How to tackle therapeutic inertia in heart failure with reduced ejection fraction. A scientific statement of the Heart Failure Association of the ESC.

Guideline-directed medical therapy (GDMT) in patients with heart failure and reduced ejection fraction (HFrEF) reduces morbidity and mortality, but its implementation is often poor in daily clinical practice. Barriers to implementation include clinical and organizational factors that might contribute to clinical inertia, i.e. avoidance/delay of recommended treatment initiation/optimization. The spectrum of strategies that might be applied to foster GDMT implementation is wide, and involves the organizational set-up of heart failure care pathways, tailored drug initiation/optimization strategies increasing the chance of successful implementation, digital tools/telehealth interventions, educational activities and strategies targeting patient/physician awareness, and use of quality registries. This scientific statement by the Heart Failure Association of the ESC provides an overview of the current state of GDMT implementation in HFrEF, clinical and organizational barriers to implementation, and aims at suggesting a comprehensive framework on how to overcome clinical inertia and ultimately improve implementation of GDMT in HFrEF based on up-to-date evidence.

Dietary sodium and fluid intake in heart failure. A clinical consensus statement of the Heart Failure Association of the ESC.

Sodium and fluid restriction has traditionally been advocated in patients with heart failure (HF) due to their sodium and water avid state. However, most evidence regarding the altered sodium handling, fluid homeostasis and congestion-related signs and symptoms in patients with HF originates from untreated patient cohorts and physiological investigations. Recent data challenge the beneficial role of dietary sodium and fluid restriction in HF. Consequently, the European Society of Cardiology HF guidelines have gradually downgraded these recommendations over time, now advising for the limitation of salt intake to no more than 5 g/day in patients with HF, while contemplating fluid restriction of 1.5-2 L/day only in selected patients. Therefore, the objective of this clinical consensus statement is to provide advice on fluid and sodium intake in patients with acute and chronic HF, based on contemporary evidence and expert opinion.

Impact of Colorectal Nurse Specialist supervised parental administration of rectal washouts on Hirschsprung's disease outcomes: a retrospective review.

PURPOSE: To highlight the utility of Colorectal Nurse Specialist (CNS) supervised parental administration of rectal washouts in the management of Hirschsprung's disease (HD). METHODS: Retrospective case note review of HD patients treated at a tertiary children's hospital in United Kingdom from January 2011 to December 2022. Data collected included demographics, complications, enterocolitis, obstructive symptoms and stomas. Primary pull-through (PT) is done 8-12 weeks after birth. Parental expertise in performing rectal washouts at home is ensured by our CNS team before and after PT. RESULTS: PT was completed in 69 of 74 HD patients. Rectal washouts were attempted on 63 patients before PT. Failure of rectal washout efficacy necessitated a stoma in four patients (6.4%). Of the 65 patients who had PT and stoma closed, three (4.5%) required a further stoma over a mean follow-up period of 57 months (Range 7-144 months). Two of these had intractable diarrhoea due to Total Colonic Aganglionosis (TCA). One patient (1.5%) had unmanageable obstructive symptoms requiring re-diversion. Hirschsprung-associated enterocolitis (HAEC) requiring hospital admission occurred in 14 patients (21%). CONCLUSION: Our stoma rates are lower compared to recent UK data. This could potentially be due to emphasis on parental ability to perform effective rectal washouts at home under CNS supervision.

A Comparison of Sodium-Glucose Co-Transporter 2 Inhibitor Kidney Outcome Trial Participants with a Real-World Chronic Kidney Disease Primary Care Population.

