Severe Hyperkalemia Research Articles

Severe Hyperkalemia in a Child with Vomiting and Diarrhea

Case Presentation: A 13-month-old child with past medical history of congenital adrenal insufficiency presented to the emergency department with vomiting and diarrhea. Initially the child was noticed to have bradycardia with normal blood pressure. An electrocardiogram (ECG) showed tall T waves, broad QRS complex, and widened PR interval suggestive of severe hyperkalemia. The initial blood gas showed potassium of 10.7 millimoles per liter. The patient was started on calcium gluconate with immediate resolution of ECG changes. Further management with insulin, dextrose, and sodium olystyrene sulfonate led to normal potassium levels. Discussion: Hyperkalemia is a life-threatening condition in children, especially in those with congenital adrenal insufficiency. The ECG showed different changes as the levels of serum potassium levels increased ranging from tall T waves, wide QRS complex, increased PR interval to arrythmias. Immediate treatment with calcium gluconate in such cases has significant cardioprotective effect. It is important to recognize the ECG changes manifested by changes in serum potassium levels. Our patient had classic ECG changes manifested in severe hyperkalemia.

A Delphi consensus project to capture experts' opinion on hyperkalaemia management across the cardiorenal spectrum.

The main purpose of this project was to capture experts' opinion on hyperkalaemia management and form best practice recommendations for cardiorenal patients in Greece. A steering committee of nephrologists and cardiologists developed 37 statements. An online questionnaire completed by 32 experts in cardiorenal management in Greece. Median score used to determine the level of agreement and disagreement index (DI) used to determine the level of consensus for each statement. Statements divided in four sectors: hyperkalaemia risk management, preventative measures, treatment and collaboration between specialties. The rate of the first round of the consensus was 94.6%. Median score was >7 for 36 of 37 statements and DI≤1 for 35 of 37. Among other statements, consensus reached for recognizing levels K+>5.0mEq/L as associated with elevated mortality risk; retaining renin-angiotensin-aldosterone system inhibitors (RAASi) on maximum recommended dose for cardiorenal patients; and using novel K+ binders to help enabling guideline-recommended doses of RAASi therapy. Cardiologists compared to nephrologists showed higher reluctance to discontinue down-titrate RAASi and MRA in patients with K+ levels above 5mEq/L. Additionally, 88.9% of nephrologists and 71.4% of cardiologists agreed that cross-specialty alignment on a serum K+ concentration level (K>5.5mEq/L) is needed to initiate hyperkalaemia treatment. Both cardiologists and nephrologists showed disagreement with the statement on keeping titration in cardiorenal patients with K+>5.5mEq/L or preserving fruit and vegetable consumption when moderate or severe hyperkalaemia exhibits. This Delphi project pointed out nephrologists' and cardiologists' agreement on hyperkalaemia management in cardiorenal patients; thus, it can help a cross-specialty optimal management of cardiorenal patients, with hyperkalaemia not being an obstacle for disease-optimizing therapy. Novel potassium binding agents can enable guideline-recommended doses of potassium-sparing medication.

Understanding the benefits of renin-angiotensin-aldosterone system inhibitors and influence of hyperkalaemia on their prescription: a UK survey of healthcare professionals' views and practice

Abstract Background Renin–angiotensin–aldosterone system inhibitors (RAASi) improve outcomes in heart failure with reduced ejection fraction (HFrEF) and they should be increased to the maximally tolerated dose. However, their use is often hindered by hyperkalaemia leading to discontinuation or down titration. Purpose Assess perceptions of primary and secondary healthcare professionals regarding benefits of RAASi according to indication and, in the context of developing hyperkalaemia, to identify barriers to optimal utilisation, and to explore options for improving management protocols, specifically in HFrEF. Methods An electronic survey was distributed in primary and secondary care setting in Hampshire, UK, to evaluate knowledge about benefits of RAASi, clinical response to varying level of potassium (K+), and decision-making using several clinical scenarios. Hyperkalaemia was graded into mild (serum K+ 5.5 – 5.9 mmol/L), moderate (serum K+ 6.0 – 6.4 mmol/L) or severe (serum K+ ≥ 6.5 mmol/L). Results Between November 2021 and January 2023, 300 questionnaires were completed by 274 (91%) physicians (varying grades of seniority), 22 (7%) non-medical prescribers, and 4 (1%) pharmacists. 80% were working in secondary care across different specialities (31 working in cardiology and 15 in nephrology). The majority were aware of prognostic benefit of angiotensin converting enzyme inhibitors (ACEi) in patients with HFrEF although this was lower for mineralocorticoid receptor antagonists (MRA) (Fig 1). Fewer than 2/3 of respondents were aware of impact of ACEi on symptoms. In the presence of mild hyperkalaemia, 75% and 88% of healthcare professionals would stop or reduce ACEi and MRA, respectively. In moderate or severe hyperkalaemia, this increased to 96% and 97%, respectively (Fig 2A-B). When considering the scenario of a patient with HFrEF who had ACEi stopped due to K+ 5.9 mmol/L, the potassium at which the responder would consider re-starting the ACEi ranged from 77% when potassium level < 5.5 mmol/L to 1% in moderate or severe hyperkalaemia (Fig 2C). 74% of healthcare professionals were familiar with local hyperkalaemia management protocol and 93% supported dedicated training on RAASi dose adjustment and hyperkalaemia management. Conclusion This survey, across a broad range of healthcare professionals, shows uncertainties around knowledge of benefits of RAASi in patients with HFrEF and there is sizeable variation in the prescribing response to degrees of hyperkalaemia. Given the voluntary nature of the survey, it is plausible that these data are biased towards individuals with greater understanding. Regardless, there is a need for continued education with a goal of improving patient-centred care.

