Effectiveness and safety of early treatment with spironolactone for new-onset acute heart failure.

BACKGROUND: The effectiveness and safety of mineralocorticoid receptor antagonists (MRA) in acute heart failure (HF) is uncertain. We sought to describe the prescription of spironolactone during acute HF and whether early treatment is effective and safe in a real-world setting. METHODS: We performed a retrospective cohort study of adult (≥18 years) nonpregnant patients hospitalized with new-onset HF with reduced ejection fraction (HFrEF, defined by ejection fraction ≤40%) within 15 Kaiser Permanente Southern California medical centers between 2016 and 2021. Early treatment was defined by spironolactone prescription at discharge. The primary effectiveness outcome was a composite of HF readmission or all-cause mortality at 180 days. Safety outcomes were hypotension and hyperkalemia at 90 days. RESULTS: Among 2318 HFrEF patients, 368 (15.9%) were treated with spironolactone at discharge. After 1:2 propensity score matching, 354 early treatment and 708 delayed/no treatment patients were included in the analysis. The median age was 63 (IQR: 52-74) years; 61.6% were male, and 38.6% were White. By 90 days, ~20% had crossed over in the two groups. Early treatment was not associated with the composite outcome at 180 days (HR [95% CI]: 0.81 [0.56-1.17]), but a trend towards benefit by 365 days that did not reach statistical significance (0.78 [0.58-1.06]). Early treatment was also associated with hyperkalemia (subdistribution HR [95% CI]: 2.33 [1.30-4.18]) but not hypotension (0.93 [0.51-1.72]). CONCLUSIONS: Early treatment with spironolactone at discharge for new-onset HFrEF in a real-world setting did not reduce the risk of HF readmission or mortality in the first year after discharge. The risk of hyperkalemia was increased.

Cardiovascular and renal safety outcomes of hypoxia-inducible factor prolyl-hydroxylase inhibitor roxadustat for anemia patients with chronic kidney disease: a systematic review and meta-analysis.

This systematic review and meta-analysis were conducted to evaluate the cardiac and kidney-related adverse effects of roxadustat for the treatment of anemia in CKD patients. 18 trials with a total of 8806 participants were identified for analysis. We employed a fixed-effects model for analysis. The pooled result revealed no significant difference in the risk of occurrence of cardiac disorders when comparing CKD patients receiving roxadustat with the placebo (RR = 1.049; CI [0.918 to 1.200]) or ESA (RR = 1.066; CI [0.919 to 1.235]), in both dialysis-dependent (DD) (RR = 1.094; CI [0.925 to 1.293]) or non-dialysis-dependent (NDD) (RR = 1.036; CI [0.916 to 1.171]) CKD patients. No significant difference was observed in the risk of kidney-related adverse events when comparing roxadustat with the placebo (RR = 1.088; CI [0.980 to 1.209]) or ESA (RR = 0.968; CI [0.831 to 1.152]), in DD (RR = 2.649; CI [0.201 to 34.981]) or NDD (RR = 1.053; CI [0.965 to 1.149]) CKD patients. A high risk of hyperkalemia was observed in the roxadustat group in DD (RR = 0.939; CI [0.898 to 0.981]). Incidence of hypertension was higher in the roxadustat for NDD patients (RR = 1.198; CI [1.042 to 1.377]), or compared to the placebo (RR = 1.374; CI [1.153 to 1.638]). In summary, the risk of cardiac or kidney-related events observed in the roxadustat was not significantly increase whether in DD or NDD patients. However, attention must be paid to the occurrence of hyperkalemia for DD patients and hypertension in NDD patients using roxadustat.

Oral potassium poisoning: a retrospective review of the National Poison Data System 2010-2021.