BACKGROUND/HYPOTHESIS: Observational studies suggest sodium-glucose co-transporter-2 (SGLT2) inhibitor kidney outcome trials are not representative of the broader population of people with chronic kidney disease (CKD). However, there are limited data on the generalisability to those without co-existing type 2 diabetes (T2D), and the representativeness of the EMPA-KIDNEY trial has not been adequately explored. We hypothesised that SGLT2 inhibitor kidney outcome trials are more representative of people with co-existing T2D than those without, and that EMPA-KIDNEY is more representative than previous trials. METHODS: A cross-sectional analysis of adults with CKD in English primary care was conducted using the Oxford-Royal College of General Practitioners Clinical Information Digital Hub. The proportions that met the eligibility criteria of SGLT2 inhibitor kidney outcome trials were determined, and their characteristics described. Logistic regression analyses were performed to identify factors associated with trial eligibility. RESULTS: Of 6,670,829 adults, 516,491 (7.7%) with CKD were identified. In the real-world CKD population, 0.9%, 2.2%, and 8.0% met the CREDENCE, DAPA-CKD, and EMPA-KIDNEY eligibility criteria, respectively. All trials were more representative of people with co-existing T2D than those without T2D. Trial participants were 9-14 years younger than the real-world CKD population, and had more advanced CKD, including higher levels of albuminuria. A higher proportion of the CREDENCE (100%), DAPA-CKD (67.6%) and EMPA-KIDNEY (44.5%) trial participants had T2D compared to the real-world CKD population (32.8%). Renin-angiotensin system inhibitors were prescribed in almost all trial participants, compared to less than half of the real-world CKD population. Females were under-represented and less likely to be eligible for the trials. CONCLUSION: SGLT2 inhibitor kidney outcome trials represent a sub-group of people with CKD at high risk of adverse kidney events. Out study highlights the importance of complementing trials with real-world studies, exploring the effectiveness of SGLT2 inhibitors in the broader population of people with CKD.

The dynamics and outcomes of AKI progression during the COVID-19 pandemic.

PURPOSE: Acute kidney injury (AKI) associated with COVID-19 is associated with poor prognosis. This study assessed the hitherto uninvestigated impact of COVID-19 on the progression and clinical outcomes of patients with AKI. METHODS: Data from 576 patients with AKI admitted between 13/3/20 and 13/5/20 were studied. Increasingly complex analyses, from logistic regressions to competing-risk and multi-state models, have revealed insights into AKI progression dynamics associated with PCR-confirmed COVID-19 acquisition and death. Meta-analyses of case fatality ratios among patients with AKI were also conducted. RESULTS: The overall case-fatality ratio was 0.33 [95% CI (0.20-0.36)]; higher in COVID-19 positive (COVID+) patients 0.52 [95% CI (0.46-0.58)] than in their negative (COVID-) counterparts 0.16 [95% CI (0.12-0.20)]. In AKI Stage-3 patients, that was 0.71 [95% CI (0.64-0.79)] among COVID+ patients with 45% dead within 14 days and 0.35 [95% CI (0.25-0.44)] in the COVID- group and 28% died within 14 days. Among patients diagnosed with AKI Stage-1 within 24 h, the probability of progression to AKI Stage-3 on day 7 post admission was 0.22 [95% CI (0.17-0.27)] among COVID+ patients, and 0.06 [95% CI (0.03, 0.09)] among those who tested negative. The probability of discharge by day 7 was 0.71 [95% CI (0.66, 0.75)] in COVID- patients, and 0.27 [95% CI (0.21, 0.32)] in COVID+ patients. By day 14, in AKI Stage-3 COVID+ patients, that was 0.35 [95% CI (0.25, 0.44)] with little change by day 10, that is, 0.38 [95% CI (0.29, 0.47)]. CONCLUSION: These results are consistent with either a rapid progression in severity, prolonged hospital care, or high case fatality ratio among AKI Stage-3 patients, significantly exacerbated by COVID-19 infection.

Investigating the relationship between FRailty And Quality of LIfe in patients with heart faiLure and CKD (FRAIL study).

