Background Although considered the best means of providing haemodialysis, arteriovenous fistulas (AVFs) may increase long-term cardiovascular morbidity and mortality because of the low peripheral resistance and high cardiac output that develops. We assessed whether a randomised controlled trial (RCT) examining the cardiovascular impact of AVF ligation in stable renal transplant patients was feasible. Methods A parallel two-arm, non-blinded, feasibility trial enrolled forty consenting adult kidney recipients with a patent AVF and with good transplant function (estimated Glomerular Filtration Rate > 35 mL/min/1.73m 2 ) from six UK centres. At baseline, each had maximal oxygen consumption (peak VO 2 ) quantified by cardiopulmonary exercise testing (CPET), and activity levels and other quality of life (QoL) domains assessed by wrist accelerometry and Short Form-36 questionnaire responses. Participants were randomised by a web response system in a 1:1 ratio to surgical disconnection of their AVF (intervention) or to continued conservative management (standard care), stratified according to AVF site (wrist or elbow) and AVF volume flow (low or high). The assessments were repeated six months later. The primary outcome measure was the proportion of approached patients who completed the study, with pre-determined red-amber-green criteria determining progression to the main study. Secondary non-blinded clinical outcome measures included: peak VO 2 ; physical functioning (SF-36 score); total activity levels (mg/day); N-terminal pro B-type natriuretic peptide (NT-proBNP – higher values indicating myocardial overstretch). Key findings The target 40 patients were recruited to the trial and randomised. However, only 27 (67.5%) received the allocated intervention and completed both CPETs, with 7 of 20 (35%) randomised to AVF disconnection not undergoing surgery, below the predetermined completion rate required for trial progression. Compliance to wearing the wrist accelerometers was generally much better. With regards secondary outcome measures, neither peak VO 2 (the proposed primary end-point for the main RCT) nor accelerometry activity levels were increased following AVF disconnection. There were, however, apparent improvements in 6-monthly NT-proBNP levels and physical functioning scores. Conclusions Although based on small numbers of participants, AVF ligation may be associated with improvements in physical functioning and NT-proBNP values. However, the much higher rates of participant drop-out than anticipated (particularly for the intervention group) would make successful delivery of the proposed RCT extremely challenging, with impractically large numbers of participants required. Alternative study designs should be considered. Trial registration number ISRCTN49033491. Trial Funding: National Institute for Health Research (NIHR) Research for Patient Benefit Funding grant (NIHR202255).

Hypertension is extremely common among individuals with kidney disease undergoing haemodialysis, with an estimated prevalence exceeding 80%. However, uncertainties remain on how best to manage hypertension in this group. This review discusses in detail the diagnosis, mechanism, and more importantly the management of hypertension in patients on haemodialysis presented as '10 tips' for easy application in day-to-day clinical practise.

People living with chronic kidney disease (CKD) frequently experience multiple long-term conditions (multimorbidity) and/or frailty. This population is under-researched and shared decision-making in this context is challenging. Clinical guidelines recommend the kidney failure risk equation (KFRE) is used to guide CKD care and referral. This study aims to explore patients’ and healthcare professionals’ (HCPs) perspectives on CKD, including kidney failure risk, and shared decision-making in multimorbidity and/or frailty. A secondary aim is to examine perceptions of KFRE, as a guideline-recommended prognostic tool, in these populations. Semi-structured interviews with patients and focus groups for HCPs from primary and secondary care settings in Glasgow, United Kingdom were conducted March 2024-July 2025. Using a theory-informed abductive approach, data were analysed according to Normalisation Process Theory. Thirty-one patients (aged 46–94 years old; 3–10 long-term health conditions; clinical frailty scale of 1–7) and nineteen HCPs participated. Five interconnected factors shaped understanding of CKD, kidney failure risk and shared decision-making, each experienced differently by patients and HCPs: (1) Variable knowledge of CKD, with many patients unaware of their diagnosis and HCPs recognising challenges within time-pressured consultations or with competing priorities; (2) Workload and burden of managing CKD within multimorbidity, including cognitive, practical and emotional demands for patients and competing priorities and complexity for HCPs; (3) Relationships and interactions, where trust and continuity facilitated shared decision-making; (4) Context and priorities, including prioritisation of CKD by patients and HCPs; and (5) Pervasive uncertainty around prognosis, symptom attribution and when to discuss kidney failure risk. KFRE was unknown to patients and most primary care HCPs, secondary care HCPs had greater awareness but expressed mixed views on its application. CKD was often not a priority for patients or HCPs, compared to other conditions. Many patients wanted to better understand CKD and kidney failure risk alongside other conditions. Trusting relationships, continuity of care and individual priorities were central to shared decision-making, but frequently undermined by system pressures. Methods of communicating kidney failure risk and uncertainty require further research. Findings provide insights for embedding CKD and kidney failure risk understanding into the care of individuals with multimorbidity or frailty. Ethical approval granted in August 2023 by the NHS Health Research Authority following a favourable opinion from the West of Scotland Research Ethics Committee (REC) 3 (IRAS ID: 325848, REC reference: 23WS/0119, Protocol number GN22RE559).

