BACKGROUND:For older people and those with more comorbidities, kidney replacement therapy may not offer a mortality benefit. Conservative kidney management represents an alternative treatment pathway for kidney failure without dialysis. OBJECTIVES:To identify the clinical and socioeconomic factors associated with choosing a non-dialysis care pathway and to explore geographical variation. METHODS:MEDLINE, Embase and Web of Science databases were searched. Studies, which included patients with kidney failure choosing non-dialysis care and a comparator group of patients preparing for or receiving kidney replacement therapy, were selected. Exposures included clinical and socioeconomic factors. The outcome was a choice to have non-dialysis care. Random-effects meta-analysis was performed; with subgroup analysis by region. RESULTS:In total 43 studies, including 51,872 participants, were selected. Female sex was associated with choosing non-dialysis care (pooled OR 1.47, 95% CI 1.26-1.71). There was no overall association between non-white ethnicity and treatment choice in Western countries. However, in North America non-White groups had lower odds of receiving non-dialysis care compared to white patients (OR 0.70, 95% CI 0.60-0.81). Socioeconomic deprivation was associated with choosing non-dialysis care in Asia, as was low educational attainment (OR 2.85, 95% CI 1.54-5.26). There was an overall association between living alone and non-dialysis care (pooled OR 1.55, 95% CI 1.24-1.93). CONCLUSION:The geographical variation in these results highlights the importance of social and political context in understanding treatment access. We identify living alone and low socioeconomic status as possible predictors of choosing non-dialysis care. This analysis cannot ascertain if these associations arise from appropriate shared decisions, challenges to the decision making process or barriers to accessing kidney replacement therapy. Nevertheless, this review illustrates the interplay of socioeconomic, interpersonal and systemic factors at play and lays the foundation to unravelling these complexities.

Little is known about trajectory of frailty as patients with advanced chronic kidney disease transition onto dialysis. This retrospective cohort study aims to describe change in frailty from dialysis initiation over the course of the first year of treatment. Secondly, we aim to examine the association of frailty and change in frailty over time with mortality and hospitilisation. The study included incident haemodialysis or peritoneal dialysis patients. Clinical frailty scale (CFS) was recorded at dialysis start and after 6 and 12 months of treatment. Multilevel mixed effects linear regression models were used to examine change in CFS from baseline to 6 and 12 months after start of dialysis. Kruskal-Wallis tests were used to assess the association between CFS with number of hospitilisations. Cox proportional hazard models were used to examine the association of CFS with survival time after dialysis initiation. The study included 293 patients, 65% haemodialysis, 35% peritoneal dialysis. Characteristics of the patients on each modality were similar. Mean CFS pre-dialysis was 4.0 (95% CI 3.81–4.21). Time on dialysis was associated with a mean increase in CFS of 0.18 per 6 months (95% CI 0.06 to 0.31), independent of confounding variables. Frailty prior to initiation of dialysis (defined as CFS ≥ 5) was associated with increased hospitilisations, compared to the non-frail group (p = 0.011). An increase in frailty score between pre-dialysis and 6 months was associated with increased risk of mortality (HR 1.35, 95% CI 1.01–1.80). Our findings highlight the importance of pre-dialysis frailty screening in order to identify at-risk patients and inform prognosis and patient counselling. Frailty trajectory in the first 6 months of dialysis treatment is a predictor of adverse outcomes.