The safety of in-hospital initiation of SGLT2 inhibitor with MRA therapy in patients hospitalized for heart failure with a reduced left ventricular ejection fraction and chronic kidney disease

Abstract Deferring in-hospital initiation of guideline-recommended medications in HFrEF has a few chances they will be initiated ambulatory, especially in the case of coexisting HFrEF and chronic kidney disease (CKD). The aim was to investigate the safety of in-hospital initiation of SGLT2i with MRA therapy for patients hospitalized for HFrEF and CKD 3. Methods 88 patients with HFrEF (on top of standard therapy ACE-I/ARB, B-blockers) and CKD (baseline eGFR between 30 and 60 ml/min) were included in the study. The potassium (K), creatinine (C), uric acid (UA) levels were estimated at baseline and week 12. After biochemical evaluation, patients started on spironolactone (SP) treatment with a median dose of 20 mg daily (titrated) and dapagliflozin (D) with a dose of 10 mg daily (D+SP). Blood pressure (BP), K, and renal function (RF) were checked at weeks 1 (in-hospital), 2, 4, 6, 8, 12 (ambulatory), and more frequently as necessary. Results After the start of therapy D+SP mean eGFR decreased significantly at week 1 from 51.14±9.18 to 46.26±7.91 ml/min/1.73m2 (P<.0001) and at week 2 to 44.18±6.51 ml/min/1.73m2 (-2.08±1.2; P<.001). At week 4 mean eGFR decreased to 42.73±6.86 ml/min/1.73m2 (-1.45±1.1; P<.05). So, a significant decrease in eGFR was observed only during the first month with no significant decrease at 6 and 12 weeks after the start of therapy. Six patients (8%) experienced a significant decline in RF resulting in temporary withdrawal of SP. At week 2 mean K level increased significantly from 4.56±0.63 to 5.07±0.57 mmol/L (P<.001). At weeks 4, 6, 8 K levels remain stable. At week 12 mean K level decreased significantly compared with week 2 (to 4.92±0.57 mmol/L, P<.05). The incidences of severe hyperkalemia (HK) (K+≥6.0mmol/L) were in three patients < 2 %, and moderate HK (K 5.5–5.9 mmol/L) occurred in ten patients (11 %). Patients who experienced inpatient hyperkalemia had a significantly lower eGFR than patients without episodes of HK (38.70 vs. 55.21 mL/min/1.73 m2; P<.0001). Episodes of HK were predicted by baseline K≥5.0 mmol/L and eGFR≤40 ml/min/1.73m2. Additionally, there was a significant improvement in blood UA (-1,53±0.49 mg/dL, P<.01). By multivariate analysis older age, diabetes, low diastolic BP (<60 mm Hg), eGFR≤40 ml/min/1.73m2 at baseline were associated with decreased RF (0.378, P<.01; 0.632, P<.001; 0.771, P<.0001; 0.397, P<.01; respectively), whereas episodes of HK were predicted by baseline K≥5.0 mmol/L and eGFR≤40 ml/min/1.73m2 (0.785, P<.0001; 0.542, P<.001; respectively). Conclusion Initiation of SGLT2i with MRA in patients hospitalized for HFrEF and CKD 3 was mainly safe although it caused an early drop in eGFR. Importantly, a fall in eGFR was observed during the first month. Concern about the reduction in eGFR should be in older diabetic patients with eGFR≤40 and low diastolic blood pressure. Although hyperkalemia was common, the occurrence of it was predicted by baseline potassium level and eGFR.

