PROphylaxis for paTiEnts at risk of COVID-19 infecTion (PROTECT-V).

BACKGROUND: Despite the introduction of vaccination, there remains a need for pre-exposure prophylactic agents against SARS-CoV-2. Several patient groups are more vulnerable to SARS-CoV-2 infection by virtue of underlying health conditions, treatments received or suboptimal responses to vaccination. METHODS: PROTECT-V is a platform trial testing pre-exposure prophylactic interventions against SARS-CoV-2 infection in vulnerable patient populations (organ transplant recipients; individuals with oncological/haematological diagnoses, immune deficiency or autoimmune diseases requiring immunosuppression or on dialysis). Multiple agents can be evaluated across multiple vulnerable populations sharing placebo groups, with the option of adding additional treatments at later time points as these become available. The primary endpoint is symptomatic SARS-CoV-2 infection, and each agent will be independently evaluated in real time when the required number of events occurs. Presently, three agents are approved in the platform: intranasal niclosamide, nasal and inhaled ciclesonide and intravenous sotrovimab. DISCUSSION: Despite the introduction of vaccination, there remains a need for pre-exposure prophylactic agents against SARS-CoV-2. Several patient groups are more vulnerable to COVID-19 disease by virtue of underlying health conditions, treatments received or suboptimal responses to vaccination. TRIAL REGISTRATION: ClinicalTrials.gov NCT04870333. EudraCT 2020-004144-28.

NEPHwork: creating a quality improvement and research network for UK renal trainees.

NEPHwork was established in 2020 as a renal specialty trainee-driven national quality improvement and research network with the aim of coupling the benefits of trainee-led collaboration with the rich data collection infrastructure established by the UK renal registry. NEPHwork was established to support the development, coordination and delivery of audit and research projects by renal trainees on a national scale. The first collaborative project centred on the compliance with care quality standards in managing acute kidney injury. The project enabled a large amount of data to be collected over a relatively short period of time and allowed comparison between renal units involved in contributing to the data. The initiation of the NEPHwork collaboration had to overcome delays and service pressure related to the COVID-19 pandemic. Furthermore, the method of linkage analysis used in the data collection and lack of cohesion with regional information technology (IT) services prevented trainees from certain regions from contributing to the project and this is a key priority for the next NEPHwork collaboration.

Hypoglycaemia due to insulin therapy for the management of hyperkalaemia in hospitalised adults: A scoping review.

INTRODUCTION: Hyperkalaemia is a very common electrolyte disorder encountered in hospitalised patients. Although hypoglycaemia is a frequent complication of insulin therapy, it is often under-appreciated. We conducted a scoping review of this important complication, and of other adverse effects, of the treatment of hyperkalaemia in hospitalised adults to map existing research on this topic and to identify any knowledge gaps. MATERIALS AND METHODS: We followed the PRISMA-ScR guidelines. Studies were eligible for inclusion if they reported on any adverse effects in hospitalised patients ≥18-years-old, with hyperkalaemia receiving treatment that included insulin. All eligible research from 1980 to 12 October 2021 were included. We searched Medline (PubMed), Embase (Ovid), the Cochrane Library, CINHAL, Africa-Wide Information, Web of Science Core Collection, LILACS and Epistemonikos. The protocol was prospectively registered with the Open Science Framework (https://osf.io/x8cs9). RESULTS: Sixty-two articles were included. The prevalence of hypoglycaemia by any definition was 17.2% (95% CI 16.6-17.8%). The median timing of hypoglycaemia was 124 minutes after insulin administration (IQR 102-168 minutes). There were no differences in the prevalence of hypoglycaemia when comparing insulin dose (<10 units vs. ≥10 units), rate of insulin administration (continuous vs. bolus), type of insulin (regular vs. short-acting) or timing of insulin administration relative to dextrose. However, lower insulin doses were associated with a reduced prevalence of severe hypoglycaemia (3.5% vs. 5.9%, P = 0.02). There was no difference regarding prevalence of hypoglycaemia by dextrose dose (≤25 g vs. >25 g); however, prevalence was lower when dextrose was administered as a continuous infusion compared with bolus administration (3.3% vs. 19.5%, P = 0.02). The most common predictor of hypoglycaemia was the pre-treatment serum glucose concentration (n = 13 studies), which ranged from < 5.6-7.8 mmol/L. CONCLUSION: This is the first comprehensive review of the adverse effects following insulin therapy for hyperkalaemia. Hypoglycaemia remains a common adverse effect in hospitalised adults. Future randomised trials should focus on identifying the optimal regimen of insulin therapy to mitigate the risk of hypoglycaemia.

How common is hyperkalaemia? A systematic review and meta-analysis of the prevalence and incidence of hyperkalaemia reported in observational studies.