Introduction: Glucocorticoids (GCs) are pivotal in treating antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV); however, their use is associated with significant toxicities. Findings of recent trials support reduced GC dosing, demonstrating efficacy with fewer adverse events. Methods: This was a retrospective cohort study evaluating long-term outcomes of a rapid taper GC regimen in severe AAV. Fifty-eight patients treated with combination rituximab, low-dose i.v. cyclophosphamide, and a limited course of GC (total equivalent prednisolone: 1148 [887–1390] mg; median duration of GC: 14 [7–15] days) were followed-up with for a median of 41 (interquartile range: 27–48) months. Results: Median Birmingham Vasculitis Activity Score (BVAS), serum creatinine, estimated glomerular filtration rates (eGFR), and urinary protein-to-creatinine ratio (uPCR) at presentation were 14 (12–18), 176 (132–270) μmol/l, 29 (19–50) ml/min per 1.73 m2, and 152 (77–289) mg/mmol, respectively. At 3 months, 51 of 58 (88%) achieved remission without additional GC treatment, and this was sustained in 49 of 56 (88%) at 1 year, with improved kidney parameters (creatinine: 109 [83–162] μmol/l, eGFR: 54 [37–74]ml/min per 1.73 m2, uPCR: 35 [12–94] mg/mmol at 12 months). At 3 years, kidney and overall survival were 33 of 35 (94%) and 35 of 38 (93%), respectively; and 27 of 35 (77%) were in sustained remission without additional GC. Early improvements in disease activity and kidney function—and in long-term kidney and patient survival—were comparable with a previous cohort treated with an equivalent rituximab-cyclophosphamide regimen and a conventional GC taper, whereas adverse events (infection, new-onset diabetes) were less frequent. Conclusion: Ultrarapid GC withdrawal is safe and effective for many patients with AAV when used with combination induction regimens. This approach warrants confirmatory controlled studies and may have a place in the current management of patients at high risk of GC toxicities.

Glucocorticoids (GCs) are pivotal in treating antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV); however, their use is associated with significant toxicities. Findings of recent trials support reduced GC dosing, demonstrating efficacy with fewer adverse events. This was a retrospective cohort study evaluating long-term outcomes of a rapid taper GC regimen in severe AAV. Fifty-eight patients treated with combination rituximab, low-dose i.v. cyclophosphamide, and a limited course of GC (total equivalent prednisolone: 1148 [887-1390] mg; median duration of GC: 14 [7-15] days) were followed-up with for a median of 41 (interquartile range: 27-48) months. Median Birmingham Vasculitis Activity Score (BVAS), serum creatinine, estimated glomerular filtration rates (eGFR), and urinary protein-to-creatinine ratio (uPCR) at presentation were 14 (12-18), 176 (132-270) μmol/l, 29 (19-50) ml/min per 1.73 m2, and 152 (77-289) mg/mmol, respectively. At 3 months, 51 of 58 (88%) achieved remission without additional GC treatment, and this was sustained in 49 of 56 (88%) at 1 year, with improved kidney parameters (creatinine: 109 [83-162] μmol/l, eGFR: 54 [37-74]ml/min per 1.73 m2, uPCR: 35 [12-94] mg/mmol at 12 months). At 3 years, kidney and overall survival were 33 of 35 (94%) and 35 of 38 (93%), respectively; and 27 of 35 (77%) were in sustained remission without additional GC. Early improvements in disease activity and kidney function-and in long-term kidney and patient survival-were comparable with a previous cohort treated with an equivalent rituximab-cyclophosphamide regimen and a conventional GC taper, whereas adverse events (infection, new-onset diabetes) were less frequent. Ultrarapid GC withdrawal is safe and effective for many patients with AAV when used with combination induction regimens. This approach warrants confirmatory controlled studies and may have a place in the current management of patients at high risk of GC toxicities.

