH
• Electrolytes blood   MeSH
• Hypercalcemia therapy   blood   diagnosis   etiology   MeSH
• Hyperkalemia therapy   diagnosis   blood   etiology   MeSH
• Hypernatremia therapy   diagnosis   etiology   physiopathology   MeSH
• Hypocalcemia diagnosis   etiology   therapy   MeSH
• Hypokalemia therapy   diagnosis   blood   etiology   MeSH
• Hyponatremia therapy   etiology   diagnosis   MeSH
• Humans MeSH
• Emergencies * MeSH
• Acid-Base Imbalance diagnosis   therapy   physiopathology   MeSH
• Water-Electrolyte Imbalance * therapy   MeSH
• Water-Electrolyte Balance physiology   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Electrolytes MeSH

Valproate is known to disturb the kidney function, and high doses or prolonged intake may cause serum ion imbalance, kidney tubular acidosis, proteinuria, hyperuricosuria, polyuria, polydipsia, and dehydration. The aim of this in vivo study was to see whether naringin would counter the adverse effects of high-dose valproate in C57Bl/6 mice and to which extent. As expected, valproate (150 mg/kg bw a day for 10 days) caused serum hyperkalaemia, more in male than female mice. Naringin reversed (25 mg/kg bw a day for 10 days) the hyperkalaemia and activated antioxidative defence mechanisms (mainly catalase and glutathione), again more efficiently in females. In males naringin combined with valproate was not as effective and even showed some prooxidative effects.

Valproat je jedan od najčešće primjenjivanih antiepileptika, a poznato je da prouzročuje poremećenu funkciju proksimalnih bubrežnih tubula. Fiziološki poremećaji i nefrotoksični učinci u nekih bolesnika nakon visokih doza ili produljenog uzimanja valproata uključuju disbalans iona u serumu, bubrežnu tubularnu acidozu, proteinuriju, hiperurikozuriju, poliuriju, polidipsiju, dehidraciju i druge poremećaje. U okviru ovog eksperimentalnog rada primijenili smo visoke doze valproata i združeni tretman valproata i naringina u C57Bl/6 miševa. Naringin je poznati antioksidans i protuupalna flavonoidna molekula iz citrusnog voća. Cilj rada bio je utvrditi mogu li biološka svojstva naringina umanjiti štetne učinke na bubrege nakon tretmana valproatom. Valproat je in vivo prouzročio serumsku hiperkalijemiju, izraženiju u mužjaka nego u ženki miševa. Hiperkalijemija prouzročena valproatom bila je ublažena naringinom, a antioksidacijski obrambeni mehanizmi (uglavnom katalaza i smanjena glutationacija) bili su aktivirani, više u ženki. U mužjaka, zajednički tretman valproatom i naringinom nije bio tako učinkovit, a rezultati upućuju na moguće prooksidacijsko djelovanje u bubrežnom tkivu kada se obje tvari primjenjuju zajedno.

• Keywords
• calcium, catalase, hiperkalijemija, hyperkalaemia, kalcij, kalij, katalaza, malondialdehid, malondialdehyde, oksidacijski stres, oxidative stress, potassium, sodium, superoksid dismutaza, superoxide dismutase,
• MeSH
• Antioxidants * pharmacology   MeSH
• Hyperkalemia * MeSH
• Catalase metabolism   pharmacology   MeSH
• Valproic Acid toxicity   MeSH
• Kidney MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Oxidative Stress MeSH
• Lipid Peroxidation MeSH
• Superoxide Dismutase metabolism   pharmacology   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antioxidants * MeSH
• Catalase MeSH
• Valproic Acid MeSH
• naringin MeSH Browser
• Superoxide Dismutase MeSH