The Harm of Inappropriate Central Line Blood Cultures in Clinical Practice

This case report describes a 57-year-old man with end-stage kidney disease who was receiving hemodialysis through a tunneled central venous catheter and had severe hyperkalemia that prompted admission for emergent hemodialysis.

Evaluation of Monotherapy Sodium Zirconium Cyclosilicate Versus Sodium Polystyrene Sulfonate for Acute Hyperkalemia: A Cohort Study.

Comparison of monotherapy sodium zirconium cyclosilicate (SZC) versus sodium polystyrene sulfonate (SPS) is lacking. We aimed to evaluate the effectiveness of SZC versus SPS for acute potassium lowering. This retrospective cohort study included hospitalized adult patients with acute hyperkalemia treated with SZC or SPS monotherapy. The primary outcome was time to normalization of serum potassium. Secondary outcomes included necessity of additional treatment, achievement of normokalemia at 1, 2, 4, 8, and 24 hours, and change in serum potassium from baseline to 1, 2, 4, 8, and 24 hours. Fifty-one patients received SZC and 50 received SPS. Mean baseline potassium was 5.4 mmol/L for both groups. Median time to normokalemia was 14 (IQR 8-20) hours in the SZC group versus 17 (IQR 10-21) hours in the SPS group (P = .26). Normokalemia was achieved at 24 hours in 80% versus 77% in each group, respectively (P = .56). Six patients per group required additional treatment (P = .97). Mean serum potassium at all time points was numerically lower with SZC, but statistical significance was only observed at hour 8 (4.6 vs 5.0 mmol/L, P = .005), which was associated with a -0.77 versus -0.51 mmol/L decrease in serum potassium from baseline in each group, respectively (P = .026). SZC monotherapy is at least as effective as SPS in treating mild hyperkalemia and may reduce serum potassium more quickly and to a greater degree than SPS. Future research in more severe hyperkalemia and with monitoring of potassium at regular intervals is needed to better understand the role and potential advantages of SZC over SPS.

Hyperkalemia and maintenance of renin-angiotensin system inhibitor therapy after initiating SGLT-2 or DPP-4 inhibitors.

Post-hoc analyses of clinical trials suggest that sodium-glucose cotransporter-2 inhibitors (SGLT-2i) lower the risk of hyperkalemia and facilitate the use of renin-angiotensin system inhibitors (RASi) in people with type 2 diabetes. Whether this is also observed in routine care is unclear. We investigated whether SGLT-2i lowered the risk of hyperkalemia and RASi discontinuation as compared to dipeptidyl peptidase 4 inhibitors (DPP-4i). Using the target trial emulation framework, we studied adults with type 2 diabetes (T2D) who started SGLT-2i or DPP-4i in Stockholm, Sweden (2014-2021). The outcomes were incident hyperkalaemia (potassium>5.0 mmol/L), mild hyperkalemia (potassium>5-≤5.5mmol/L) and moderate to severe hyperkalemia (potassium>5.5mmol/L). Among RASi users, we studied time to RASi discontinuation through evaluation of pharmacy fills. Cox regression with inverse probability of treatment weighting was used to estimate per-protocol hazard ratios (HRs). 29 849 individuals (15 326 SGLT-2i and 14 523 DPP-4i initiators) were included (mean age 66 years, 37% women). About one third of participants in each arm discontinued treatment within a year. Compared with DPP-4i, SGLT-2i use was associated with a lower rate of hyperkalemia (HR 0.77; 95% CI: 0.64-0.93), including both mild (0.76; 0.62-0.93) and moderate/severe (0.53; 0.40-0.69) hyperkalemia events. Of 19.116 participants that used RASi at baseline, 7% discontinued therapy. Initiation of SGLT-2i vs. DPP-4i was not associated with the rate of RASi discontinuation (0.97; 0.83-1.14). Results were consistent in intention-to-treat analyses and across strata of age, sex, cardiovascular comorbidity, and baseline kidney function. In patients with diabetes managed in routine clinical care, the use of SGLT-2i was associated with lower rates of hyperkalemia compared with DPP-4i. Possibly because of a relatively high rate of treatment discontinuations, this was not accompanied by higher persistence on RASi therapy.