AIMS: Patients with chronic kidney disease (CKD) or heart failure (HF) are disproportionally affected by frailty, an independent predictor of morbidity. The prevalence of frailty and its impact on quality of life (QoL) in a unique population of patients with both CKD and HF (CKD-HF) is unclear. The aim of this study was to investigate the association between frailty and QoL in patients with CKD-HF. METHODS AND RESULTS: Patients were identified from a tertiary care cardiorenal clinic. Eligible patients had CKD-HF with a stable estimated glomerular filtration rate of <60 mL/min/1.732. Data were collected from each participant at one point in time using surveys delivered by study personnel between 14 July 2022 and 31 March 2023. Frailty was defined as Modified Frailty Phenotype (MFP) score ≥3. The Medical Outcomes Study 36-item Short Form Health Survey (SF-36) was used to assess QoL. Demographic data were retrospectively collected from electronic patient records. Demographics and QoL were compared between frail and non-frail cohorts using Pearson's R and Student's t-test (two-tailed, alpha-priori = 0.05). One hundred five participants consented, and 103 completed the questionnaires in full. Amongst the 103 participants, 49.5% (n = 51) were frail. Frailty was related to sex (P = 0.021) and medication count (P = 0.007), however not to other clinical measures, including estimated glomerular filtration rate (P = 0.437) and ejection fraction (P = 0.911). Frail patients reported poorer QoL across physical functioning (P < 0.001), general health (P < 0.001), bodily pain (P = 0.004), social functioning (P < 0.001), and energy levels (P < 0.001), however not emotional wellbeing (P = 0.058); 51.5% cited 'better quality of life' as their healthcare priority, over longer survival (23.3%) or avoiding hospital admissions (22.3%). This was consistent across frail and non-frail groups. CONCLUSIONS: A large proportion of CKD-HF patients are frail, regardless of disease severity, and more susceptible to significantly poorer QoL across physical and social domains. Improving QoL is the priority of patients across both frail and non-frail cohorts, further emphasizing the need for prompt recognition of frailty as well as possible intervention and prevention.

Asymptotic Freedom at the Berezinskii-Kosterlitz-Thouless Transition without Fine-Tuning Using a Qubit Regularization.

We propose a two-dimensional hard-core loop-gas model as a way to regularize the asymptotically free massive continuum quantum field theory that emerges at the Berezinskii-Kosterlitz-Thouless transition. Without fine-tuning, our model can reproduce the universal step-scaling function of the classical lattice XY model in the massive phase as we approach the phase transition. This is achieved by lowering the fugacity of Fock-vacuum sites in the loop-gas configuration space to zero in the thermodynamic limit. Some of the universal quantities at the Berezinskii-Kosterlitz-Thouless transition show smaller finite size effects in our model as compared to the traditional XY model. Our model is a prime example of qubit regularization of an asymptotically free massive quantum field theory in Euclidean space-time and helps understand how asymptotic freedom can arise as a relevant perturbation at a decoupled fixed point without fine-tuning.

Implementation of chronic kidney disease guidelines for sodium-glucose co-transporter-2 inhibitor use in primary care in the UK: a cross-sectional study.