INTRODUCTION: Oral potassium poisoning can be life-threatening. The study aimed to describe patterns of oral potassium poisoning in adult and pediatric populations and characterize its clinical presentation and management as reported by United States poison centers. METHODS: This is a retrospective review of the National Poison Data System from 1 January 2010 through 30 June 2021. We descriptively analyzed cases involving single substance, oral potassium salts. In a second step, we requested a subset of case-specific narratives for cases that resulted in major outcome or death, as well as cases where patients received any of the following therapies: whole bowel irrigation, sodium bicarbonate, calcium, insulin or hemodialysis. We classified hyperkalemia by expected toxicity: mild (peak potassium concentration <6.5 mEq/L), moderate (peak potassium concentration 6.5 to <8 mEq/L) or severe (peak potassium concentration ≥ 8mEq/L). RESULTS: The National Poison Data System included 1,820 cases, 52.3 percent being adults. Among adult cases, 20% (n = 189) resulted in a moderate effect, major effect or death. Among pediatric cases aged <10 years, all exposures were unintentional. Analysis of 49 case narratives showed a median peak potassium concentration of 7.1 mEq/L (interquartile range 5.4-8.6) and a moderate correlation with the dose ingested (r = 0.66). Severe hyperkalemia was associated with QRS complex widening (P < 0.001), peaked T-waves (P = 0.001), and neurological symptoms (P = 0.04). Whole bowel irrigation was associated with mild hyperkalemia (P = 0.011), and hemodialysis was associated with severe hyperkalemia (P < 0.001). DISCUSSION: Analysis of data showed that therapy to promote intracellular shift of potassium is the mainstay of management of oral potassium poisoning, followed by hemodialysis. LIMITATIONS: Poison center data are susceptible to reporting bias. National Poison Data System data are affected by completeness and accuracy of reporting from health care providers and the lay public. CONCLUSIONS: Single substance, oral potassium poisoning, reported to United States poison centers, is mostly unintentional and rarely results in hyperkalemia.

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).

Combination Therapy Use and Associated Events in Clinical Practice Following Dissemination of Trial Findings: A De-Implementation Study Using Interrupted Time Series Analysis.

PURPOSE: It takes 17 years, on average, for trial results to be implemented into practice. Using data from the Department of Veterans Affairs (VA), this study assessed the potential impact on clinical practice of the dissemination of findings from a randomized, controlled trial reporting harm with the use of combination therapy. Communication between research and VA Pharmacy Benefits Management Services (PBM)  provided the impetus for communication from the PBM about the findings of the trial in accordance with policy. METHODS: In this de-implementation study, interrupted time series analysis was used for assessing prescribing patterns and adverse clinical events before and after the dissemination of the trial findings. The de-implementation strategy was multicomponent and multilevel. Strategies were aligned with categories outlined in the Expert Recommendations for Implementing Change: train and educate stakeholders, use evaluative and iterative strategies, develop stakeholder inter-relationships, change infrastructure, provide interactive assistance, and engage consumers. VA patients with type 2 diabetes mellitus, chronic kidney disease stages 1 to 3, and a moderate or severe albuminuria who received care between July 2008 and November 2017 were included. Patients were subgrouped according to treatment with an angiotensin-converting enzyme inhibitor + angiotensin receptor blocker. The primary end point was the prevalence of combination therapy use. Secondary end points were the incidences of acute kidney injury and hyperkalemia. FINDINGS: This study followed 712,245 patients, 9297 of whom used combination therapy. Data were available from 428,535 and 283,710 patients pre- and post-intervention, respectively; among these, 8324 and 973 patients used combination therapy, the median ages were 66 and 68 years, and 96.92% and 98.82% were men. One month following communication from the PBM, the reductions in combination therapy users, acute kidney injury events, and hyperkalemia were 331.94 (95% CI, 500.27-163.32), 36.58% (95% CI, 31.90%-41.95%), and 25.49% (95% CI, 14.17%-36.07%) per 100,000 patients per month, respectively (all, P < 0.001), whereas before the communication, these changes were +14.84 (95% CI, 10.27-19.42), -3.46% (95% CI, 3.18-3.74), and -3.27% (95% CI, 2.66%-3.87%) (all, P < 0.001). IMPLICATIONS: The apparent speed and impact of the implementation of changes resulting from the dissemination of trial findings into VA clinical practice are encouraging. The speed of implementation was much faster than average for health care providers in the United States. Established communications between research and clinical practice, as well as established policy and communications between PBM and clinical practice, may be a model for other health care organizations.

The real-world safety of sacubitril / valsartan among older adults (≥75): A pharmacovigilance study from the FDA data.

BACKGROUND: Heart failure is a major cause of morbidity and mortality among older adults. Sacubitril-Valsartan (Sac/Val) has been shown to improve patients' outcomes; however, its safety profile among older adults has not been adequately examined. We therefore aimed to examine its safety profile among this population. METHODS: We conducted a retrospective pharmacovigilance study utilizing the FDA's database of safety reports (FAERS). We employed disproportionality analysis comparing Sac/Val to angiotensin receptor blockers (ARBs). We aim to evaluate the reporting of pre-defined adverse events associated with Sac/Val (hypotension, acute kidney injury (AKI), hyperkalemia and angioedema) in two age groups: adults (< 75 years) and older adults (≥ 75). For each subgroup, we calculated reporting odds ratio (ROR) and compared them by calculating P for interaction. RESULTS: The FAERS database encompassed 18,432 unique reports of Sac/Val. Of them, 12,630 (68.5%) subjects were adults (< 75 years), and 5802 (31.5%) were older adults (≥ 75 years), with a median age (IQR) of 68 (59-77). When compared to ARBs, Sac/Val was associated with higher reporting of hypotension, lower reporting of acute kidney injury (AKI) and hyperkalemia, and similar reporting of angioedema. Notably, we did not observe a significant interaction between the age subgroups and the risk estimates (AKI: Pinteraction = 0.72, hyperkalemia: Pinteraction = 0.94, hypotension: Pinteraction = 0.31, and angioedema: Pinteraction = 0.61). CONCLUSIONS: In this postmarking study, none of the prespecified adverse events was reported more frequently in older adults. These findings provide reassurance for safety use of Sac/Val in older adults.