Accurate prediction of diabetic kidney disease progression is challenging, but mandatory. Urinary Dickkopf-3 (uDKK3), a tubular epithelia-derived glycoprotein and marker of tubular injury, is a promising biomarker for kidney function decline. We explored the clinical utility of uDKK3 to predict kidney function decline and adverse cardiovascular events in patients with T2DM in a primary healthcare setting. In this cohort study, 3232 patients with T2DM were analyzed. The primary endpoint was a composite of a sustained eGFR decline ≥40%, a sustained increase in albuminuria of at least 30% including a transition in albuminuria class, progression to ESKD, and death from kidney failure. After adjustment for confounding variables, uDKK3 values >200 pg/g creatinine were associated with a higher risk of the composite kidney endpoint during a median follow-up of 4.26 years. Furthermore, uDKK3 improved the prediction of the 1-year eGFR decline on top of albuminuria. Individuals with high uDKK3 levels also had an increased risk for adverse cardiovascular events and all-cause mortality. uDKK3 identifies patients with T2DM at high risk for kidney function decline on top of established biomarkers (albuminuria and eGFR). In primary care, uDKK3 may help to identify high-risk patients who might benefit from intensified treatment and/or referrals to specialists.

Importance:Approximately 10% to 15% of patients with advanced chronic kidney disease (CKD) experience a fatal or nonfatal cardiovascular event annually. The effects of antithrombotic therapies on cardiovascular events in patients with advanced CKD are unknown. Objective:To determine whether low-dose rivaroxaban reduces rates of adverse cardiovascular events compared with placebo in patients with advanced CKD. Design, Setting, and Participants:Randomized, double-blind, placebo-controlled trial conducted at 90 centers in 12 countries. Eligible participants were adults with CKD stage 4 or 5 and patients with dialysis-dependent kidney failure. Participants had a history of either coronary artery disease; nonhemorrhagic, nonlacunar stroke; peripheral artery disease; diabetes; or were 65 years or older. Enrollment occurred between January 2021 and July 2025. The trial was stopped early on August 7, 2025, for lack of efficacy. Final follow-up occurred on October 30, 2025. Statistical analyses were conducted in February and March 2026. Interventions:Patients were randomized 1:1 to receive rivaroxaban 2.5 mg twice daily or placebo. Main Outcomes and Measures:The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, or a peripheral artery disease event. The primary safety outcome was major bleeding. Results:Of 1458 randomized patients (mean [SD] age, 63.2 [11.6] years, 432 [29.6%] female), 1360 (93.3%) completed follow-up. During a median follow-up of 1.7 years, the primary outcome occurred in 164 patients (22.6%) in the low-dose rivaroxaban group and 151 (20.7%) in the placebo group (13.0 vs 11.8 events per 100 person-years; hazard ratio, 1.09 [95% CI, 0.87-1.36]; P = .46). Major bleeding occurred in 64 patients (8.8%) receiving low-dose rivaroxaban and 44 (6.0%) receiving placebo (5.1 vs 3.4 events per 100 person-years; hazard ratio, 1.51 [95% CI, 1.02-2.22]; P = .04). Conclusions and Relevance:In patients with advanced CKD at high cardiovascular risk, low-dose rivaroxaban did not reduce the risk of a composite cardiovascular outcome. Major bleeding rates were significantly higher in the low-dose rivaroxaban group compared with the placebo group. Trial Registration:ClinicalTrials.gov Identifier: NCT03969953.