Background: The cardiovascular and kidney benefits of sodium-glucose co-transporter-2 (SGLT2) inhibitors in people with chronic kidney disease (CKD) are well established. The implementation of updated SGLT2 inhibitor guidelines and prescribing in the real-world CKD population remains largely unknown. Methods: A cross-sectional study of adults with CKD registered with UK primary care practices in the Oxford-Royal College of General Practitioners Research and Surveillance Centre network on the 31st December 2022 was undertaken. Pseudonymised data from electronic health records held securely within the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID) were extracted. An update to a previously described ontological approach was used to identify the study population, using a combination of Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) indicating a diagnosis of CKD and laboratory confirmed CKD based on Kidney Disease: Improving Global Outcomes (KDIGO) diagnostic criteria. We examined the extent to which SGLT2 inhibitor guidelines apply to and are then implemented in adults with CKD. A logistic regression model was used to identify factors associated with SGLT2 inhibitor prescribing, reported as odds ratios (ORs) with 95% confidence intervals (CI). The four guidelines under investigation were the United Kingdom Kidney Association (UKKA) Clinical Practice Guideline SGLT2 Inhibition in Adults with Kidney Disease (October 2021), American Diabetes Association (ADA) and KDIGO Consensus Report on Diabetes Management in CKD (October 2022), National Institute for Health and Care Excellence (NICE) Guideline Type 2 Diabetes in Adults: Management (June 2022), and NICE Technology Appraisal Dapagliflozin for Treating CKD (March 2022). Findings: Of 6,670,829 adults, we identified 516,491 (7.7%) with CKD, including 32.8% (n = 169,443) who had co-existing type 2 diabetes (T2D). 26.8% (n = 138,183) of the overall CKD population had a guideline directed indication for SGLT2 inhibitor treatment. A higher proportion of people with CKD and co-existing T2D were indicated for treatment, compared to those without T2D (62.8% [n = 106,468] vs. 9.1% [n = 31,715]). SGLT2 inhibitors were prescribed to 17.0% (n = 23,466) of those with an indication for treatment, and prescriptions were predominantly in those with co-existing T2D; 22.0% (n = 23,464) in those with T2D, and <0.1% (n = 2) in those without T2D. In adjusted multivariable analysis of people with CKD and T2D, females (OR 0.69, 95% CI 0.67-0.72, p <0.0001), individuals of Black ethnicity (OR 0.84, 95% CI 0.77-0.91, p <0.0001) and those of lower socio-economic status (OR 0.72, 95% CI 0.68-0.76, p <0.0001) were less likely to be prescribed an SGLT2 inhibitor. Those with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 had a lower likelihood of receiving an SGLT2 inhibitor, compared to those with an eGFR ≥60 mL/min/1.73 m2 (eGFR 45-60 mL/min/1.73 m2 OR 0.65, 95% CI 0.62-0.68, p <0.0001, eGFR 30-45 mL/min/1.73 m2 OR 0.73, 95% CI 0.69-0.78, p <0.0001, eGFR 15-30 mL/min/1.73 m2 OR 0.52, 95% CI 0.46-0.60, p <0.0001, eGFR <15 mL/min/1.73 m2 OR 0.03, 95% CI 0.00-0.23, p = 0.0037, respectively). Those with albuminuria (urine albumin-to-creatinine ratio 3-30 mg/mmol) were less likely to be prescribed an SGLT2 inhibitor, compared to those without albuminuria (OR 0.78, 95% CI 0.75-0.82, p <0.0001). Interpretation: SGLT2 inhibitor guidelines in CKD have not yet been successfully implemented into clinical practice, most notably in those without co-existing T2D. Individuals at higher risk of adverse outcomes are paradoxically less likely to receive SGLT2 inhibitor treatment. The timeframe between the publication of guidelines and data extraction may have been too short to observe changes in clinical practice. Enhanced efforts to embed SGLT2 inhibitors equitably into routine care for people with CKD are urgently needed, particularly in those at highest risk of adverse outcomes and in the absence of T2D. Funding: None.

Small-Group Teaching: Should It Be Recorded?

Background: Recording large-group lectures is commonplace in higher education, allowing students to access content asynchronously and remotely. With the move towards online learning during the COVID-19 pandemic, recording of small-group teaching sessions has also become increasingly common; however, the educational value of this practice is unknown. Methods: All medical students rotating through the Acute Medicine Department of a large teaching hospital were invited to enrol in the study. Consenting students were recorded for the second half of an online case-based learning (CBL) session. The recording was available for 6 months; viewing patterns were analysed. Students were sent a questionnaire after the session, asking them to reflect on the recorded and unrecorded halves of the session. Findings: Thirty-three students underwent recording in 12 separate groups; 31 students (94%) completed the questionnaire. All 31 respondents (100%) described the session as "useful" or "very useful". Twenty-four respondents (77%) recommended continuing to record small-group sessions and 17 (55%) reported being "likely" or "very likely" to watch the recording. Six respondents (19%) reported a negative impact of being recorded. During 6 months of follow-up, no students returned to view the recording for more than 1 minute. Conclusion: Despite positive feedback for the session and high student demand for ongoing recording, no students viewed the recording for any significant duration. One-fifth of students reported a negative impact of being recorded. The findings from this study do not support routine recording of small-group CBL sessions, even where demand for this may exist. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01837-5.

Gaps in Modern Heart Failure and Chronic Kidney Disease Research.