Adverse effects of sodium-glucose cotransporter-2 inhibitors in patients with heart failure: a systematic review and meta-analysis.

Sodium-glucose cotransoporter-2 inhibitors (SGLT-2Is) improve prognosis in heart failure (HF) patients both with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). However, these drugs can have some side effects. To estimate the relative risk of side effects in HF patients treated with SGLT-2Is irrespective from left ventricular EF and setting (chronic and non-chronic HF). Five randomized controlled trials (RCTs) enrolling patients with HFrEF, 4 RCTs enrolling non-chronic HF, and 3 RCTs enrolling HFpEF were included. Among side effects, urinary infection, genital infection, acute kidney injury, diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations were considered in the analysis. Overall, 24,055 patients were included in the analysis: 9020 (38%) patients with HFrEF, 12,562 (52%) with HFpEF, and 2473 (10%) with non-chronic HF. There were no differences between SGLT-2Is and placebo in the risk to develop diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations. HFrEF patients treated with SGLT-2Is had a significant reduction of acute kidney injury (RR = 0.54 (95% CI 0.33-0.87), p = 0.011), whereas no differences have been reported in the HFpEF group (RR = 0.94 (95% CI 0.83-1.07), p = 0.348) and non-chronic HF setting (RR = 0.79 (95% CI 0.55-1.15), p = 0.214). A higher risk to develop genital infection (overall 2.57 (95% CI 1.82-3.63), p < 0.001) was found among patients treated with SGLT-2Is irrespective from EF (HFrEF: RR = 1.96 (95% CI 1.17-3.29), p = 0.011; HFpEF: RR = 3.04 (95% CI 1.88-4.90), p < 0.001). The risk to develop urinary infections was increased among SGLT-2I users in the overall population (RR = 1.13 (95% CI 1.00-1.28), p = 0.046) and in the HFpEF setting (RR = 1.19 (95% CI 1.02-1.38), p = 0.029), whereas no differences have been reported in HFrEF (RR = 1.05 (95% CI 0.81-1.36), p = 0.725) and in non-chronic HF setting (RR = 1.04 (95% CI 0.75-1.46), p = 0.806). SGLT-2Is increase the risk of urinary and genital infections in HF patients. In HFpEF patients, the treatment increases the risk of urinary infections compared to placebo, whereas SGLT-2Is reduce the risk of acute kidney disease in patients with HFrEF.

Effects of Mineralocorticoid Receptor Antagonists for Chronic Kidney Disease: A Systemic Review and Meta-Analysis.

BACKGROUND: Mineralocorticoid receptor blockade could be a potential approach for the inhibition of chronic kidney disease (CKD) progression. The benefits and harms of different mineralocorticoid receptor antagonists (MRAs) in CKD are inconsistent. OBJECTIVES: The aim of the study was to summarize the benefits and harms of MRAs for CKD patients. METHODS: We searched MEDLINE, EMBASE, and the Cochrane databases for trials assessing the effects of MRAs on non-dialysis-dependent CKD populations. Treatment and adverse effects were summarized using meta-analysis. RESULTS: Fifty-three trials with 6 different MRAs involving 22,792 participants were included. Compared with the control group, MRAs reduced urinary albumin-to-creatinine ratio (weighted mean difference [WMD], -90.90 mg/g, 95% CI, -140.17 to -41.64 mg/g), 24-h urinary protein excretion (WMD, -0.20 g, 95% CI, -0.28 to -0.12 g), estimated glomerular filtration rate (eGFR) (WMD, -1.99 mL/min/1.73 m2, 95% CI, -3.28 to -0.70 mL/min/1.73 m2), chronic renal failure events (RR, 0.86, 95% CI, 0.79-0.93), and cardiovascular events (RR, 0.84, 95% CI, 0.77-0.92). MRAs increased the incidence of hyperkalemia (RR, 2.04, 95% CI, 1.73-2.40) and hypotension (RR, 1.80, 95% CI, 1.41-2.31). MRAs reduced the incidence of peripheral edema (RR, 0.65, 95% CI, 0.56-0.75) but not the risk of acute kidney injury (RR, 0.94, 95% CI, 0.79-1.13). Nonsteroidal MRAs (RR, 0.66, 95% CI, 0.57-0.75) but not steroidal MRAs (RR, 0.20, 95% CI, 0.02-1.68) significantly reduced the risk of peripheral edema. Steroidal MRAs (RR, 5.68, 95% CI, 1.26-25.67) but not nonsteroidal MRAs (RR, 0.52, 95% CI, 0.22-1.22) increased the risk of breast disorders. CONCLUSIONS: In the CKD patients, MRAs, particularly in combination with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, reduced albuminuria/proteinuria, eGFR, and the incidence of chronic renal failure, cardiovascular and peripheral edema events, whereas increasing the incidence of hyperkalemia and hypotension, without the augment of acute kidney injury events. Nonsteroidal MRAs were superior in the reduction of more albuminuria with fewer peripheral edema events and without the augment of breast disorder events.