Abstract Background Chronic kidney disease (CKD) prevalence is steadily increasing, in part due to increased multimorbidity in our aging global population. When progression to kidney failure cannot be avoided, people need unbiased information to inform decisions about whether to start dialysis, if or when indicated, or continue with holistic person-centred care without dialysis (conservative kidney management). Comparisons suggest that while there may be some survival benefit from dialysis over conservative kidney management, in people aged 80 years and over, or with multiple health problems or frailty, this may be at the expense of quality of life, hospitalisations, symptom burden and preferred place of death. Prepare for Kidney Care aims to compare preparation for a renal dialysis pathway with preparation for a conservative kidney management pathway, in relation to quantity and quality of life in multimorbid, frail, older people with advanced CKD. Methods This is a two-arm, superiority, parallel group, non-blinded, individual-level, multi-centre, pragmatic trial, set in United Kingdom National Health Service (NHS) kidney units. Patients with advanced CKD (estimated glomerular filtration rate < 15 mL/min/1.73 m2, not due to acute kidney injury) who are (a) 80 years of age and over regardless of frailty or multimorbidity, or (b) 65–79 years of age if they are frail or multimorbid, are randomised 1:1 to ‘prepare for responsive management’, a protocolised form of conservative kidney management, or ‘prepare for renal dialysis’. An integrated QuinteT Recruitment Intervention is included. The primary outcome is mean total number of quality-adjusted life years during an average follow-up of 3 years. The primary analysis is a modified intention-to-treat including all participants contributing at least one quality of life measurement. Secondary outcomes include survival, patient-reported outcomes, physical functioning, relative/carer reported outcomes and qualitative assessments of treatment arm acceptability. Cost-effectiveness is estimated from (i) NHS and personal social services and (ii) societal perspectives. Discussion This randomised study is designed to provide high-quality evidence for frail, multimorbid, older patients with advanced CKD choosing between preparing for dialysis or conservative kidney management, and healthcare professionals and policy makers planning the related services. Trial registration ISRCTN, ISRCTN17133653 (https://doi.org/10.1186/ISRCTN17133653). Registered 31 May 2017.

Frailty is a condition that is frequently observed among patients performing dialysis. It is characterised by a decline in both physiological and cognitive state, leading to a combination of symptoms such as weight loss, exhaustion, low physical activity, weakness, and slow walking speed. Frail patients not only experience a poor quality of life, but they are also at a higher risk of hospitalization, infection, cardiovascular events, dialysis-associated complications, and death.Frailty occurs as a result of a combination and interaction of various medical issues in patients who are on dialysis. Unfortunately, there is no cure for frailty. To address frailty, a multifaceted approach is necessary, involving coordinated efforts from nephrologists, geriatricians, nurses, allied health practitioners, and family members. Strategies such as optimizing nutrition and CKD-related complications, reducing polypharmacy by deprescription, personalized dialysis prescription and considering home-based or assisted dialysis may help slow the decline of physical function over time in subjects with frailty.This review discusses the underlying causes of frailty in patients on dialysis and examines the methods and difficulties involved in managing frailty among this group.

ABSTRACT Background Renal supportive care has become an increasingly relevant treatment option as the renal patient population ages. Despite the prevalence of kidney disease amongst ethnic minority and socioeconomically deprived patients, evidence focused on supportive care and dialysis decision-making in these groups is limited. Methods This retrospective study selected older patients referred to a low clearance or supportive care service between 1 January 2015 and 31 December 2019. A descriptive analysis of clinical and socioeconomic characteristics according to treatment choice was produced and multivariate logistic regression models used to identify predictive factors for choosing supportive care. Surrogate markers for the success of decision-making processes were evaluated, including time taken to reach a supportive care decision and risk of death without making a treatment decision or within 3 months of starting kidney replacement therapy (KRT). Finally, the association between ethnicity and socioeconomic status and hospital admission rates was compared between treatment groups. Results Amongst 1768 patients, 515 chose supportive care and 309 chose KRT. Predictive factors for choosing supportive care included age, frailty and a diagnosis of cognitive impairment. However, there was no association with ethnicity or deprivation. Similarly, these factors were not associated with time taken to make a supportive care decision or the mortality outcome. Amongst those on KRT, more socially advantaged patients had decreased rates of hospital admissions compared with those less advantaged (incident rate ratio 0.96, 95% confidence interval 0.92–0.99). Conclusion Predictive factors for choosing supportive care were clinical, rather than socioeconomic. Lower socioeconomic status was associated with increased rates of hospitalization in the KRT group. This is a possible signal that these groups experienced greater morbidity on KRT versus supportive care, an association not demonstrated amongst higher socioeconomic groups.