Heart failure and chronic kidney disease are common conditions and often coexist. Modern clinical trials are not entirely representative of heart failure patients in the community with respect to age and sex. Despite this, another group of heart failure patients, those with advanced chronic kidney disease, are even less represented in modern clinical trials. This review summarises the evidence for heart failure therapies across age, sex and severity of chronic kidney disease, and outlines the need for further research in these populations.

A Randomized Trial of Intravenous Iron Supplementation and Exercise on Exercise Capacity in Iron-Deficient Nonanemic Patients With CKD.

Introduction: Patients with chronic kidney disease (CKD) are often iron deficient, even when not anemic. This trial evaluated whether iron supplementation enhances exercise capacity of nonanemic patients with CKD who have iron-deficiency. Methods: Prospective, multicenter double-blind randomized controlled trial of nondialysis patients with CKD and iron-deficiency but without anemia (Hemoglobin [Hb] >110 g/l). Patients were assigned 1:1 to intravenous (IV) iron therapy, or placebo. An 8-week exercise program commenced at week 4. The primary outcome was the mean between-group difference in 6-minute walk test (6MWT) at 4 weeks. Secondary outcomes included 6MWT at 12 weeks, transferrin saturation (TSAT), serum ferritin (SF), Hb, renal function, muscle strength, functional capacity, quality of life, and adverse events at baseline, 4 weeks, and at 12 weeks. Mean between-group differences were analyzed using analysis of covariance models. Results: Among 75 randomized patients, mean (SD) age for iron therapy (n = 37) versus placebo (n = 38) was 54 (16) versus 61 (12) years; estimated glomerular filtration rate (eGFR) (34 [12] vs. 35 [11] ml/min per 1.73 m2], TSAT (23 [12] vs. 21 [6])%; SF (57 [64] vs. 62 [33]) µg/l; Hb (122.4 [9.2] vs. 127 [13.2] g/l); 6MWT (384 [95] vs. 469 [142] meters) at baseline, respectively. No significant mean between-group difference was observed in 6MWT distance at 4 weeks. There were significant increases in SF and TSAT at 4 and 12 weeks (P < 0.02), and Hb at 12 weeks (P = 0.009). There were no between-group differences in other secondary outcomes and no adverse events attributable to iron therapy. Conclusion: This trial did not demonstrate beneficial effects of IV iron therapy on exercise capacity at 4 weeks. A larger study is needed to confirm if IV iron is beneficial in nondialysis patients with CKD who are iron-deficient.

Cardiac Troponin, Kidney Function, Heart Failure and Mortality After Myocardial Infarction in Patients With and Without Kidney Impairment.

Cardiac troponins (cTn) are routinely measured for the diagnosis and prognosis of myocardial infarction (MI). The relation between troponin levels, estimated glomerular filtration rate (eGFR), postinfarction heart failure (HF), and mortality is unclear in patients with kidney impairment. This is a retrospective, cross-sectional study of patients presenting to the Emergency Department at a single tertiary center. Participants presenting with confirmed type I MI from January 1, 2019, to December 31, 2021, were analyzed from the Myocardial Ischemia National Audit Project database. Main outcomes were acute HF, measured using Killip class, and inpatient mortality. Peak cardiac troponin T (cTnT) level was a secondary outcome. Data on 2,815 patients (67±14 years, 28% female) were analyzed. Ordinal logistic regression analysis was used to test for predictors of increasing Killip class. Binary logistic regression was used to test for predictors of inpatient mortality. Analysis of a sub-sample matched for age and diabetes mellitus status showed increased mortality in patients with eGFR <60 ml/min/1.73 m2 (12.2% vs 4.4%, p <0.001). Multivariate predictors of acute HF included log-transformed peak cTnT, eGFR, body mass index (BMI), and diabetes mellitus status. Multivariate predictors of inpatient mortality included log-transformed peak cTnT, eGFR, age, BMI, and Killip class 3/4. On multivariate analysis, eGFR, ST-elevation MI diagnosis, BMI, male gender, diabetes mellitus status, and hypertension were all predictive of peak cTnT after MI. In conclusion, peak cTnT level and eGFR at presentation after MI are independent predictors of acute HF severity and death in patients with and without kidney impairment.

