Artificial Intelligence for Real-Time Prediction of the Histology of Colorectal Polyps by General Endoscopists.

BACKGROUND: Real-time prediction of histologic features of small colorectal polyps may prevent resection and/or pathologic evaluation and therefore decrease colonoscopy costs. Previous studies showed that computer-aided diagnosis (CADx) was highly accurate, though it did not outperform expert endoscopists. OBJECTIVE: To assess the diagnostic performance of histologic predictions by general endoscopists before and after assistance from CADx in a real-life setting. DESIGN: Prospective, multicenter, single-group study. (ClinicalTrials.gov: NCT04437615). SETTING: 6 centers across the United States. PARTICIPANTS: 1252 consecutive patients undergoing colonoscopy and 49 general endoscopists with variable experience in real-time prediction of polyp histologic features. INTERVENTION: Real-time use of CADx during routine colonoscopy. MEASUREMENTS: The primary end points were the sensitivity and specificity of CADx-unassisted and CADx-assisted histologic predictions for adenomas measuring 5 mm or less. For clinical purposes, additional estimates according to location and confidence level were provided. RESULTS: The CADx device made a diagnosis for 2695 polyps measuring 5 mm or less (96%) in 1252 patients. There was no difference in sensitivity between the unassisted and assisted groups (90.7% vs. 90.8%; P = 0.52). Specificity was higher in the CADx-assisted group (59.5% vs. 64.7%; P < 0.001). Among all 2695 polyps measuring 5 mm or less, 88.2% and 86.1% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be resected and discarded without pathologic evaluation. Among 743 rectosigmoid polyps measuring 5 mm or less, 49.5% and 47.9% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be left in situ without resection. LIMITATION: Decision making based on CADx might differ outside a clinical trial. CONCLUSION: CADx assistance did not result in increased sensitivity of optical diagnosis. Despite a slight increase, the specificity of CADx-assisted diagnosis remained suboptimal. PRIMARY FUNDING SOURCE: Olympus America Corporation served as the clinical study sponsor.

Atrial Fibrillation and Chronic Kidney Disease: Aetiology and Management.

Chronic kidney disease (CKD) and atrial fibrillation (AF) are associated with significant cardiovascular morbidity and mortality. Recent studies have highlighted an increased prevalence and incidence of AF in patients with CKD. This article aims to provide a comprehensive review of current management strategies and considerations of treating atrial fibrillation with concomitant CKD. Potential electrophysiological mechanisms between AF and CKD are explored. Current evidence and literature focusing on pharmacological rate and rhythm control along with procedural intervention is reviewed and presented. The management of AF and CKD together is complex, but particularly pertinent when considering the close cyclical relationship in the progression of both diseases.

Chronic illness as cultural disruption: The impact of chronic illness on religious and cultural practice.

The relationship between religion and health tends to be framed positively. Religion has been found to act as a coping mechanism and source of support in times of ill health. In this paper, we focus on the disruptive effect of chronic illness on religious practice and cultural engagement. Drawing on interviews with ethnic minority adults with end-stage kidney disease, who also identify as religious, we introduce the concept 'cultural disruption'. While religious practice and belief was found to provide strength and comfort we also found that chronic illness had a disruptive impact on religious and cultural practice that participants attempted to manage. To highlight the potential disruptive effect of chronic illness on religious faith and cultural engagement we identify three elements of cultural disruption-disruption to religious practice, disruption to sense of self and identity and disruption to wellbeing. We conclude by suggesting that understanding and accounting for the potential of cultural disruption when diagnosing, treating and supporting people with chronic illness offers an alternative entry point to the life-worlds of patients who identify as religious and the things that are important to them.

Defining myocardial infarction in trials of people receiving hemodialysis: consensus report from the SONG-HD MI Expert Working group.