Purpose: Vitamin K2 supplementation has emerged as a strategy to enhance recovery and modulate post-exercise physiological responses. This study aimed to assess the effects of vitamin K2 on recovery from muscle-damaging exercise in young and older adults. Methods: Healthy young (18-40 years) and older (65+ years) adults were randomly assigned to either vitamin K2 (menaquinone 7, MK-7, 240 μg/day) or placebo (cellulose) for 12 weeks in this double-blind randomised controlled trial. Before and after supplementation, knee extensor maximal torque, functional ability, muscle soreness, and systemic blood markers of muscle damage and inflammation were measured before (0h) and 3h, 24h, 48h, and 72h post-exercise. Data were analysed using regression and mixed models. Results: Seventy-one participants (35 young and 36 older) completed the study, with 12 weeks of vitamin K2 supplementation increasing circulating MK-7 levels (p-value <0.001). There were no supplement*time effects for any variables. Significant supplement*time*older age interaction effects were noted for electromechanical delay (EMD) (p-value = 0.03), electromyography root mean square (RMS) (p-value = 0.01), IL-6 concentrations (p-value <0.001), and creatine kinase (CK) levels (p-values = 0.02). In older adults, after 12 weeks, EMD appeared lower at all time points and RMS higher post exercise in the vitamin K2 group. No clear pattern in IL-6 or CK were observed, but at 72h post-exercise CK was lower in older adults in the Vitamin K2 group. Conclusions: Vitamin K2 supplementation had no effect on muscle strength, physical function, muscle soreness or inflammatory responses in the recovery period after a bout of resistance exercise. Effects of supplementation were observed on EMD, RMS, IL-6 and CK by age, and warrant further investigation. Trial registration: Prospectively registered on 21st December 2020, trial registration clinicaltrials.gov ID NCT04676958 https://clinicaltrials.gov/ct2/show/NCT04676958.

Chronic kidney disease (CKD) is a major public health concern, closely linked to an increased risk of cardiovascular disease (CVD), which remains the leading cause of morbidity and mortality in this population. While traditional risk factors such as hypertension and diabetes are prevalent in CKD, disease-specific mechanisms-including chronic inflammation, oxidative stress, mineral disturbances and the accumulation of uraemic toxins-further amplify cardiovascular vulnerability. In CKD, both the abundance and molecular cargo of circulating extracellular vesicles (EVs) are altered, reflecting the underlying metabolic and inflammatory milieu. These EVs propagate endothelial dysfunction, vascular calcification, inflammation, thrombosis and cardiac remodelling by transferring bioactive molecules such as proteins and microRNAs to target cells. Emerging evidence suggests that EVs not only serve as biomarkers for early detection and risk stratification of CVD in CKD but may also represent novel therapeutic targets. Preclinical studies demonstrate the potential of stem cell-derived and engineered EVs to promote cardiac repair and modulate pathological signalling. However, translation into clinical practice requires rigorous standardization, safety validation and well-designed human trials. This review synthesizes current knowledge on the mechanisms by which EVs bridge renal dysfunction and cardiovascular pathology, discusses their utility as biomarkers and outlines a research agenda for harnessing their therapeutic potential in CKD-associated CVD.