Practical approaches to building up a cardiorenal clinic.

The population with concomitant heart and kidney disease (often termed 'cardiorenal' disease) is expected to grow, significantly impacting public health and healthcare utilization. Moreover, the cardiorenal nexus encompasses a bidirectional relationship that worsens prognosis and may complicate pharmacological management in often elderly and frail patients. Therefore, a more cohesive multidisciplinary team approach aiming to provide holistic, coordinated and specialized care would be a positive shift towards improving patient outcomes and optimizing healthcare resources. This article aims to define the organizational aspects and key elements for setting up a multidisciplinary cardiorenal clinical program as a potential healthcare model adapted to the particular characteristics of patients with cardiorenal disease.

Sodium-glucose cotransporter-2 inhibitors and kidney outcomes in real-world type 2 diabetes populations: A systematic review and meta-analysis of observational studies.

AIM: To conduct a systematic review of observational studies to explore the real-world kidney benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors in a large and diverse population of adults with type 2 diabetes (T2D). MATERIALS AND METHODS: We searched MEDLINE, EMBASE and Web of Science for observational studies that investigated kidney disease progression in adults with T2D treated with SGLT2 inhibitors compared to other glucose-lowering therapies. Studies published from database inception to July 2022 were independently reviewed by two authors and evaluated using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. A random-effects meta-analysis was performed on studies with comparable outcome data, reported as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: We identified 34 studies performed across 15 countries with a total population of 1 494 373 for inclusion. In the meta-analysis of 20 studies, SGLT2 inhibitors were associated with a 46% lower risk of kidney failure events compared with other glucose-lowering drugs (HR 0.54, 95% CI 0.47-0.63). This finding was consistent across multiple sensitivity analyses and was independent of baseline estimated glomerular filtration rate (eGFR) or albuminuria status. SGLT2 inhibitors were associated with a lower risk of kidney failure when compared with dipeptidyl peptidase-4 inhibitors and a combination of other glucose-lowering drug classes (HR 0.50, 95% CI 0.38-0.67 and HR 0.51, 95% CI 0.44-0.59, respectively). However, when compared to glucagon-like peptide 1 receptor agonists there was no statistically significant difference in the risk of kidney failure (HR 0.93, 95% CI 0.80-1.09). CONCLUSIONS: The reno-protective benefits of SGLT2 inhibitors apply to a broad population of adults with T2D treated in routine clinical practice, including those at lower risk of kidney events with normal eGFR and without albuminuria. These findings support the early use of SGLT2 inhibitors in T2D for preservation of kidney health.

Weak Universality Induced by Q=±2e Charges at the Deconfinement Transition of a (2+1)-Dimensional U(1) Lattice Gauge Theory.

Matter-free lattice gauge theories (LGTs) provide an ideal setting to understand confinement to deconfinement transitions at finite temperatures, which is typically due to the spontaneous breakdown (at large temperatures) of the center symmetry associated with the gauge group. Close to the transition, the relevant degrees of freedom (Polyakov loop) transform under these center symmetries, and the effective theory depends on only the Polyakov loop and its fluctuations. As shown first by Svetitsky and Yaffe, and subsequently verified numerically, for the U(1) LGT in (2+1) dimensions, the transition is in the 2D XY universality class, while for the Z_{2} LGT, it is in the 2D Ising universality class. We extend this classic scenario by adding higher charged matter fields and show that the critical exponents γ and ν can change continuously as a coupling is varied, while their ratio is fixed to the 2D Ising value. While such weak universality is well known for spin models, we demonstrate this for LGTs for the first time. Using an efficient cluster algorithm, we show that the finite temperature phase transition of the U(1) quantum link LGT in the spin S=1/2 representation is in the 2D XY universality class, as expected. On the addition of Q=±2e charges distributed thermally, we demonstrate the occurrence of weak universality.

Hyperkalemia in Chronic Kidney Disease: Links, Risks and Management.