Cardiovascular disease is the leading cause of death in patients receiving hemodialysis. Currently, there is no standardized definition of myocardial infarction (MI) for patients receiving hemodialysis. Through an international consensus process MI was established as the core CVD measure for this population in clinical trials. The Standardised Outcomes in Nephrology Group-Hemodialysis (SONG-HD) initiative convened a multidisciplinary, international working group to address the definition of MI in this population. On the basis of current evidence, the working group recommends using the Fourth Universal Definition of Myocardial Infarction with specific caveats with regard to the interpretation of "ischemic symptoms" and performing a baseline 12-lead electrocardiogram to facilitate interpretation of acute changes on subsequent tracings. The working group does not recommend obtaining baseline cardiac troponin values, though does recommend obtaining serial cardiac biomarkers in settings where ischemia is suspected. The application of an evidence-based uniform definition should increase the reliability and accuracy of trial results.

Systemic adiponectin levels in colorectal cancer and adenoma: a systematic review and meta-analysis.

BACKGROUND: Obesity is a well-established risk factor in the development of colorectal cancer; however, the mechanism mediating this relationship is not well understood. The adipokine, adiponectin, has an inverse relationship with obesity. Experimental studies have shown adiponectin to have dichotomous inflammatory and tumorigenic roles. Its role in the development of colorectal cancer, including the potential effect of its increase following bariatric surgery, is not yet clear. There are conflicting results from studies evaluating this relationship. This study sought to provide a systematic review and meta-analysis to examine the association between systemic adiponectin levels in patients with colorectal cancer and adenoma. METHODS: An electronic literature search was performed using PubMed, EMBASE, Web of Science as well as gray literature. Articles were screened for inclusion criteria and assessed for quality using the Newcastle-Ottawa Scale. Pooled mean differences were calculated using a random effects model. Subgroup and meta-regression analyses were performed to identify potential sources of heterogeneity. RESULTS: Thirty-two observational studies comparing systemic adiponectin in colorectal cancer vs healthy controls were included. Colorectal cancer cases had lower systemic adiponectin levels (overall pooled mean difference = -1.05 µg/ml [95% CI: -1.99; -0.12] p = 0.03); however, significant heterogeneity was present (I2 = 95% p < 0.01). Subgroup and meta- regression analyses results could not identify a source of the significant heterogeneity across the studies. CONCLUSIONS: Studies suggest a trend towards lower systemic adiponectin levels in colorectal cancer patients, but the heterogeneity observed showed current evidence is not sufficient to definitively draw any conclusions. These data, however, suggest rising adiponectin is unlikely to account for the reported observation of increased CRC following bariatric surgery. Further studies with prospective age, race, and BMI-matched cohorts, and standardized adiponectin measurements may provide a better understanding of this relationship.

Does cooled dialysate still have a role in reducing intradialytic stress? Implications of the MyTEMP trial.

PURPOSE OF REVIEW: There is an excess of cardiovascular morbidity and mortality in the maintenance haemodialysis population. Targeting traditional risk factors (e.g. hypercholesterolaemia) do not improve cardiovascular outcomes. Repeated myocardial stunning during haemodialysis is an important nontraditional risk, resulting in pathological cardiac remodelling and fibrosis. This review explores dialysate cooling as a management strategy to promote haemodynamic stability, reduce myocardial injury, and improve cardiovascular disease outcomes for individuals receiving maintenance haemodialysis. RECENT FINDINGS: Observational data and small interventional studies demonstrate dialysate cooling has the potential to reduce end-organ damage and provide cardioprotection, renal protection and neuroprotection compared with standard care. These data are limited by the small sample sizes, short follow-up times and lack of long-term patient important outcomes. The MyTEMP study, a multicentre pragmatic randomized controlled trial, demonstrated cooled dialysate (0.5°C below body temperature) vs. standard care did not improve cardiovascular outcomes for prevalent haemodialysis patients. SUMMARY: Dialysate cooling has been widely adopted into routine clinical practice; the MyTEMP study challenges the unit-level approach to implementing dialysate cooling. Due to methodological limitations, the absence of other important patient outcome measures, and lack of granularity of patient-level data, dialysate cooling should not be hastily removed from all dialysis care and warrants further research.

Physical activity and nutrition in chronic kidney disease.