A population-based cohort defined risk of hyperkalemia after initiating SGLT-2 inhibitors, GLP1 receptor agonists or DPP-4 inhibitors to patients with chronic kidney disease and type 2 diabetes.

Hyperkalemia is a common adverse event in patients with chronic kidney disease (CKD) and type 2 diabetes and limits the use of guideline-recommended therapies such as renin-angiotensin system inhibitors. Here, we evaluated the comparative effects of sodium-glucose cotransporter-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) on the risk of hyperkalemia. We conducted a population-based active-comparator, new-user cohort study using claims data from Medicare and two large United States commercial insurance databases (April 2013-April 2022). People with CKD stages 3-4 and type 2 diabetes who newly initiated SGLT-2i vs. DPP-4i (141671 patients), GLP-1RA vs. DPP-4i (159545 patients) and SGLT-2i vs. GLP-1RA (93033 patients) were included. The primary outcome was hyperkalemia diagnosed in inpatient or outpatient settings. Secondary outcomes included hyperkalemia diagnosed in inpatient or emergency department setting, and serum potassium levels of 5.5 mmol/L or more. Pooled hazard ratios and rate differences were estimated after propensity score matching to adjust for over 140 potential confounders. Initiation of SGLT-2i was associated with a lower risk of hyperkalemia compared with DPP-4i (hazard ratio 0.74; 95% confidence interval 0.68-0.80) and contrasted to GLP-1RA (0.92; 0.86-0.99). Compared with DPP-4i, GLP-1RA were also associated with a lower risk of hyperkalemia (0.80; 0.75-0.86). Corresponding absolute rate differences/1000 person-years were -24.8 (95% confidence interval -31.8 to -17.7), -5.0 (-10.9 to 0.8), and -17.7 (-23.4 to -12.1), respectively. Similar findings were observed for the secondary outcomes, among subgroups, and across single agents within the SGLT-2i and GLP-1RA classes. Thus, SGLT-2i and GLP-1RA are associated with a lower risk of hyperkalemia than DPP-4i in patients with CKD and type 2 diabetes, further supporting the use of these drugs in this population.

Mineralocorticoid receptor antagonist treatment in patients with renal insufficiency and the associated risk of hyperkalemia and death.

OBJECTIVES: Mineralocorticoid receptor antagonist (MRA) treatment is kidney protective but not recommended to patients with advanced renal failure due to the risk of hyperkalemia and death. This study aimed to examine the impact of MRA treatment in patients with chronic kidney disease on risk of hyperkalemia and subsequent mortality. METHODS: Rates of hyperkalemia were compared across strata of estimated glomerular filtration rate (eGFR) and MRA treatment based on cox regression using a nested case-control framework with 1 : 4 matching of patients with hyperkalemia (K + ≥6.0 mmol/l) with controls from the Danish general population on age, sex, diabetes, and hypertension. Risk of subsequent 30-day mortality was assessed in a cohort study with comparisons across strata of eGFR and MRA treatment based on multiple Cox regression. RESULTS: Thirty-two thousand four hundred twenty-six cases with hyperkalemia were matched with 127 038 controls. MRA treatment was associated with an increased rate of hyperkalemia with hazard ratios [95% confidence interval (95% CI)] of 8.28 (7.78-8.81), 5.12 (4.67-5.62), 3.58 (3.23-3.97), and 1.89 (1.60-2.23) in patients with eGFR at least 60, 45-59, 30-44, and less than 30 ml/min/1.73 m 2 , respectively (Reference: No MRA).However, MRA-exposed patients had a lower 30-day mortality risk following hyperkalemia with absolute risks (95% CI) of 29.3% (27.8-31.1), 20.3% (18.7-22.4), 19.5% (17.9-21.7), and 19.7% (17.4-22.5) compared to 39.8% (38.8-40.8), 32.0% (30.7-33.1), 28.8% (27.5-31.2), and 22.5% (21.4-23.4) in patients without MRA exposure in patients with GFR at least 60, 45-59, 30-44, and less than 30 ml/min/1.7 3m 2 , respectively. CONCLUSION: MRA treatment was associated with an increased rate of hyperkalemia but decreased risk of subsequent 30-day mortality across all stages of renal impairment.