Sudden cardiac death due to adrenal insufficiency masquerading as Brugada syndrome. Case report

Sudden cardiac death in young people in 20% of cases is caused by cardiomyopathies and channelopathies. One of the forms of channelopathies is Brugada syndrome, a hereditary disease characterized by ST segment elevation in the right precordial leads (V1-V3) and an increased risk of sudden cardiac death in the absence of structural heart disease. Brugada phenocopies are also known – clinical situations that are manifested by electrocardiogram (ECG) patterns identical to true Brugada syndrome. They are caused by different clinical circumstances and form a group of heterogeneous conditions that are often difficult to distinguish from true congenital Brugada syndrome due to identical ECG patterns. The formation of Brugada phenocopy due to hyperkalemia is presented in the literature in various conditions: with renal failure, after extensive trauma, application of medications. The article presents a case report demonstrating a rare cause of sudden cardiac arrest in a young patient without a history of cardiovascular pathology: the occurrence of the Brugada pattern on the ECG due to severe hyperkalemia in adrenal insufficiency. The stages of the differential diagnostic search are described, which made it possible to verify the final diagnosis and prescribe effective hormone replacement therapy. Performing a provocative test with novocanamide allowed us to confirm that the patient had a phenocopy, and not Brugada syndrome. Differential diagnosis of phenocopies of Brugada syndrome – a series of often life-threatening cardiac and non-cardiac diseases and conditions, manifested by similar ECG changes in the form of a peculiar ST segment elevation in leads V1-V3, is often a difficult task. This case represents a phenocopy of Brugada in the setting of severe hyperkalemia with development of cardiac arrest due to adrenal insufficiency, which resolved with correction of electrolyte abnormalities and treatment of the underlying disease. Typical ECGs are presented: a graph of the Brugada phenomenon, hyperkalemia, a sinusoidal curve during cardiac arrest, recorded over time in a patient, and the pathogenetic mechanisms causing the formation of the Brugada pattern in adrenal insufficiency are explained.

A Retrospective Analysis of Patients Presenting with Acute Hyperkalemia in an Emergency Care Setting.

We aimed to analyze the clinical characteristics and prognostic factors of patients with severe hyperkalemia in the emergency department. This retrospective cohort study included adult patients diagnosed with severe hyperkalemia who sought medical care at the emergency department of Aerospace Center Hospital between January 2018 and May 2022. Clinical data, including demographics, comorbidities, laboratory findings, and outcomes, were systematically collected. Patients were categorized into survival and deceased groups based on in-hospital mortality. Comparative analysis between these groups identified significant differences, highlighting key clinically covariates. Binary logistic regression was employed to determine the primary factors influencing patient outcomes. Of 90 patients diagnosed with severe hyperkalemia, 64 were in the survival group, and 26 in the deceased group. Binary logistic regression identified several significant predictors of mortality, including higher APACHE II scores (odds ratio [OR] 1.41, P = 0.02), widened QRS wave on electrocardiogram (ECG) (OR 79.39, P = 0.04), and elevated serum potassium levels (OR 1.3, P = 0.04). In contrast, emergency blood purification was associated with a reduced mortality rate (OR 0.29, P = 0.03). Key risk factors for mortality in patients with severe hyperkalemia include widened QRS wave on ECG, elevated APACHE II score, and high serum potassium level. Timely correction of hyperkalemia through emergency blood purification significantly improves patient outcomes.

Serum Potassium Monitoring UsingAI-Enabled Smartwatch Electrocardiograms.