PURPOSE OF REVIEW: Lifestyle intervention is considered a cornerstone in chronic kidney disease management and has been recommended in different international or regional clinical practice guidelines in chronic kidney disease. However, evidence was largely based on the general population. Here we summarized the latest evidence supporting lifestyle intervention in chronic kidney disease. RECENT FINDINGS: Both observational cohort studies as well as randomized controlled trials have demonstrated health benefits with more physical activity in chronic kidney disease. There are compelling observational data supporting different health and kidney benefits with a healthy dietary pattern rich in fruits and vegetables, whole grains, plant-based foods and low in salt, low in sugar, saturated fat, red meat and ultraprocessed foods, a plant-based diet or Mediterranean diet in chronic kidney disease population. Clinical and epidemiologic studies also showed that higher 24 h urine potassium excretion (as proxy of higher dietary potassium intake) may be associated with lower blood pressure, better kidney outcomes and lower mortality in chronic kidney disease population. Randomized controlled trials also suggested that salt substitutes improved blood pressure control, reduced all-cause death and cardiovascular event risk in the general population compared with regular salt. SUMMARY: Accumulating evidence supports the current recommendation of encouraging physical activity and promoting a healthy dietary pattern in chronic kidney disease patients. Whether potassium needs restriction in chronic kidney disease diet requires further review. The safety versus benefits of salt substitutes in patients with moderate and advanced chronic kidney disease warrants further investigation.

UK Kidney Association Clinical Practice Guideline: Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibition in Adults with Kidney Disease 2023 UPDATE.

Large placebo-controlled trials have demonstrated kidney and cardiovascular clinical benefits of SGLT-2 inhibitors. Data from the EMPA-KIDNEY and DELIVER trials and associated meta-analyses triggered an update to the UK Kidney Association Clinical Practice Guideline on Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibition in Adults with Kidney Disease. We provide a summary of the full guideline and highlight the rationale for recent updates. The use of SGLT-2 inhibitors in people with specific medical conditions, including type 1 diabetes, kidney transplants, and people admitted to hospital with heart failure is also considered, along with Recommendations for future research and Recommendations for implementation. A full "lay" summary of the guidelines is provided as an appendix to ensure that these guidelines are accessible and understandable to people who are not medical professionals.

Colorectal cancer screening: The role of MT-sDNA testing.

ABSTRACT: Because an estimated 10.5% of new colorectal cancer (CRC) cases occur in patients under age 50 years, the US Preventive Services Task Force in 2021 recommended CRC screening for adults ages 45 to 49 years. The prevalence of up-to-date CRC screening with any recommended test among patients age 45 years and older in the United States is only 59% in 2023, indicating that existing screening practices are ineffective. Screening options now include invasive and noninvasive measures. Multi-target stool DNA (MT-sDNA) testing is a simple, low-risk, noninvasive test that provides excellent sensitivity and specificity, is cost-effective, and may increase patient screening rates. CRC screening guideline recommendations and alternative screening methods may help improve patient outcomes and reduce morbidity and mortality. This article describes MT-sDNA testing, its effectiveness, recommended use, and potential expanding role as a screening option.

A multicenter feasibility randomized controlled trial to assess the impact of incremental versus conventional initiation of hemodialysis on residual kidney function.

Twice-weekly hemodialysis, as part of incremental initiation, has reported benefits including preservation of residual kidney function (RKF). To explore this, we initiated a randomized controlled feasibility trial examining 55 incident hemodialysis patients with urea clearance of 3 ml/min/1.73 m2 or more across four centers in the United Kingdom randomized to standard or incremental schedules for 12 months. Incremental hemodialysis involved twice-weekly sessions, upwardly adjusting hemodialysis dose as RKF was lost, maintaining total (Dialysis+Renal) Std Kt/V above 2. Standard hemodialysis was thrice weekly for 3.5-4 hours, minimum Dialysis Std Kt/V of 2. Primary outcomes were feasibility parameters and effect size of group differences in rate of loss of RKF at six months. Health care cost impact and patient-reported outcomes were explored. Around one-third of patients met eligibility criteria. Half agreed to randomization; 26 received standard hemodialysis and 29 incremental. At 12 months, 21 incremental patients remained in the study vs 12 in the standard arm with no group differences in the urea clearance slope. Ninety-two percent of incremental and 75% of standard arm patients had a urea clearance of 2 ml/min/1.73 m2 or more at six months. Serious adverse events were less frequent in incremental patients (Incidence Rate Ratio 0.47, confidence interval 0.27-0.81). Serum bicarbonate was significantly lower in incremental patients indicating supplementation may be required. There were three deaths in each arm. Blood pressure, extracellular fluid and patient-reported outcomes were similar. There was no signal of benefit of incremental hemodialysis in terms of protection of RKF or Quality of Life score. Median incremental hemodialysis costs were significantly lower compared to standard hemodialysis. Thus, incremental hemodialysis appears safe and cost-saving in incident patients with adequate RKF, justifying a definitive trial.