Association of serum potassium level with dietary potassium intake in Chinese older adults: a multicentre, cross-sectional survey.

OBJECTIVES: Evidence linking dietary potassium and serum potassium is virtually scarce and inconclusive. The aim of the study was to investigate the association between serum potassium level and potassium intake measured by 24-hour urine. We also explored whether the association differed across health conditions. DESIGN: A cross-sectional study conducted from September 2017 to March 2018. SETTING: 48 residential elderly care facilities in northern China. PARTICIPANTS: Participants aged 55 years and older and with both serum potassium and 24-hour urinary potassium measured were classified as having a low (apparently healthy), moderate (with ≥1 health condition but normal renal function) and high (with ≥1 health condition and abnormal renal function) risk of hyperkalaemia. EXPOSURE: Potassium intake is measured by 24-hour urinary potassium. OUTCOMES: Serum potassium in association with potassium intake after adjustment for age, sex, region and accounting for the cluster effect. RESULTS: Of 962 eligible participants (mean age 69.1 years, 86.8% men), 17.3% were at low risk, 48.4% at moderate risk and 34.3% at high risk of hyperkalaemia. Serum potassium was weakly associated with 24-hour urinary potassium among individuals with moderate (adjusted ß=0.0040/L; p=0.017) and high (adjusted ß=0.0078/L; p=0.003) but not low (adjusted ß=0.0018/L; p=0.311) risk of hyperkalaemia. CONCLUSIONS: A weak association between dietary potassium intake and serum potassium level existed only among individuals with impaired renal function or other health conditions but not among apparently healthy individuals. The results imply that increasing dietary potassium intake may slightly increase the risk of hyperkalaemia but may also decrease the risk of hypokalaemia in unhealthy individuals, both of which have important health concerns. TRIAL REGISTRATION NUMBER: NCT03290716; Post-results.

[Hyperkaliemia in hypertensive patients : more than a coincidence?] / Hyperkaliémie chez le patient hypertendu : plus qu'une coïncidence ?

Hyperkaliemia is a relatively common electrolyte disorder whose manifestations and consequences can be serious if severe hyperkalemia is not treated. In the context of hypertension, it is important to look for co-morbidities and conditions favoring hyperkaliemia, to review the drugs prescribed that could contribute to potassium elevation and to bear in mind that when the common causes have been excluded, a genetic origin may be present. In this article, the focus is on the association of hypertension and hyperkaliemia, in the context of the marketing of new cardiovascular and renal drugs that may induce this electrolyte disorder.

L'hyperkaliémie représente un trouble électrolytique relativement fréquent dont les manifestations et conséquences peuvent être graves si l'hyperkaliémie sévère n'est pas corrigée. Dans le contexte d'une hypertension, il faut rechercher les comorbidités et les conditions favorisant l'hyperkaliémie, revoir les médicaments prescrits qui pourraient contribuer à l'élévation du potassium et garder en mémoire que lorsque les causes fréquentes ont été exclues, une origine génétique peut être présente. Dans cet article, l'accent est mis sur l'association de l'hypertension et l'hyperkaliémie, dans le contexte de la mise sur le marché de nouveaux médicaments dans les domaines cardiovasculaire et rénal qui pourraient favoriser la survenue de ce trouble électrolytique.

Multicentre, observational, retrospective cohort of hyperkalaemia burden at haemodialysis facility-level in China: the Visualize-HD study protocol.