Chronic kidney disease (CKD) has emerged as a critical global public health concern. This condition is strongly associated with an increased risk of atherosclerotic cardiovascular disease and acute coronary syndromes (ACSs), which have been recently renamed as acute myocardial ischaemic syndromes (AMIS). In CKD patients, the atypical presentation of symptoms complicates the diagnosis and management of angina, a condition that can, if not promptly addressed, rapidly progress to myocardial infarction (MI). Traditional diagnostic tools, such as the electrocardiogram and cardiac biomarkers, are less reliable in this population due to CKD-related baseline alterations, necessitating advanced imaging techniques for accurate assessment. Management strategies for transient myocardial ischaemia in CKD must also carefully balance the risk related to myocardial ischaemia against potential complications from invasive procedures, such as further renal impairment and bleeding. Tailored therapeutic approaches, including adjusted medication regimens and innovative revascularization techniques, are crucial to improve outcomes in this high-risk population. Additionally, asymptomatic MI is notably prevalent in CKD, often remaining undetected and posing significant prognostic implications. The interplay of traditional and non-traditional risk factors, such as uraemia-induced toxicity and chronic inflammation, further exacerbates the risk for plaque instability in CKD patients. This review highlights the necessity of a multidisciplinary approach in managing myocardial ischaemia in CKD, incorporating meticulous risk stratification and personalized treatment plans.

BACKGROUND AND HYPOTHESIS:Guidelines recommend using risk prediction models for predicting kidney failure in chronic kidney disease (CKD). Many people with CKD have multiple long-term conditions (multimorbidity), which influences outcomes including kidney failure and mortality. This study validated the four-variable kidney failure risk equation (KFRE) in individuals with CKD, with and without multimorbidity, comparing performance of KFRE using creatinine and cystatin C to calculate estimated glomerular filtration rate (eGFR) and updated the model to account for competing mortality risks. METHODS:Observational cohort study using research-based (UK Biobank) and population-based cohorts (Stockholm Creatinine Measurements project: SCREAM). Multimorbidity was defined as two or more long-term conditions in addition to CKD. Kidney failure was defined as long-term dialysis or kidney transplantation. KFRE performance assessment included discrimination, calibration, and overall fit at 2 and 5 years. An updated model (using the same variables as KFRE) accounting for competing mortality risks was developed and validated. RESULTS:14 998 of 24 489 individuals in UK Biobank (61.2%) and 30 147 of 42 902 individuals in SCREAM (70.3%) had multimorbidity. Discrimination of KFRE was good (area under curve $\ge $0.86 across eGFR equations in all cohorts, multimorbidity groups and time horizons). Kidney failure risk was under-estimated in people with multimorbidity in UK Biobank (observed/expected (O/E) ratio 1.75 at 5 years; eGFR creatinine). Conversely, calibration-in-the-large (O/E ratio) at 5 years in SCREAM was 1.05 in the multimorbidity group (eGFR creatinine). Using cystatin C compared to creatinine did not improve model performance.Cumulative incidence of death was higher with multimorbidity compared to no multimorbidity. An updated model considering competing mortality improved calibration performance over KFRE, O/E ratio 0.98 in multimorbidity group of the validation cohort (UK Biobank) at 5 years. CONCLUSION:Competing mortality risk is important when predicting kidney failure, particularly for people with multimorbidity. An updated model accounting for competing mortality risk, permits improved model performance.

Diuretic resistance in worsening heart failure (HF) is associated with poorer outcomes and, although common, can be challenging to identify. The recently developed BAN-ADHF score can potentially identify patients with worsening HF at risk of diuretic resistance. We externally validated the BAN-ADHF diuretic-resistance score in a multicentre randomized trial comparing adjunctive dapagliflozin to metolazone in patients with HF and diuretic resistance. We calculated a seven-variable modified BAN-ADHF score at baseline and dichotomised patients by the median BAN-ADHF score (8). We assessed loop diuretic efficiency (kg weight change per 40-mg furosemide) and decongestion (weight, eight-zone lung ultrasound B-lines, clinical congestion score) over 96 h. A baseline score ≥8 identified lower loop diuretic efficiency (pooled difference -0.12 kg/40 mg, 95% CI -0.18 to -0.06; p < 0.001) despite similar congestion markers at baseline. The BAN-ADHF score may be useful clinically to identify patients at risk of diminished response to diuretics.