Hyperkalemia is a common clinical problem with potentially fatal consequences. The prevalence of hyperkalemia is increasing, partially due to wide-scale utilization of prognostically beneficial medications that inhibit the renin-angiotensin-aldosterone-system (RAASi). Chronic kidney disease (CKD) is one of the multitude of risk factors for and associations with hyperkalemia. Reductions in urinary potassium excretion that occur in CKD can lead to an inability to maintain potassium homeostasis. In CKD patients, there are a variety of strategies to tackle acute and chronic hyperkalemia, including protecting myocardium from arrhythmias, shifting potassium into cells, increasing potassium excretion from the body, addressing dietary intake and treating associated conditions, which may exacerbate problems such as metabolic acidosis. The evidence base is variable but has recently been supplemented with the discovery of novel oral potassium binders, which have shown promise and efficacy in studies. Their use is likely to become widespread and offers another tool to the clinician treating hyperkalemia. Our review article provides an overview of hyperkalemia in CKD patients, including an exploration of relevant guidelines and nuances around management.

Management of Heart Failure in Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) is increasingly prevalent in patients with heart failure (HF) and HF is one of the leading causes of hospitalisation, morbidity and mortality in patients with impaired renal function. Currently, there is strong evidence to support the symptomatic and prognostic benefits of ß-blockers, renin-angiotensin-aldosterone inhibitors (RAASis), angiotensin receptor-neprilysin inhibitors (ARNIs) and mineralocorticoid receptor antagonists (MRA) in patients with HF and CKD stages 1-3. However, ARNIs, RAASis and MRAs are often suboptimally prescribed for patients with CKD owing to concerns about hyperkalaemia and worsening renal function. There is growing evidence for the use of sodium-glucose co-transporter 2 inhibitors and IV iron therapy in the management of HF in patients with CKD. However, few studies have included patients with CKD stages 4-5 and patients receiving dialysis, limiting the assessment of the safety and efficacy of these therapies in advanced CKD. Interdisciplinary input from HF and renal specialists is required to provide integrated care for the growing number of patients with HF and CKD.

The effect of intravenous iron supplementation on exercise capacity in iron-deficient but not anaemic patients with chronic kidney disease: study design and baseline data for a multicentre prospective double-blind randomised controlled trial.

BACKGROUND: Many people living with chronic kidney disease (CKD) are iron deficient, even though they may not be anaemic. The Iron and Muscle study aims to evaluate whether iron supplementation reduces symptoms of fatigue, improves muscle metabolism, and leads to enhanced exercise capacity and physical function. We report here the trial design and baseline characteristics. METHODS: This is a prospective, double-blind multicentre randomised controlled trial (RCT) including 75 non-dialysis stage 3-4 CKD patients with iron deficiency but without anaemia. Patients were randomly (1:1) assigned to either: i) intravenous iron therapy, or ii) placebo, with concurrent recruitment of eight CKD non-iron deficient participants and six healthy volunteers. The primary outcome of the study is the six-minute walk test (6MWT) distance between baseline and four-weeks. An additional exercise training programme for patients in both groups was initiated and completed between 4 and 12 weeks, to determine the effect of iron repletion compared to placebo treatment in the context of patients undertaking an exercise programme. Additional secondary outcomes include fatigue, physical function, muscle strength, muscle metabolism, quality of life, resting blood pressure, clinical chemistry, safety and harms associated with the iron therapy intervention and the exercise training intervention, and hospitalisations. All outcomes were conducted at baseline, 4, and 12 weeks, with a nested qualitative study, to investigate the experience of living with iron deficiency and intervention acceptability. The cohort have been recruited and baseline assessments undertaken. RESULTS: Seventy-five individuals were recruited. 44% of the randomised cohort were male, the mean (SD) age was 58 (14) years, and 56% were White. Body mass index was 31 (7) kg/m2; serum ferritin was 59 (45) µg/L, transferrin saturation was 22 (10) %, and haemoglobin was 125 (12) g/L at randomisation for the whole group. Estimated glomerular filtration rate was 35 (12) mL/min/1.73 m2 and the baseline 6MWT distance was 429 (174) m. CONCLUSION: The results from this study will address a substantial knowledge gap in the effects of intravenous iron therapy, and offer potential clinical treatment options, to improve exercise capacity, physical function, fatigue, and muscle metabolism, for non-dialysis patients with CKD who are iron-deficient but not anaemic. It will also offer insight into the potential novel effects of an 8-week exercise training programme. TRIAL REGISTRATION: EudraCT: 2018-000,144-25 Registered 28/01/2019.