OBJECTIVES: Hyperkalaemia is a potentially life-threatening disorder in patients undergoing haemodialysis (HD). Excess mortality and hospitalisation have been associated with hyperkalaemia (HK) after the long (2-day) interdialytic interval (LIDI) in patients on thrice a week HD compared with the short (1-day) interdialytic interval. Moreover, not much research has been conducted in China on the descriptive epidemiology and management of HK among different HD centres. The aim of this study is to address this evidence gap by investigating the risk factors associated with HK clinical burden at the HD facility level, current HD centres management patterns, serum potassium management patterns, as well as the risk factors associated with crude mortality in China. DESIGN: Multicentre, observational, retrospective cohort study. SETTING: This study plans to enrol 300 HD centres across China. Haemodialysis centres having ≥100 patients on maintenance HD within 3 years before study initiation, with participation willingness, routine blood collection post-LIDI and death records will be included. PARTICIPANTS: Patients aged ≥18 years and on chronic HD for ≥3 months will be considered eligible. Summary data about serum potassium, characteristics of patients, facility practice patterns will be collected at HD facility level and death records will be at the patient level. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome will be to examine the association between suspected risk factors and HK prevalence at HD facility level. Suspected risk factors include dialysis prescriptions and serum potassium testing frequency, characteristics of patients and related medication usage. The secondary outcome will be to determine the HK prevalence, serum potassium management pattern and risk factors associated with crude mortality. The primary and secondary outcomes will be analysed using regression models. Exploratory outcomes will further investigate the risk factors associated with serum potassium ≥6.0 and ≥6.5 mmol/L. CONCLUSION: The study is expected to provide insights to improve dialysis practice patterns and understand the clinical burden of HK. ETHICS AND DISSEMINATION: This study protocol was reviewed and approved by the Institutional Review Boards and Ethics Committee of Peking University People's Hospital (Approval number: 2020PHB324-01). The results will be disseminated through national and international presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05020717.

Clinical outcomes by serum potassium levels for patients hospitalized for heart failure: Secondary analysis of data from the China National Heart Failure Registry.

BACKGROUND: Dyskalemia is a mortality risk factor in patients with heart failure (HF). HYPOTHESIS: We described the prevalence of dyskalemia, and clinical outcomes by serum potassium (sK) levels, in Chinese patients hospitalized for HF. METHODS: In this secondary analysis of the prospective China National Heart Failure Registry, adult patients hospitalized between January 1, 2013 and June 30, 2015 who had at least one baseline sK measurement were followed for up to 3 years after discharge. The use of renin-angiotensin-aldosterone system inhibitors at baseline and clinical outcomes during follow-up were compared among sK groups. RESULTS: Among 6950 patients, 5529 (79.6%) had normokalemia (sK >3.5-5.0 mmol/L), 1113 (16.0%) had hypokalemia (sK 0-3.5 mmol/L), and 308 (4.4%) had hyperkalemia (sK >5.0 mmol/L). Baseline characteristics that were most common in patients with hyperkalemia than those with hypo- and normokalemia included older age, HF with reduced ejection fraction, New York Heart Association Class III/IV status, hypertension, and chronic kidney disease. Use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) differed across sK groups (p = .0001); reported in 64.1%, 63.4%, and 54.5% of patients with hypo-, normo-, and hyperkalemia, respectively. Overall, 26.6%, 28.6%, and 36.0% of patients with hypo-, normo-, and hyperkalemia had rehospitalization for worsened HF, or cardiovascular mortality; p = .0057 for between-group comparison. CONCLUSIONS: Patients with hyperkalemia received ACEIs or ARBs for HF treatment at baseline less frequently than those with hypo- or normokalemia, and had worse prognoses. This warrants further investigation into effective hyperkalemia management in HF.

Hyperkalaemia prevalence and dialysis patterns in Chinese patients on haemodialysis: an interim analysis of a prospective cohort study (PRECEDE-K).