Hyperkalemia, characterized by elevated serum potassium levels, heightens the risk of sudden cardiac death, particularly increasing risk for individuals with chronic kidney disease and end-stage renal disease (ESRD). Traditional laboratory test monitoring is resource-heavy, invasive, and unable to provide continuous tracking. Wearable technologies like smartwatches with electrocardiogram (ECG) capabilities are emerging as valuable tools for remote monitoring, potentially allowing for personalized monitoring with artificial intelligence (AI)-ECG interpretation. The purpose of this study was to develop an AI-ECG algorithm to predict serum potassium level in ESRD patients with smartwatch-generated ECG waveforms. A cohort of 152,508 patients with 293,557 ECGs paired serum potassium levels obtained within 1 hour at Cedars Sinai Medical Center was used to train an AI-ECG model ("Kardio-Net") to predict serum potassium level. The model was further fine-tuned on 4,337 ECGs from 1,463 patients with ESRD using inputs from 12- and single-lead ECGs. Kardio-Net was evaluated in held-out test cohorts from Cedars Sinai Medical Center and Stanford Healthcare (SHC) as well as a prospective international cohort of 40 ESRD patients with smartwatch ECGs at Chang Gung Memorial Hospital. The Kardio-Net, when applied to 12-lead ECGs, identified severe hyperkalemia (>6.5 mEq/L) with an AUC of 0.852 (95%CI: 0.745-0.956) and a mean absolute error (MAE) of 0.527 mEq/L. In external validation at SHC, the model achieved an AUC of 0.849 (95%CI: 0.823-0.875) and an MAE of 0.599 mEq/L. For single-lead ECGs, Kardio-Net detected severe hyperkalemia with an AUC of 0.876 (95%CI: 0.765-0.987) in the primary cohort and had an MAE of 0.575 mEq/L. In the external SHC validation, the AUC was 0.807 (95%CI: 0.778-0.835) with an MAE of 0.740 mEq/L. Using prospectively obtained smartwatch data, the AUC was 0.831 (95%CI: 0.693-0.975), with an MAE of 0.580 mEq/L. We validate a deep learning model to predict serum potassium levels from both 12-lead ECGs and single-lead smartwatch data, demonstrating its utility for remote monitoring of hyperkalemia.

Efficacy and safety analysis of sodium zirconium cyclosilicate and calcium polystyrene sulfonate on rapid reduction of potassium in moderate to severe hyperkalemia patients with chronic kidney disease without dialysis.

Hyperkalemia is a common complication of chronic kidney disease (CKD). This study aims to investigate the efficacy and safety of sodium zirconium cyclosilicate and calcium polystyrene sulfonate in reducing potassium in patients with acute and severe hyperkalemia in CKD who are not undergoing dialysis. A retrospective real-world study was conducted among 73 patients with non-dialysis chronic kidney disease who were hospitalized in the First Affiliated Hospital of Chengdu Medical College from June 2020 to June 2022. 33 patients treated with sodium zirconium cyclosilicate were categorized as SZC group, and the other 40 patients treated with calcium polystyrene sulfonate were categorized as CPS group. Serum potassium, serum sodium, magnesium, calcium, and phosphorus levels were examined. Adverse reactions were recorded during medication. Significantly decreased serum potassium was observed in both groups, whereas the potassium reduction was higher in the SZC group than in the CPS group at 2, 4, 24, and 48 hours after medication while there was no statistically significant difference in the serum potassium level between the two groups at 72 hours. For those people whose initial potassium exceeded 6 mmol/L, the potassium reduction was more obvious in the SZC group than in the CPS group at 2 and 4 hours after medication. The control rate of hyperkalemia in the SZC group was significantly higher than in the CPS group at 4, 24, and 48 hours. No distinct change was observed in serum sodium, calcium, magnesium, and phosphorus before and 72 hours after medication. No severe adverse reactions occurred. Sodium zirconium cyclosilicate has a more obvious effect on reducing potassium particularly for those patients with moderate to severe hyperkalemia who need rapid potassium reduction.

BRAНH syndrome: clinical case

The article describes a clinical case of BRAHH syndrome in a patient with arterial hypertension and permanent atrial fibrillation (AF). The patient took perindopril 10 mg, indapamide 2.5 mg, amlodipine 10 mg, bisoprolol 2.5-5 mg daily. She was admitted to a hospital complaining of severe weakness, a heart rate decreases to 38 beats per minute against the background of high blood pressure. During the examination, she was diagnosed with complete atrioventricular block against the background of AF, stage 4 chronic kidney disease and severe hyperkalemia (potassium 8.7 mmol/l). The patient was prescribed treatment aimed at eliminating hyperkalemia, and temporary pacing was established. Against this background, her condition improved, and the complete atrioventricular blockade was resolved. This clinical example meets the criteria of BRAHH syndrome, since against the background of taking an atrioventricular node blocker in a small dose, a patient with chronic kidney disease and severe hyperkalemia developed complete atrioventricular block against the background of AF, accompanied by high blood pressure.

Efficacy and safety of angiotensin receptor-neprilysin inhibition in heart failure patients with end-stage kidney disease on maintenance dialysis: A systematic review and meta-analysis.