Catheter Ablation for Atrial Fibrillation in Patients with Chronic Kidney Disease and on Dialysis: A Meta-Analysis and Review.

BACKGROUND: Atrial fibrillation (AF) is common in chronic kidney disease (CKD) patients and is difficult to treat with anti-arrhythmics and anticoagulants due to abnormal metabolism and increased side effects. Catheter ablation, if successful, may be a safer alternative. This review aimed to analyse the effect of CKD or haemodialysis (HD) on recurrence of AF after catheter ablation. METHODS: MEDLINE, Embase, and PubMed databases were searched until December 2020. Two authors abstracted the data independently. Relative risks were derived using random-effects meta-analysis. RESULTS: Of the initially identified 782 studies, 6 and 4 observational studies investigating CKD and HD patients, respectively reported AF recurrence rates. During a mean (SD) follow-up of 25.5 (9.8) months, CKD patients demonstrated a higher risk of AF recurrence compared to patients without CKD (RR 2.34, 95% CI: 1.36-4.02, p < 0.01). The heterogenicity test highlighted significant differences between individual studies (I2 = 91.0%, 95% CI: 82.2-95.6%). In a mean (SD) follow-up of 32.6 (26.8) months, HD patients may be at a higher risk of AF recurrence compared to healthy non-dialysis AF patients (RR 1.50, 95% CI: 0.84-2.67, p = 0.17). Heterogeneity analysis showed the studies were heterogeneous (I2 = 90.1%, 95% CI: 77.5-95.6%, p < 0.01). CONCLUSION: Our meta-analysis suggests patients with CKD and on HD are more likely to have AF recurrences compared to AF patients who do not have CKD. However, more robust evidence from randomized controlled trials comparing catheter ablation to pharmaceutical rhythm therapy is urgently needed to guide therapy in this difficult to treat population.

Severity of COVID-19 after Vaccination among Hemodialysis Patients: An Observational Cohort Study.

BACKGROUND AND OBJECTIVES: Patients receiving hemodialysis are at high risk from coronavirus disease 2019 (COVID-19) and demonstrate impaired immune responses to vaccines. There have been several descriptions of their immunologic responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, but few studies have described the clinical efficacy of vaccination in patients on hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a multicenter observational study of the London hemodialysis population undergoing surveillance PCR testing during the period of vaccine rollout with BNT162b2 and AZD1222, all of those positive for SARS-CoV-2 were identified. Clinical outcomes were analyzed according to predictor variables, including vaccination status, using a mixed effects logistic regression model. Risk of infection was analyzed in a subgroup of the base population using a Cox proportional hazards model with vaccination status as a time-varying covariate. RESULTS: SARS-CoV-2 infection was identified in 1323 patients of different ethnicities (Asian/other, 30%; Black, 38%; and White, 32%), including 1047 (79%) unvaccinated, 86 (7%) after first-dose vaccination, and 190 (14%) after second-dose vaccination. The majority of patients had a mild course; however, 515 (39%) were hospitalized, and 172 (13%) died. Older age, diabetes, and immune suppression were associated with greater illness severity. In regression models adjusted for age, comorbidity, and time period, prior two-dose vaccination was associated with a 75% (95% confidence interval, 56 to 86) lower risk of admission and 88% (95% confidence interval, 70 to 95) fewer deaths compared with unvaccinated patients. No loss of protection was seen in patients over 65 years or with increasing time since vaccination, and no difference was seen between vaccine types. CONCLUSIONS: These data demonstrate a substantially lower risk of severe COVID-19 after vaccination in patients on dialysis who become infected with SARS-CoV-2.