BACKGROUND: Hyperkalaemia is a known risk factor for cardiac arrhythmia and mortality in patients on haemodialysis. Despite standard adequate haemodialysis, hyperkalaemia is common in patients with end-stage renal disease (ESRD) at interdialytic intervals. Data on hyperkalaemia burden and its effects on dialysis patterns and serum potassium (sK) fluctuations in patients on haemodialysis in China remain limited. The prospective, observational cohort study (PRECEDE-K; NCT04799067) investigated the prevalence, recurrence, and treatment patterns of hyperkalaemia in Chinese patients with ESRD on haemodialysis. METHODS: Six hundred adult patients were consecutively enrolled from 15 secondary and tertiary hospitals in China. In this interim analysis, we report the baseline characteristics of the cohort, the prevalence of predialysis hyperkalaemia (sK > 5.0 mmol/L), and the trends in serum-dialysate potassium gradient and intradialytic sK shift at Visit 1 (following a long interdialytic interval [LIDI]). RESULTS: At baseline, most patients (85.6%) received three-times weekly dialysis; mean duration was 4.0 h. Mean urea reduction ratio was 68.0% and Kt/V was 1.45; 60.0% of patients had prior hyperkalaemia (previous 6 months). At Visit 1, mean predialysis sK was 4.83 mmol/L, and 39.6% of patients had hyperkalaemia. Most patients (97.7%) received a dialysate potassium concentration of 2.0 mmol/L. The serum-dialysate potassium gradient was greater than 3 mmol/L for over 40% of the cohort (1- < 2, 2- < 3, 3- < 4, and ≥ 4 mmol/L in 13.6%, 45.1%, 35.7%, and 5.2% of patients, respectively; mean: 2.8 mmol/L). The intradialytic sK reduction was 1- < 3 mmol/L for most patients (0- < 1, 1- < 2, 2- < 3, and ≥ 3 mmol/L in 24.2%, 62.2%, 12.8%, and 0.9% of patients, respectively; mean: 1.4 mmol/L). CONCLUSIONS: Hyperkalaemia after a LIDI was common in this real-world cohort of Chinese patients despite standard adequate haemodialysis, and led to large serum-dialysate potassium gradients and intradialytic sK shifts. Previous studies have shown hyperkalaemia and sK fluctuations are highly correlated with poor prognosis. Effective potassium-lowering treatments should be evaluated for the improvement of long-term prognosis through the control of hyperkalaemia and sK fluctuations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04799067.

Neonatal hyperkalemia associated with maternal ritodrine: A retrospective study.

BACKGROUND: We recently reported on a late preterm infant born at 36 weeks' gestation with serious arrhythmia due to hyperkalemia associated with long-term maternal ritodrine administration. It is unknown whether ritodrine alone increases the risk of neonatal hyperkalemia in infants born at 34-36 weeks' gestation. METHODS: This single-center, retrospective, cohort study enrolled late preterm infants (34-36 gestational weeks) born between 2004 and 2018. Cases with maternal magnesium sulfate use were not sufficient for statistical analysis and so were excluded from the study. Risk factors for the occurrence of hyperkalemia were determined based on clinical relevance and previous reports. RESULTS: In all, 212 late preterm infants with maternal ritodrine use and 400 infants without tocolysis were included in the study. Neonatal hyperkalemia occurred in 5.7% (12/212) in the ritodrine group and 1.8% (7/400) in the control group. The risk of neonatal hyperkalemia was significantly increased by maternal ritodrine administration with a crude odds ratio (OR) of 3.37 (95% confidence interval [CI]: 1.30-8.69; p < 0.01) and an adjusted OR of 3.71 (95% CI: 1.41-9.74; p < 0.01) on multivariable analysis. Long-term tocolysis (≥28 days) with ritodrine increased the risk of neonatal hyperkalemia with 9.3% (11/118) of infants developing hyperkalemia (adjusted OR 4.86; 95% CI: 1.59-14.83; p < 0.01). Neonatal hyperkalemia was not found within 2 weeks of ritodrine administration. CONCLUSION: This research suggests that late preterm infants born after long-term ritodrine administration are at risk of neonatal hyperkalemia and require special attention.

Prolonged postoperative hypoaldosteronism related to hyperkalemia in patients with aldosterone-producing adenoma.

Hyperkalemia is developed in a part of patients with aldosterone-producing adenoma (APA) after adrenalectomy, suspected to be due to the insufficiency of aldosterone secretion. The purpose of this study is to determine the frequency and characteristics of prolonged postoperative hypoaldosteronism (PPHA) using chemiluminescent enzyme immunoassay (CLEIA). We studied 58 patients with APA with long time after adrenalectomy and whose PAC was measured using a CLEIA kit. The PAC value measured using CLEIA was significantly lower than that of using RIA between two consecutive visits before and after the shift of measuring method of PAC (median [interquantile range], 123.0 [99.8-164.0] vs. 39.5 [15.8-64.2] pg/mL, p < 0.01). PAC was below the minimum limit of quantification (4.0 pg/mL) of the CLEIA kit at least once in nine patients (15.5%) who had PPHA. The PPHA group were older (mean ± standard deviation, 61.3 ± 8.5 vs. 50.5 ± 10.1 years, p < 0.01) and had lower eGFR (60.3 ± 14.0 vs. 82.3 ± 22.8 mL/min/1.73 m2, p < 0.01) than the non-PPHA group. The frequency of postoperative hyperkalemia (maximum serum potassium >5.5 mEq/L) was higher in the PPHA group than in the non-PPHA group (55.6% vs. 8.2%, p < 0.01). In conclusion, a few patients with APA long time after adrenalectomy had unmeasurable PAC using CLEIA. PPHA is likely to develop in patients with APA after adrenalectomy who are older and have impaired renal function. Additionally, PPHA is related to the occurrence of postoperative hyperkalemia.