Angiotensin receptor-neprilysin inhibitor (ARNI) has played an increasingly important role in the management of heart failure (HF). However, the evidence on the benefits of ARNI in HF patients with end-stage kidney disease (ESKD) undergoing dialysis is limited. This study aimed to investigate the efficacy and safety of ARNI in patients with concomitant HF and ESKD on maintenance dialysis. We systematically searched the MEDLINE, Embase, Web of Science, Cochrane, and ClinicalTrials.gov databases for studies reporting outcomes after ARNI treatment in HF patients with ESKD on dialysis. All meta-analyses were performed using the random effects model. Twenty-six studies comprising 2494 patients with concomitant HF and ESKD undergoing dialysis were included. Our synthesis showed a significant improvement in left ventricular ejection fraction (LVEF) between before and after ARNI treatment (mean change: 8.05%; 95% confidence interval [CI] 5.57-10.54). Compared to the conventional group, the ARNI group showed a greater improvement in LVEF (mean difference: 4.03%; 95% CI 2.90-5.16). This effect was more pronounced in patients with HF with reduced ejection fraction (pinteraction < 0.0001). Patients treated with ARNI had a lower risk of all-cause mortality (risk ratio [RR] 0.64; 95% CI 0.45-0.92; p = 0.01) but had a similar rate of HF hospitalization (RR 0.71; 95% CI 0.43-1.18; p = 0.19). ARNI treatment showed benefits in the improvement of left ventricular end-systolic diameter, left ventricular mass index, left atrial diameter, and E/e' ratio (p < 0.05), while it did not significantly increase the risk of severe hyperkalaemia (p = 0.33) or symptomatic hypotension (p = 0.53). This meta-analysis provided insights into the benefits of ARNI in HF patients with ESKD undergoing dialysis by improving left ventricular function, reversing left ventricular remodelling, and reducing the risk of all-cause mortality, without increasing the risk of HF hospitalizations, severe hyperkalaemia, and symptomatic hypotension.

GLP-1RA vs DPP-4i Use and Rates of Hyperkalemia and RAS Blockade Discontinuation in Type 2 Diabetes

Hyperkalemia is a common complication in people with type 2 diabetes (T2D) that may limit the use of guideline-recommended renin-angiotensin system inhibitors (RASis). Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase urinary potassium excretion, which may translate into reduced hyperkalemia risk. To compare rates of hyperkalemia and RASi persistence among new users of GLP-1RAs vs dipeptidyl peptidase-4 inhibitors (DPP-4is). This cohort study included all adults with T2D in the region of Stockholm, Sweden, who initiated GLP-1RA or DPP-4i treatment between January 1, 2008, and December 31, 2021. Analyses were conducted between October 1, 2023, and April 29, 2024. GLP-1RAs or DPP-4is. The primary study outcome was time to any hyperkalemia (potassium level >5.0 mEq/L) and moderate to severe (potassium level >5.5 mEq/L) hyperkalemia. Time to discontinuation of RASi use among individuals using RASis at baseline was assessed. Inverse probability of treatment weights served to balance more than 70 identified confounders. Marginal structure models were used to estimate per-protocol hazard ratios (HRs). A total of 33 280 individuals (13 633 using GLP-1RAs and 19 647 using DPP-4is; mean [SD] age, 63.7 [12.6] years; 19 853 [59.7%] male) were included. The median (IQR) time receiving treatment was 3.9 (1.0-10.9) months. Compared with DPP-4i use, GLP-1RA use was associated with a lower rate of any hyperkalemia (HR, 0.61; 95% CI, 0.50-0.76) and moderate to severe (HR, 0.52; 95% CI, 0.28-0.84) hyperkalemia. Of 21 751 participants who were using RASis, 1381 discontinued this therapy. The use of GLP-1RAs vs DPP-4is was associated with a lower rate of RASi discontinuation (HR, 0.89; 95% CI, 0.82-0.97). Results were consistent in intention-to-treat analyses and across strata of age, sex, cardiovascular comorbidity, and baseline kidney function. In this study of patients with T2D managed in routine clinical care, the use of GLP-1RAs was associated with lower rates of hyperkalemia and sustained RASi use compared with DPP-4i use. These findings suggest that GLP-1RA treatment may enable wider use of guideline-recommended medications and contribute to clinical outcomes in this population.