Novel approach to unpleasant symptom clusters surrounding pruritus in patients with chronic kidney disease and on dialysis therapy.

PURPOSE OF REVIEW: Chronic kidney disease-associated-pruritus (CKD-aP) is a common symptom in patients with end-stage kidney disease (ESKD) undergoing dialysis. CKD-aP typically occurs alongside other debilitating symptoms and may comprise so-called 'symptom clusters' which have synergistic effects that adversely impact patient health-related quality of life (HRQoL). Importantly, symptoms in a cluster may share a common biological mechanism. Here we review the clinical impact of CKD-aP and its association with other symptoms reported by dialysis patients. The clinical benefits of treating pruritus and its potential impact on other symptoms are also addressed. RECENT FINDINGS: Studies have shown CKD-aP significantly impairs HRQoL in patients with ESKD undergoing dialysis and is associated with adverse clinical outcomes, including increased risk of infections, hospitalizations, and mortality. Despite these negative effects, CKD-aP remains underrecognized and undertreated in clinical practice. CKD-aP is frequently associated with other symptoms, including disturbed sleep/poor sleep quality, anxiety, depression, and pain. Clinical studies of antipruritic therapies show that reduction of itch intensity may also alleviate other associated symptoms, such as poor sleep quality. SUMMARY: CKD-aP and its associated symptoms are inadequately managed in clinical practice. Greater understanding and awareness of CKD-aP and its surrounding symptom clusters in dialysis patients may improve their overall symptom management and HRQoL.

Prospective Multicenter Study of Early Antiviral Therapy in Liver and Kidney Transplant Recipients of HCV-Viremic Donors.

BACKGROUND AND AIMS: Organs from hepatitis C virus (HCV)-viremic donors have been used in HCV-uninfected recipients (D+/R-), but the optimal treatment approach has not been defined. We evaluated the kinetics of HCV infection following transplant in D+/R- kidney-transplant (KT) and liver-transplant (LT) recipients when a preemptive antiviral strategy was used. APPROACH AND RESULTS: Six US transplant programs prospectively treated D+/R- primary LT and KT recipients with sofosbuvir-velpastasvir for 12 weeks starting once viremia was confirmed following transplant and the patients were judged to be clinically stable, including estimated glomerular filtration rate >30 mL/min. Primary endpoints were sustained virologic response at 12 weeks following transplant and safety (assessed by proportion of treatment-related adverse and serious adverse events). Of the 24 patients transplanted (13 liver, of whom 2 had prior-treated HCV infection; 11 kidney), 23 became viremic after transplant. The median (interquartile range) time from transplant to start of antiviral therapy was 7.0 (6.0, 12.0) versus 16.5 (9.8, 24.5) days, and the median (interquartile range) HCV-RNA level 3 days after transplant was 6.5 (3.9, 7.1) versus 3.6 (2.9, 4.0) log10  IU/mL in LT versus KT recipients, respectively. By week 4 of treatment, 10 of 13 (77%) LT, but only 2 of 10 (20%) KT, had undetectable HCV RNA (P = 0.01). At the end of treatment, all LT recipients were HCV RNA-undetectable, whereas 3 (30%) of the kidney recipients still had detectable, but not quantifiable, viremia. All achieved sustained virologic response at 12 weeks following transplant (lower 95% confidence interval bound: 85%). Serious adverse events considered possibly related to treatment were antibody-mediated rejection, biliary sclerosis, cardiomyopathy, and graft-versus-host disease, with the latter associated with multiorgan failure, premature treatment discontinuation, and death. CONCLUSIONS: Despite differing kinetics of early HCV infection in liver versus non-liver recipients, a preemptive antiviral strategy is effective. Vigilance for adverse immunologic events is warranted.