Background: The prevalence and incidence of hyperkalaemia, a potassium abnormality that can potentially have life-threatening consequences, are unclear. Methods: The objective was to provide the most comprehensive overview of the epidemiology of hyperkalaemia to date within the general population, across different continents, in different healthcare settings and within pre-specified subgroups. Embase and MEDLINE were searched from database inception to 2 February 2021 using the Ovid SP platform. Relevant congress proceedings from 2018 to 2020 were also reviewed for inclusion. There was no language constraint applied. Observational studies from any time period and language reporting prevalence or incidence of hyperkalaemia within both adult and paediatric populations. Four investigators independently screened abstracts and assessed study quality of those meeting the pre-determined inclusion/exclusion criteria. Data extraction was conducted by the lead author with oversight from the senior author and data were pooled using a random-effects model. The measures assessed were the prevalence and incidence of hyperkalaemia. Prevalence was reported as a percentage, whilst incidence was reported as the rate per 100 person years. Results: In total, 542 articles were included from an initial search of 14 112 articles. Across all adult studies, we report a prevalence of hyperkalaemia (by any definition/threshold) of 6.3% [95% confidence interval (CI): 5.8-6.8%], with an incidence of hyperkalaemia in the adult population of 2.8 (2.3-3.3) cases per 100 person years. Prevalence within the general population was 1.3% (1.0-1.8%), whilst incidence was 0.4 (0.2-0.8) cases per 100 person years. There was a variation by sex with a prevalence of 6.3% (4.9-8.0%) in males and 5.1% (4.0-6.6%) in females. Prevalence also varied according to the definition/threshold of hyperkalaemia used: >5 mmol/L-8.0% (7.2-8.9), ≥5.5 mmol/L-5.9% (3.5-10.0) and ≥6.0 mmol/L-1.0% (0.8-1.4); hyperkalaemia (by any definition/threshold) was highest amongst patients with end-stage kidney disease (21.5%; 18.3-25.3), kidney transplant patients (21.8%; 16.1-29.5) and patients with acute kidney injury (24.3%; 19.3-30.7). Conclusions: This novel review provides a comprehensive and valuable resource on the prevalence and incidence of hyperkalaemia to better inform clinicians, healthcare providers and health policy makers on the burden of hyperkalaemia across different healthcare settings, patient populations and continents.

Clinical outcomes associated with the emergency treatment of hyperkalaemia with intravenous insulin-dextrose.

BACKGROUND: Hyperkalaemia occurs in up to 10% of hospital admissions but its treatment in the emergency setting is inconsistent. OBJECTIVES: To describe the emergency management of hyperkalaemia in adults with insulin-dextrose (IDex) and to explore clinical outcomes associated with IDex treatment. DESIGN AND SETTING: Cohort study using comprehensive electronic health records of all emergency admissions to a large university hospital in the United Kingdom between April 2015 and August 2018. PARTICIPANTS: Adult patients aged ≥16 years with at least one emergency admission and one blood potassium result during the study period. MAIN OUTCOMES AND MEASURES: Emergency hyperkalaemia treatment was evaluated including the requirement for re-treatment with IDex, episodes of glucose dysregulation, intensive care (ICU) admission and length of hospital stay. Associations with hyperkalaemia, adverse events and IDex treatment were explored by logistic regression. RESULTS: Amongst 211,993 patients attending the Emergency Department (ED) we identified 11,107 hyperkalaemic adult patients, of whom 1,284 were treated with IDex. Multiple doses were required in 542 patients (42.2%). Hypoglycaemia (plasma glucose < 4 mmol/L) occurred in 249 patients (19.4%) within 6 hours of IDex. Repeated doses were associated with an increased risk of hypoglycaemia (OR 2.94, 95% CI 2.20 to 3.93) compared to patients receiving a single dose, which, after adjustment was also associated with an increased risk of death (OR 1.56, 95% CI 1.16 to 2.09) during the study period. Patients who received multiple doses of IDex (OR 2.2, 95% CI 1.6-3.1) and those who received a dose of insulin above the guideline recommended limit (OR 5.6 3.1-10.3) were more likely to be admitted to ICU following IDex than those who received a single dose or the guideline recommended dose of insulin. CONCLUSIONS AND RELEVANCE: This study provides novel insight into the emergency management of hyperkalaemia in a large population, demonstrates the high risk of hypoglycaemia and highlights the urgent need for an improved, evidence-based approach to the emergency management of hyperkalaemia.

Adverse clinical outcomes associated with RAAS inhibitor discontinuation: analysis of over 400 000 patients from the UK Clinical Practice Research Datalink (CPRD).

BACKGROUND: Users of guideline-recommended renin-angiotensin-aldosterone system (RAAS) inhibitors may experience disruptions to their treatment, e.g. due to hyperkalaemia, hypotension or acute kidney injury. The risks associated with treatment disruption have not been comprehensively assessed; therefore, we evaluated the risk of adverse clinical outcomes in RAAS inhibitor users experiencing treatment disruptions in a large population-wide database. METHODS: This exploratory, retrospective analysis utilized data from the UK's Clinical Practice Research Datalink, linked to Hospital Episodes Statistics and the Office for National Statistics databases. Adults (≥18 years) with first RAAS inhibitor use (defined as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) between 1 January 2009 and 31 December 2014 were eligible for inclusion. Time to the first occurrence of adverse clinical outcomes [all-cause mortality, all-cause hospitalization, cardiac arrhythmia, heart failure hospitalization, cardiac arrest, advancement in chronic kidney disease (CKD) stage and acute kidney injury] was compared between RAAS inhibitor users with and without interruptions or cessations to treatment during follow-up. Associations between baseline characteristics and adverse clinical outcomes were also assessed. RESULTS: Among 434 027 RAAS inhibitor users, the risk of the first occurrence of all clinical outcomes, except advancement in CKD stage, was 8-75% lower in patients without interruptions or cessations versus patients with interruptions/cessations. Baseline characteristics independently associated with increased risk of clinical outcomes included increasing age, smoking, CKD, diabetes and heart failure. CONCLUSIONS: These findings highlight the need for effective management of factors associated with RAAS inhibitor interruptions or cessations in patients for whom guideline-recommended RAAS inhibitor treatment is indicated.