Impact of Different Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blocker Resumption Timing on Post Acute Kidney Injury Outcomes

IntroductionEvidence suggests a survival benefit from resuming ACEI/ARB post-AKI compared to non-use, yet the optimal timing and its impact on outcomes are unclear. The risks of earlier resumption, such as recurrent AKI or hyperkalemia, remain unexplored. MethodUsing multi-institutional electronic health records, we analyzed the relationship between three ACEI/ARB resumption timelines post-AKI (prior to discharge, 0-3 months, and 4-6 months post-discharge) and outcomes including all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE), dialysis initiation or end-stage renal disease (ESRD), severe hyperkalemia, and recurrent AKI with hospitalization. Cox proportional models estimated hazard ratios for outcomes across different resumption timings, following a target trial design. ResultsAmong 5,392 AKI survivors resuming ACEI/ARB within 6 months post-AKI, earlier resumption was associated with lower mortality, MACCE, MACCE-related mortality, new dialysis initiation or ESRD (P < 0.001 in trend tests), without increased risks of severe hyperkalemia and re-AKI admissions. Early resumption have a lower mortality compared to 4-6 months post-discharge (before discharge, HR 0.88, 95% CI: 0.83-0.93; 0-3 months, HR 0.89, 95% CI: 0.85 - 0.94). Subgroup analysis showed a lower mortality hazard ratio from earlier resumption among AKI survivors with prior ACEI/ARB comorbidities indications (P < 0.001 in trend tests; before discharge, HR 0.85, 95% CI: 0.80-0.90; 0-3 months, HR 0.88, 95% CI: 0.83 -0.93). ConclusionsOur cohort demonstrates lower risks for mortality, cardiovascular events, and ESRD with early ACEI/ARB resumption, without heightened risks of severe hyperkalemia or rehospitalization for AKI. Early resumption should be considered for patients with indications for ACEI/ARB.

Severe Hyperkalemia Caused by Short-term Indomethacin Therapy in a Patient with Primary Stabbing Headache

Severe Hyperkalemia Caused by Short-term Indomethacin Therapy in a Patient with Primary Stabbing Headache

Rapid and non-invasive diagnosis of hyperkalemia in patients with systolic myocardial failure using a model based on machine learning algorithms.

Hyperkalemia is a potentially life-threatening electrolyte disturbance that if not diagnosed on time may lead to devastating conditions and sudden cardiac death. Blood sampling for potassium level checks is time-consuming and can delay the treatment of severe hyperkalemia on time. So, we propose a non-invasive method for correct and rapid hyperkalemia detection. The cardiac signal of patients referred to the Pediatrics Emergency room of Shahid Rejaee Hospital was measured by a 12-lead Philips electrocardiogram (ECG) device. Immediately, the blood samples of the patients were sent to the laboratory for potassium serum level determination. We defined 16 features for each cardiac signal at lead 2 and extracted them automatically using the algorithm developed. With the help of the principal component analysis (PCA) algorithm, the dimension reduction operation was performed. The algorithms of decision tree (DT), random forest (RF), logistic regression, and support vector machine (SVM) were used to classify serum potassium levels. Finally, we used the receiver operation characteristic (ROC) curve to display the results. In the period of 5 months, 126 patients with a serum level above 4.5 (hyperkalemia) and 152 patients with a serum potassium level below 4.5 (normal potassium) were included in the study. Classification with the help of a RF algorithm has the best result. Accuracy, Precision, Recall, F1, and area under the curve (AUC) of this algorithm are 0.71, 0.87, 0.53, 0.66, and 0.69, respectively. A lead2-based RF classification model may help clinicians to rapidly detect severe dyskalemias as a non-invasive method and prevent life-threatening cardiac conditions due to hyperkalemia.

Beneficial Effect of Calcium Treatment for Hyperkalemia Is Not Due to "Membrane Stabilization".

Hyperkalemia is a common life-threatening condition causing severe electrophysiologic derangements and arrhythmias. The beneficial effects of calcium (Ca 2+ ) treatment for hyperkalemia have been attributed to "membrane stabilization," by restoration of resting membrane potential (RMP). However, the underlying mechanisms remain poorly understood. Our objective was to investigate the mechanisms underlying adverse electrophysiologic effects of hyperkalemia and the therapeutic effects of Ca 2+ treatment. Controlled experimental trial. Laboratory investigation. Canine myocytes and tissue preparations. Optical action potentials and volume averaged electrocardiograms were recorded from the transmural wall of ventricular wedge preparations ( n = 7) at baseline (4 mM potassium), hyperkalemia (8-12 mM), and hyperkalemia + Ca 2+ (3.6 mM). Isolated myocytes were studied during hyperkalemia (8 mM) and after Ca 2+ treatment (6 mM) to determine cellular RMP. Hyperkalemia markedly slowed conduction velocity (CV, by 67% ± 7%; p < 0.001) and homogeneously shortened action potential duration (APD, by 20% ± 10%; p < 0.002). In all preparations, this resulted in QRS widening and the "sine wave" pattern observed in severe hyperkalemia. Ca 2+ treatment restored CV (increase by 44% ± 18%; p < 0.02), resulting in narrowing of the QRS and normalization of the electrocardiogram, but did not restore APD. RMP was significantly elevated by hyperkalemia; however, it was not restored with Ca 2+ treatment suggesting a mechanism unrelated to "membrane stabilization." In addition, the effect of Ca 2+ was attenuated during L-type Ca 2+ channel blockade, suggesting a mechanism related to Ca 2+ -dependent (rather than normally sodium-dependent) conduction. These data suggest that Ca 2+ treatment for hyperkalemia restores conduction through Ca 2+ -dependent propagation, rather than restoration of membrane potential or "membrane stabilization." Our findings provide a mechanistic rationale for Ca 2+ treatment when hyperkalemia produces abnormalities of conduction (i.e., QRS prolongation).