Abstract Background Chronic conditions often cluster together, forming distinct multimorbidity patterns. We aimed to explore how such patterns are associated with the risk of albuminuria. Methods We utilized the Stockholm Creatinine Measurements (SCREAM) project, comprising 675,570 adults undergoing outpatient albuminuria testing in Stockholm, Sweden. Disease patterns were derived in adults without albuminuria at baseline, stratified by age (18–64, 65–74, ≥ 75 years). Associations with incident albuminuria (albumin-creatinine ratio > 30 mg/g) and macroalbuminuria (> 300 mg/g) were examined using Cox and Fine-Gray competing risk models. Results We identified four multimorbidity patterns in younger participants (18–64), six in the 65–74 group, and seven among those aged ≥ 75. Across all age groups, most patterns—including cardiovascular, mental health, and eye patterns—were consistently associated with elevated albuminuria risk compared to those without multimorbidity. In the 65–74 stratum, the cardiovascular pattern had the highest risk compared to those without multimorbidity (HR 3.09: 95% CI: 2.85–3.34). Among those aged ≥ 75, almost all identified patterns showed higher risk, with those in the vascular pattern being at highest risk (HR: 2.41, 95% CI: 2.08–2.80). The dementia pattern showed no significant association. High-burden patterns in older participants with numerous chronic conditions (e.g., multisystem and cardiovascular patterns) were at increased risk, but this was attenuated after accounting for the competing risk of death. The 5- to 6-year cumulative incidence of albuminuria exceeded 10–14% in the highest-risk patterns, 5–9% higher than for those without multimorbidity. In interaction analyses, reduced estimated glomerular filtration rate amplified risk among younger individuals. Females generally had lower risk, except with mental health patterns in younger ages or cardiovascular multimorbidity in those 65 to 74. Conclusions Multimorbidity patterns, including those characterized by non-traditional CKD risk factors, can help identify individuals at elevated albuminuria risk. Targeted screening of these groups may enable preventive strategies to slow or prevent kidney damage.

Importance: Approximately 10% to 15% of patients with advanced chronic kidney disease (CKD) experience a fatal or nonfatal cardiovascular event annually. The effects of antithrombotic therapies on cardiovascular events in patients with advanced CKD are unknown. Objective: To determine whether low-dose rivaroxaban reduces rates of adverse cardiovascular events compared with placebo in patients with advanced CKD. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled trial conducted at 90 centers in 12 countries. Eligible participants were adults with CKD stage 4 or 5 and patients with dialysis-dependent kidney failure. Participants had a history of either coronary artery disease; nonhemorrhagic, nonlacunar stroke; peripheral artery disease; diabetes; or were 65 years or older. Enrollment occurred between January 2021 and July 2025. The trial was stopped early on August 7, 2025, for lack of efficacy. Final follow-up occurred on October 30, 2025. Statistical analyses were conducted in February and March 2026. Interventions: Patients were randomized 1:1 to receive rivaroxaban 2.5 mg twice daily or placebo. Main Outcomes and Measures: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, or a peripheral artery disease event. The primary safety outcome was major bleeding. Results: Of 1458 randomized patients (mean [SD] age, 63.2 [11.6] years, 432 [29.6%] female), 1360 (93.3%) completed follow-up. During a median follow-up of 1.7 years, the primary outcome occurred in 164 patients (22.6%) in the low-dose rivaroxaban group and 151 (20.7%) in the placebo group (13.0 vs 11.8 events per 100 person-years; hazard ratio, 1.09 [95% CI, 0.87-1.36]; P = .46). Major bleeding occurred in 64 patients (8.8%) receiving low-dose rivaroxaban and 44 (6.0%) receiving placebo (5.1 vs 3.4 events per 100 person-years; hazard ratio, 1.51 [95% CI, 1.02-2.22]; P = .04). Conclusions and Relevance: In patients with advanced CKD at high cardiovascular risk, low-dose rivaroxaban did not reduce the risk of a composite cardiovascular outcome. Major bleeding rates were significantly higher in the low-dose rivaroxaban group compared with the placebo group. Trial Registration: ClinicalTrials.gov Identifier: NCT03969953.