Short-term prognosis of changes in plasma potassium following an episode of hyperkalaemia in patients with chronic heart failure.

BACKGROUND/AIM: There is an increasing prevalence of chronic heart failure (HF). It is well known that patients with HF and disturbances in the potassium level have an increased mortality risk. The aim of this study was to investigate the prognosis of a second plasma-potassium measurement after an episode with hyperkalaemia on short-term mortality in patients with chronic HF. METHODS AND RESULTS: From Danish national registers, 2,339 patients with chronic HF and hyperkalaemia (>4.6 mmol/L) at first potassium measurement within 14-365 days from concomitant treatment were identified. To be included, a second measurement was required within 6-30 days subsequent to the first measurement and the 60-day mortality was observed. Based on the second measurement, the patients were divided into five groups: <3.5 mmol/L (n = 257), 3.5-4.0 mmol/L (n = 709), 4.1-4.6 mmol/L (n = 1,204, reference), 4.7-5.0 mmol/L (n = 89) and >5.0 mmol/L (n = 80). To assess all-cause and cardiovascular mortality, we used the Cox regression model. The multivariable analysis showed that patients with potassium concentrations <3.5 mmol/L (hazard ratio (HR): 3.03; 95% CI: 2.49-3.70) and 3.5-4.0 mmol/L (HR: 1.81; 95% CI: 1.54-2.14) had a worse prognosis compared to the reference. We observed similar results when calculating the risk of cardiovascular mortality. A restricted cubic spline curve showed a U-shaped relationship between plasma-potassium and all-cause mortality. CONCLUSION: Patients with chronic HF and hyperkalaemia who became hypokalaemic after 6-30 days were associated with a higher 60-day all-cause and cardiovascular mortality compared to the reference. This also applied for patients with low normal potassium concentrations (3.5-4.0 mmol/L).

Pseudohyperkalemia in chronic lymphocytic leukemia: Prevalence, impact, and management challenges.

The term pseudohyperkalemia refers to a false elevation in serum potassium levels due to potassium release from cells in vitro. Falsely elevated potassium levels have been reported in patients with thrombocytosis, leukocytosis, and hematologic malignancies. This phenomenon has been particularly described in chronic lymphocytic leukemia (CLL). Leukocyte fragility, extremely high leukocyte counts, mechanical stress, higher cell membrane permeability related to an interaction with lithium heparin in plasma blood samples, and metabolite depletion due to a high leukocyte burden have been reported to contribute to pseudohyperkalemia in CLL. The prevalence of pseudohyperkalemia is up to 40%, particularly in the presence of a high leukocyte count (>50 × 109/L). The diagnosis of pseudohyperkalemia is often overlooked, which may result in unnecessary and potentially harmful treatment. The use of whole blood testing and point-of-care blood gas analysis, along with thorough clinical evaluation, may help differentiate between true and pseudohyperkalemic episodes.

Effect of end-stage kidney disease on the return of spontaneous circulation in Taiwanese adults with out-of-hospital cardiac arrest.

Rescuing patients with out-of-hospital cardiac arrest (OHCA), especially those with end-stage kidney disease (ESKD), is challenging. This study hypothesizes that OHCA patients with ESKD undergoing maintenance hemodialysis have (1) higher rates of return of spontaneous circulation (ROSC) during cardio-pulmonary resuscitation (CPR) and (2) lower rates of hyperkalemia and less severe acidosis than those without ESKD. OHCA patients who received CPR between 2011 and 2020 were dichotomized into ESKD and non-ESKD groups. The association of ESKD with "any" and "sustained" ROSC were examined using logistic regression analysis. Furthermore, the effect of ESKD on hospital outcomes for OHCA patients who survived to admission was evaluated using Kaplan-Meier analysis. ESKD patients without "any" ROSC displayed lower potassium and higher pH levels than non-ESKD patients. ESKD was positively associated with "any" ROSC (adjusted-OR: 4.82, 95% CI 2.70-5.16, P < 0.01) and "sustained" ROSC (adjusted-OR: 9.45, 95% CI 3.83-24.13, P < 0.01). Kaplan-Meier analysis demonstrated ESKD patients had a non-inferior hospital survival than non-ESKD patients. OHCA patients with ESKD had lower serum potassium level and less severe acidosis compared to the general population in Taiwan; therefore, should not be treated under the stereotypical assumption that hyperkalemia and acidosis always occur.