Measuring quality of life in trials including patients on haemodialysis: methodological issues surrounding the use of the Kidney Disease Quality of Life Questionnaire.

BACKGROUND: Haemodialysis (HD) treatment causes a significant decrease in quality of life (QoL). When enrolled in a clinical trial, some patients are lost prior to follow-up because they die or they receive a kidney transplant. It is unclear how these patients are dealt with in the analysis of QoL data. There are questions surrounding the consistency of how QoL measures are used, reported and analysed. METHODS: A systematic search of electronic databases for trials measuring QoL in HD patients using any variation of the Kidney Disease Quality of Life (KDQoL) Questionnaire was conducted. The review was conducted in Covidence version 2. Quantitative analysis was conducted in Stata version 16. RESULTS: We included 61 trials in the review, of which 82% reported dropouts. The methods to account for missing data due to dropouts include imputation (7%) and complete case analysis (72%). Few trials (7%) conducted a sensitivity analysis to assess the impact of missing data on the study results. Single imputation techniques were used, but are only valid under strong assumptions regarding the type and pattern of missingness. There was inconsistency in the reporting of the KDQoL, with many articles (70%) amending the validated questionnaires or reporting only statistically significant results. CONCLUSIONS: Missing data are not dealt with according to the missing data mechanism, which may lead to biased results. Inconsistency in the use of patient-reported outcome measures raises questions about the validity of these trials. Methodological issues in nephrology trials could be a contributing factor to why there are limited effective interventions to improve QoL in this patient group. PROSPERO REGISTRATION: CRD42020223869.

Circulating endotoxin and inflammation: associations with fitness, physical activity and the effect of a 6-month programme of cycling exercise during haemodialysis.

BACKGROUND: Intradialytic cycling (IDC) may provide cardiovascular benefits to individuals receiving haemodialysis, but the exact mechanism behind these improvements remains unclear. The primary aim of this study was to investigate the effect of a 6-month programme of IDC on circulating endotoxin (secondary analysis from the CYCLE-HD trial). Secondary aims were to investigate changes in circulating cytokines [interleukin-6 (IL-6), IL-10, tumour necrosis factor-α, C-reactive protein (CRP) and the IL-6:IL-10 ratio] and their associations with physical activity, fitness and cardiovascular outcomes. METHODS: Participants were randomized to either a 6-month programme of IDC (thrice weekly, moderate intensity cycling at a rating of perceived exertion of 12-14) in addition to usual care (n = 46) or usual care only (control group; n = 46). Outcome measures were obtained at baseline and then again at 6 months. RESULTS: There was no significant (P = 0.137) difference in circulating endotoxin between groups at 6 months (IDC group: 0.34 ± 0.08 EU/mL; control group: 0.37 ± 0.07 EU/mL). There were no significant between-group differences in any circulating cytokine following the 6-month programme of IDC. Higher levels of physical activity and fitness were associated with lower levels of endotoxin, IL-6, CRP and IL-6:IL-10 ratio. CONCLUSIONS: Our data show no change in circulating endotoxin or cytokines following a 6-month programme of IDC. However, higher levels of physical activity outside of haemodialysis were associated with lower levels of inflammation.

Choledochoduodenostomy is associated with fewer post-transplant biliary complications compared to Roux-en-Y in primary sclerosing cholangitis patients.