submission trends to the ERA Congress provide a valuable lens through which to observe the evolution of nephrology research and education. Analysing submissions from 2020 to 2026, we document a marked recovery following the COVID-19 disruption, culminating in a record number of abstracts for the 2026 Congress in Glasgow. Beyond volume, notable shifts have occurred in subject mix, geographic participation and reviewer scoring patterns. Chronic kidney disease and glomerular disorders now dominate submissions, reflecting major scientific advances and changing clinical priorities, while international engagement has broadened substantially. These trends suggest that the ERA Congress has entered a new phase characterised by sustained high activity rather than transient post-pandemic rebound. We discuss the implications for congress programme design, peer review, inclusiveness and future strategic planning, highlighting how abstract data can inform the direction of large scientific meetings and the nephrology community at large.

Kidney transplantation markedly improves survival and quality of life in patients with kidney failure, yet cardiovascular (CV) disease remains the leading cause of morbidity and mortality in kidney transplant recipients (KTRs). This review outlines the complex interplay of traditional, transplant-specific and recipient- and donor-related risk factors that sustain a high CV burden post-transplantation. While kidney function restoration reduces uremic toxins and improves cardiometabolic parameters, new challenges arise from immunosuppressive therapies, persistent hypertension, post-transplant diabetes mellitus and chronic inflammation. Common CV complications include coronary artery disease, heart failure, valvular disease, peripheral artery disease and refractory hypertension. Risk stratification tools and guidelines often fail to account for transplant-specific variables, resulting in suboptimal management. Although some pharmacological strategies and careful antihypertensive regimens show promise, most evidence is extrapolated from non-transplant populations due to the lack of dedicated randomized controlled trials. Emerging therapies like sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists hold potential but require further validation in this population. Moreover, sex disparities persist in access to transplantation and in post-transplant outcomes, with men generally experiencing higher CV risk but women potentially facing greater relative mortality. The review underscores the urgent need for transplant-specific CV research, personalized therapeutic strategies including precision medicine and greater inclusion of women in research. Optimizing CV outcomes in KTRs will require multidisciplinary collaboration, rigorous evidence generation, and an integrated approach to risk prediction, prevention and treatment.

Objective Physical activity (PA) has been generally recognised as beneficial for health. The effect of a change in PA on kidney biomarkers in healthy individuals without kidney disease remains unclear. This manuscript synthesised the evidence of the association of changes in PA with kidney biomarkers in the general population free from kidney disease.Design Systematic review and meta-analysis.Data sources Embase, PubMed, MEDLINE and Web of Science databases were searched from inception to 12 March 2023.Eligibility criteria for selecting studies Studies of longitudinal or interventional design were selected initially. The following studies were excluded: (1) case-control studies, (2) studies where PA was measured at a single time point, (3) populations with known kidney disease, (4) studies evaluating the impact of a single episode/event of PA and (5) non-English language studies.Data extraction and synthesis Two independent reviewers extracted data from a pre-designed table and assessed the risk of bias using the Cochrane Risk of Bias tool. Data were pooled using a random-effects model. Hedge’s g was used to synthesise effect sizes and obtain an overall estimate. Heterogeneity between studies was measured using I2. Funnel plots and Egger’s test were performed to evaluate the risk of biased results.Results 16 interventional studies with randomised or non-randomised designs involving 500 participants were identified. The median follow-up was 84 days. 10 studies were at high risk of bias. Studies with low quality were published prior to the year 2000. Changes in PA were found only to have a positive association with serum creatinine (SCr) (Hedge’s g=0.69; 95% CI 0.13, 1.24; I2=81.37%) and not with plasma renin activity (PRA), urea, or urine albumin-to-creatinine ratio (UACR). The positive association was only observed in people with obesity and those who exercised for more than 84 days.Conclusions Higher levels of PA are associated with increased SCr levels in healthy people. It remains unclear if this association is related to impaired kidney function or gain in muscle mass, as data on other kidney biomarkers did not support a certain link.PROSPERO registration number This review has been registered on PROSPERO (CRD42023407820).