Incidence of hyperkalemia in anuric hemodialysis patients treated with sacubitril/valsartan.

Sacubitril/valsartan is increasingly used in hemodialysis patients due to its cardioprotective benefits. However, its impact on serum potassium levels in anuric patients undergoing hemodialysis remains controversial. We conducted a retrospective data from patients undergoing hemodialysis at two dialysis centers. A total of 71 out of 332 patients receiving hemodialysis treatment were enrolled. Mean serum potassium (mean value of 6-8 determinations), peak serum potassium (maximum K value observed during follow-up observations), and other biochemical parameters were recorded at baseline and during the follow-up period. After 6 months of follow-up, mean serum potassium increased from 4.84 ± 0.45 mmol/L at baseline to 5.07 ± 0.46 mmol/L at 3 months and 5.04 ± 0.46 mmol/L at 6 months (p < 0.001). Notably, no significant group differences were found in peak serum potassium concentrations between baseline and 6 months after sacubitril/valsartan therapy (5.69 ± 0.56 vs. 5.75 ± 0.41, p = 0.419). Prior to starting sacubitril/valsartan treatment, none of the patients had severe hyperkalemia; however, after 3 and 6 months of sacubitril/valsartan therapy, two (2.80%) and three (4.20%) patients experienced severe hyperkalemia, respectively; however, this difference was not statistically significant. Additionally, there was a significant reduction in blood pressure; however, serum sodium, bicarbonate, and Kt/V values did not change significantly during either period. Sacubitril/valsartan therapy is associated with an increase in serum potassium levels in anuric hemodialysis patients. Nevertheless, the proportion of patients with severe hyperkalemia did not increase significantly. This suggests that the use of sacubitril/valsartan in anuric patients on hemodialysis is relatively safe.

Severe respiratory acidosis contributing to refractory hyperkalemia: a case series of COVID-19 patients with renal failure

Introduction: Respiratory acidosis (RA) is not known to cause severe hyperkalemia. However, an exception to this general rule was observed in three patients with severe COVID-19 complicated with renal failure in our center. Objectives: The current study investigated the explanation for hyperkalemia refractory to renal replacement therapy in patients with severe COVID-19 with hypercarbia and renal failure in a tertiary care center. Patients and Methods: In this study, we present a case series of three patients with severe COVID-19 with hypercarbia and dialysis-requiring renal failure who developed persistent hyperkalemia refractory to renal replacement therapy. We studied various causes of persistent hyperkalemia, such as acid‒base disorder, a high turnover state, exogenous administration, rhabdomyolysis, and hypoaldosteronism. Results: All three patients initially presented with episodes of severe hyperkalemia, which were ameliorated after RA was corrected. All of these patients had worsening pulmonary function, after which the hyperkalemia could not be corrected, corresponding to persistent RA. The evidence that there was a contribution of RA to hyperkalemia was further strengthened by the observations of patient 1, in whom the hyperkalemia was only corrected after changing ventilator settings and who was unresponsive to dialysis. We studied the dialysate effluent in patient 3, and the results showed satisfactory removal of potassium with no improvement in the high serum potassium levels. Another interesting finding was that although the dialysate sodium concentration was greater than the serum sodium concentration, there was a decrease in the serum sodium concentration, indicating a reduced movement of sodium into the extracellular space. Conclusion: In our study, metabolic acidosis alone could not explain the high serum potassium levels. Moreover, hyperkalemia was corrected after RA was corrected, indicating that the latter might have been the predominant cause of hyperkalemia in these scenarios. The presence of renal failure and low serum bicarbonate levels might have been the factors contributing to decreased Na+-K+-ATPase activity in the setting of RA, which contributed to severe hyperkalemia in all three patients.