BACKGROUND: For primary sclerosing cholangitis (PSC) patients undergoing liver transplantation (LT), a consensus regarding biliary reconstruction remains unresolved. Choledochoduodenostomy (CDD) represents an alternative to Roux-en-Y (RY) and duct-to-duct. We compared long-term post-transplant outcomes between CDD and RY. METHODS: This was a retrospective review of patients transplanted for PSC who received CDD or RY, with minimum 12-months follow-up. The primary outcome was need for biliary intervention, with either percutaneous transhepatic cholangiography (PTC) or endoscopic retrograde cholangiopancreatography (ERCP). Secondary outcomes included biliary stricture(s) and cholangitis admission(s). RESULTS: Ninety-three patients were transplanted between August 2004 and October 2019 (34 living donor [LDLT] and 59 deceased donor [DDLT]; 40 RY, 53 CDD). Need for either ERCP or PTC was similar (45.0% RY vs. 32.1% CDD, P = .203), though RY exhibited more anastomotic strictures (AS) (35.0% RY vs. 11.3% CDD, P = .006), which was also observed in LDLT subanalyses (50.0% LDLT/RY vs. 10.0% LDLT/CDD; P = .036). Cholangitis admissions were more frequent in RY versus CDD (37.5% vs. 15.1%, P = .013). CONCLUSIONS: CDD does not impart greater risk of biliary complications, and RY may have an incremental effect combined with LDLT status for predisposing to AS. CDD maintains standard endoscopic access without additional risk of biliary complications, thus should be considered when anatomically feasible.

Associations between physical activity levels and renal recovery following acute kidney injury stage 3: a feasibility study.

BACKGROUND: Acute kidney injury (AKI) can lead to chronic kidney disease, which results in poor long-term outcomes. There is plausibility that increased levels of physical activity may promote renal recovery post-AKI. This study aimed to investigate associations between physical activity levels and renal recovery following stage 3 AKI, and to assess the feasibility of measuring physical activity levels in this population. METHODS: Forty One hospitalised patients with AKI stage 3 were enrolled. Serum creatinine and estimated glomerular filtration rate (eGFR) were collected at 12 months prior to the development of AKI, during the hospital admission when the episode of AKI stage 3 occurred, and at 1-, 3- and 6-months post discharge. All participants completed the General Practice Activity Questionnaire (GPPAQ) to assess physical activity levels. A pedometer was also worn for 7 days immediately following discharge and at 6-months post discharge to ascertain an average daily step count. Feasibility outcomes including eligibility, recruitment and retention rates, and losses to follow up were also assessed. RESULTS: The average (± SD) baseline eGFR and median (IQR) serum creatinine was 71 ± 20 mL/min/1.73m2 and 85 (49) µmol/L respectively. A threefold increase in creatinine occurred during hospitalisation 436 (265) µmol/L. Greatest renal recovery occurred prior to discharge, with recovery continuing for a further three months. Inactive individuals (low GPPAQ scores) had consistently higher serum creatinine values compared to those who were active: 1 months 122 (111) µmol/L vs 70 (0) µmol/L, 6 months 112 (57) µmol/L vs 68 (0) µmol/L. Individuals with higher step counts also displayed better renal recovery 6-months post discharge (r = -0.600, p = 0.208). CONCLUSIONS: Higher levels of physical activity are associated with improved renal recovery after 6- months following an episode of stage 3 AKI. A future randomised controlled trial is feasible and would be required to confirm these initial findings.

Living with frailty and haemodialysis: a qualitative study.

BACKGROUND: Frailty is highly prevalent in people receiving haemodialysis (HD) and is associated with poor outcomes. Understanding the lived experiences of this group is essential to inform holistic care delivery. METHODS: Semi-structured interviews with N = 25 prevalent adults receiving HD from 3 HD units in the UK. Eligibility criteria included a Clinical Frailty Scale (CFS) score of 4-7 and a history of at least one fall in the last 6 months. Sampling began guided by maximum variation sampling to ensure diversity in frailty status; subsequently theoretical sampling enabled exploration of preliminary themes. Analysis was informed by constructivist grounded theory; later we drew upon the socioecological model. RESULTS: Participants had a mean age of 69 ± 10 years, 13 were female, and 13 were White British. 14 participants were vulnerable or mildly frail (CFS 4-5), and 11 moderately or severely frail (CFS 6-7). Participants characterised frailty as weight loss, weakness, exhaustion, pain and sleep disturbance arising from multiple long-term conditions. Participants' accounts revealed: the consequences of frailty (variable function and psychological ill-health at the individual level; increasing reliance upon family at the interpersonal level; burdensome health and social care interactions at the organisational level; reduced participation at the community level; challenges with financial support at the societal level); coping strategies (avoidance, vigilance, and resignation); and unmet needs (overprotection from family and healthcare professionals, transactional health and social care exchanges). CONCLUSIONS: The implementation of a holistic needs assessment, person-centred health and social care systems, greater family support and enhancing opportunities for community participation may all improve outcomes and experience. An approach which encompasses all these strategies, together with wider public health interventions, may have a greater sustained impact. TRIAL REGISTRATION: ISRCTN12840463 .