Rapid advances in molecular biology, imaging, and data science are transforming the way urologists and nephrologists conceptualize disease, moving from organ-based descriptions to mechanistically defined, precision phenotypes. In prostate, bladder, and renal cancers, genomic and metabolic profiling now refine risk stratification and guide targeted therapeutics, while artificial intelligence (AI)–enabled imaging modalities such as multiparametric MRI and PSMA PET-CT are reshaping diagnostic pathways and treatment planning. In parallel, the nephrology community is redefining chronic kidney disease (CKD) using novel biomarkers and AI-based prediction models that move beyond creatinine and estimated glomerular filtration rate to capture early injury, ageing biology, and complex comorbidity patterns. These editorial frames these converging trends as an integrated “uro-kidney continuum”, arguing that urology and nephrology must co-develop diagnostics, therapeutics, and data infrastructures. The Uroscience aims to become a dedicated platform for this convergence, championing translational science, methodological rigor, and ethically grounded implementation.

Background We report results from a phase II randomised placebo-controlled trial assessing zibotentan, a highly selective endothelin receptor antagonist (ERA), in chronic kidney disease (CKD) secondary to systemic sclerosis (SSc). Methods This trial included three sub-studies: ZEBRA 1—a randomised placebo-controlled, double-blind trial of zibotentan in SSc patients with CKD2 or CKD3 (and glomerular filtration rate (GFR) >45 ml/min) over 26 weeks; ZEBRA 2A—a 26-week placebo-controlled, single-blind trial of zibotentan in scleroderma renal crisis patients not requiring dialysis; and ZEBRA 2B—an open label pharmacokinetic study of zibotentan in patients on haemodialysis. Results Sixteen patients were screened for ZEBRA 1. Of these, 6 patients were randomised to zibotentan and 7 to placebo. In ZEBRA 1, there were 47 non-serious adverse events (AE) during the trial. Twenty-seven occurred in the placebo group and 20 in the zibotentan group. One serious adverse event (SAE) occurred during ZEBRA1, in the placebo arm. Descriptive statistics did not suggest an effect of study drug on serum sVCAM1. Estimated GFR numerically declined in patients treated with placebo at 26 weeks and 52 weeks. In contrast, average eGFR increased in zibotentan-treated cases. The 4 patients in ZEBRA 2A experienced 8 non-serious AEs, distributed equally between placebo and zibotentan. There was one SAE each in placebo and zibotentan groups, both unrelated to study medication. ZEBRA 2B recruited 8 patients, 6 completed first dosing, and 2 completed a second dosing visit. Pharmacokinetic analysis confirmed zibotentan levels within the therapeutic range. Three patients experienced 3 non-serious AEs. One SAE occurred and was unrelated to study drug. Conclusions Zibotentan was generally well-tolerated. ZEBRA 1 did not show any effect of zibotentan on serum sVCAM-1 but was associated with numerical improvement in eGFR at 26 weeks that was more marked at 52 weeks. ZEBRA 2B suggested a feasible dose regimen for haemodialysis patients. Trial registration EudraCT no: 2013-003200-39 (first posted January 28, 2014) ClinicalTrials.gov Identifier: NCT02047708 Sponsor protocol number: 13/0077

Author: Royal Free Hospital, London, UK plans were not considered appropriately on a frequent basis for renal inpatients. The most common barriers cited to hindering ACP discussions were limited time to explore such issues and anxieties relating to inciting fear or anger in patients and key contacts. Most respondents felt very confident in their ability to explore current medical issues (80%) and co-morbidities (76%) but less than twothirds expressed similar confidence in assessments of physiological baseline (48%), functional baseline (56%), frailty (52%) and prognosis (24%). The survey also identified problems with documentation of TEP and resuscitation plans on our electronic patient record (EPR) system and access to community records for pre-existing ACP.

Background We describe efforts at one tertiary university teaching hospital to rapidly recruit, train and deploy medical students into paid clinical support worker roles during the COVID-19 pandemic. Methods Recruitment was conducted by means of a single email outlining the emergent clinical situation and specifying role descriptions, terms and conditions, and temporary staff enrolment paperwork. Applicants could begin work provided they were in good standing and received departmental orientation. Student representatives liaised with teaching faculty and participating departments. Roles were modified in response to student and departmental feedback. Results Between 25 December 2020 and 9 March 2021, 189 students contributed 1335 shifts, providing 10 651 hours of clinical care in total. The median number of shifts worked per student was 6 (mean: 7; range: 1-35). Departmental leaders attested that the student workers eased the burden on hospital nursing teams. Conclusion Medical students contributed usefully and safely to the provision of healthcare within well-defined and supervised clinical support worker roles. We propose a model of working which could be adapted in the event of future pandemics or major incidents. The pedagogical value to medical students of working in clinical support roles warrants closer evaluation.