AIMS: To investigate the impact of patiromer on the serum potassium level and its ability to enable specified target doses of renin-angiotensin-aldosterone system inhibitor (RAASi) use in patients with heart failure and reduced ejection fraction (HFrEF). METHODS AND RESULTS: A total of 1642 patients with HFrEF and current or a history of RAASi-related hyperkalemia were screened and 1195 were enrolled in the run-in phase with patiromer and optimization of the RAASi therapy [≥50% recommended dose of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, and 50 mg of mineralocorticoid receptor antagonist (MRA) spironolactone or eplerenone]. Specified target doses of the RAASi therapy were achieved in 878 (84.6%) patients; 439 were randomized to patiromer and 439 to placebo. All patients, physicians, and outcome assessors were blinded to treatment assignment. The primary endpoint was between-group difference in the adjusted mean change in serum potassium. Five hierarchical secondary endpoints were assessed. At the end of treatment, the median (interquartile range) duration of follow-up was 27 (13-43) weeks, the adjusted mean change in potassium was +0.03 mmol/l in the patiromer group and +0.13 mmol/l in the placebo group [difference in the adjusted mean change between patiromer and placebo: -0.10 mmol/l (95% confidence interval, CI -0.13, 0.07); P < 0.001]. Risk of hyperkalemia >5.5 mmol/l [hazard ratio (HR) 0.63; 95% CI 0.45, 0.87; P = 0.006), reduction of MRA dose (HR 0.62; 95% CI 0.45, 0.87; P = 0.006), and total adjusted hyperkalemia events/100 person-years (77.7 vs. 118.2; HR 0.66; 95% CI 0.53, 0.81; P < 0.001) were lower with patiromer. Hyperkalemia-related morbidity-adjusted events (win ratio 1.53, P < 0.001) and total RAASi use score (win ratio 1.25, P = 0.048) favored the patiromer arm. Adverse events were similar between groups. CONCLUSION: Concurrent use of patiromer and high-dose MRAs reduces the risk of recurrent hyperkalemia (ClinicalTrials.gov: NCT03888066).

• Keywords
• Heart failure with reduced ejection fraction, Hyperkalemia, Patiromer, Potassium-binding polymer, Renin–angiotensin–aldosterone system inhibitor (RAASi),
• MeSH
• Mineralocorticoid Receptor Antagonists adverse effects   MeSH
• Potassium MeSH
• Hyperkalemia * drug therapy   complications   MeSH
• Humans MeSH
• Renin-Angiotensin System MeSH
• Heart Failure * complications   drug therapy   MeSH
• Stroke Volume MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Mineralocorticoid Receptor Antagonists MeSH
• Potassium MeSH
• patiromer MeSH Browser

• MeSH
• Potassium MeSH
• Hyperkalemia * epidemiology   therapy   MeSH
• Humans MeSH
• Emergency Service, Hospital MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Letter MeSH
• Comment MeSH
• Names of Substances
• Potassium MeSH

To enable diagnosis of hyperkalemia from the perimortem blood sample, we aim to describe the natural dynamics of blood potassium [K+ ] in patients dying after withdrawal of care while in an intensive care unit. In a nested sub-study of international Death Prediction and Physiology after Removal of Therapy (DePPaRT) project, we obtained serial whole-blood samples and analyzed ions and acid-base parameters in 23 patients just before life-sustaining treatment withdrawal, at the time of death, and after 5 and 30 min after death. Of the 631 patients in the DePPaRT study, we obtained consent and enrolled 23 subjects in the [K+ ] sub-study (12 M, 11F, aged 73 ± 14 years), mostly dying from irreversible brain damage or multi-organ failure. Blood [K+ ] rose from the median 4.3 (IQR 3.9; 4.8) mEq/L at treatment withdrawal to 5.2 (IQR 5.0; 6.8) mEq/L at death and then to 5.85 (IQR 5.2; 6.8) mEq/L after 30 min (mean rise of +0.64 mEq.L-1 .h-1 ). These changes were associated with progressive lactic and hypercapnic acidemia. After correcting the measured [K+] for pH by subtracting 0.6 mEq/L from [K+] for every 0.1 pH decrease from 7.40, the calculated [K+] remained normal or decreased from that measured at treatment withdrawal. In contrast to the late autolysis phase, the early changes of blood [K+ ] after death are slow and can be fully explained by progressive acidemia. Our data suggest that the diagnosis of hyperkalemia at death from a blood sample obtained within 30 min after death can be made by adjusting the [K+] concentration to a pH 7.40.

• Keywords
• dynamics of blood potassium, forensic pathology, hyperkalemia, perimortem blood potassium, perimortem changes, physiology of dying, postmortem chemistry,
• MeSH
• Potassium * MeSH
• Hyperkalemia * complications   MeSH
• Ions MeSH
• Intensive Care Units MeSH
• Cohort Studies MeSH
• Humans MeSH
• Prospective Studies MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Potassium * MeSH
• Ions MeSH