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.

Intradialytic cycling does not exacerbate microparticles or circulating markers of systemic inflammation in haemodialysis patients.

PURPOSE: Patients receiving haemodialysis (HD) display elevated circulating microparticle (MP) concentration, tissue factor (TF) expression and markers of systemic inflammation, though regular intradialytic cycling (IDC) may have a therapeutic effect. This study investigated the impact of regular, moderate-intensity IDC on circulating MPs and inflammatory markers in unit-based HD patients. METHODS: Patients were cluster-randomised to intervention (n = 20, age: 51.4 ± 18.1 years, body mass: 77.6 ± 18.3 kg, mean ± SD) or no-exercise control (n = 20, 56.8 ± 14.0 years, 80.5 ± 26.5 kg). Intervention participants completed 30 min of moderate intensity (rating of perceived exertion [RPE] of 12-14) IDC, thrice weekly for 6 months. Pre-dialysis venous blood samples were obtained at 0, 3 and 6 months. Circulating MP phenotypes, cytokines, chemokine and MP TF expression were quantified using flow cytometry and cytometric bead array assays. RESULTS: Despite high exercise compliance (82%), no IDC-dependent effects were observed for any MP, cytokine or chemokine measure (p ≥ 0.051, ηρ2 ≤ 0.399) other than TNF-α (p = 0.001, ηρ2 = 0.186), though no significance was revealed upon post hoc analysis. CONCLUSION: Six months of regular, moderate-intensity IDC had no effect on MPs, cytokines or chemokines. This suggests that the exercise did not exacerbate thrombotic or inflammatory status, though further functional assays are required to confirm this. TRIAL REGISTRATION: ISRCTN1129707, prospectively registered on 05/03/2015.

A Comparison of Dietary Intake Between Individuals Undergoing Maintenance Hemodialysis in the United Kingdom and China.

OBJECTIVE: Protein-energy wasting is highly prevalent in people with end-stage kidney disease receiving regular hemodialysis. Currently, it is unclear what the optimal nutritional recommendations are, which is further complicated by differences in dietary patterns between countries. The aim of the study was to understand and compare dietary intake between individuals receiving hemodialysis in Leicester, UK and Nantong, China. METHODS: The study assessed 40 UK and 44 Chinese participants' dietary intake over a period of 14 days using 24-hour diet recall interviews. Nutritional blood parameters were obtained from medical records. Food consumed by participants in the UK and China was analyzed using the Nutritics and Nutrition calculator to quantify nutritional intake. RESULTS: Energy and protein intake were comparable between UK and Chinese participants, but with both below the recommended daily intake. Potassium intake was higher in UK participants compared to Chinese participants (2,115 [888] versus 1,159 [861] mg/d; P < .001), as was calcium (618 [257] versus 360 [312] mg/d; P < .001) and phosphate intake (927 [485] versus 697 [434] mg/d; P = .007). Vitamin C intake was lower in UK participants compared to their Chinese counterparts (39 [51] versus 64 [42] mg/d; P = .024). Data are reported here as median (interquartile range). CONCLUSION: Both UK and Chinese hemodialysis participants have insufficient protein and energy in their diet. New strategies are required to increase protein and energy intakes. All participants had inadequate daily intake of vitamins C and D; there may well be a role in the oral supplementation of these vitamins, and further studies are urgently needed.