Abstract Objectives Cocaine and cocaine mixed with levamisole are increasingly used in the UK and result in significant direct nasal damage in addition to promoting vasculitis. Our aims were as follows: (1) to identify the main symptoms and presentation of cocaine-induced vasculitis; (2) to provide evidence regarding the best practice for the investigation and diagnosis of cocaine-induced vasculitis; and (3) to analyse the clinical outcomes of patients in order to understand the optimal management for the condition. Methods We performed a retrospective case series analysis of patients presenting with cocaine-induced midline destructive lesions or vasculitis compatible with granulomatosis with polyangiitis (GPA) from two large tertiary vasculitis clinics between 2016 and 2021. Results Forty-two patients (29 Birmingham, 13 London) with cocaine-induced midline lesions or systemic disease were identified. The median age was 41 years (range 23–66 years). Current cocaine use was common, and 20 of 23 samples provided were positive when routine urine toxicology was performed; 9 patients who denied ever using cocaine were identified as using cocaine based on urine toxicology analysis, and 11 who stated they were ex-users still tested positive. There was a high incidence of septal perforation (75%) and oronasal fistula (15%). Systemic manifestations were less common (27%), and only one patient had acute kidney injury. Fifty-six per cent of our patients were PR3-ANCA positive, with none testing positive for MPO-ANCA. Symptom remission required cocaine discontinuation even when immunosuppression was administered. Conclusion Patients with destructive nasal lesions, especially young patients, should have urine toxicology performed for cocaine before diagnosing GPA and considering immunosuppressive therapy. The ANCA pattern is not specific for cocaine-induced midline destructive lesions. Treatment should be focused on cocaine cessation and conservative management in the first instance in the absence of organ-threatening disease.

Shared decision making in advanced chronic kidney disease (CKD) requires unbiased information on survival and person-centred outcomes known to matter to patients: quality of life, symptom burden and support from family and healthcare professionals. To date, when deciding between dialysis and conservative care, patients have had to rely on evidence from small observational studies. Clinicians recognize that like is not being compared with like in these studies, and interpret the results differently. Furthermore, support differs considerably between renal units. What patients choose therefore depends on which renal unit they attend. To address this, a programme of work has been underway in the UK. After reports on survival and symptoms from a small number of renal units, a national, mixed-methods study-the Conservative Kidney Management Assessment of Practice Patterns Study-mapped out conservative care practices and attitudes in the UK. This led to the Prepare for Kidney Care study, a randomized controlled trial comparing preparation for dialysis versus preparation for conservative care. Although powered to detect a positivist 0.345 difference in quality-adjusted life years between the two treatments, this trial also takes a realist approach with a range of person-centred secondary outcomes and embedded qualitative research. To understand generalizability, it is nested in an observational cohort study, which is nested in a CKD registry. Challenges to recruitment and retention have been rapidly identified and addressed using an established embedded mixed methods approach-the QuinteT recruitment intervention. This review considers the background to and progress with recruitment to the trial.

A 64-year-old man with granulomatosis with polyangiitis (GPA) reported feeling "below par." Almost 2 years earlier, he had presented with nasal crusting, epistaxis, deafness, weight loss, night sweats, and nonvisible hematuria. No baseline imaging was performed. Cytoplasmic anti-neutrophil cytoplasmic antibody was positive with anti–proteinase-3 (PR3) titer 35 U/l and C-reactive protein (CRP) 6 mg/l, peaking a month later at 68 U/l and 51 mg/l, respectively. He was treated with prednisolone for 2.5 months, with little response.

Objective. Renal involvement is common in systemic sclerosis (scleroderma; SSc) and includes chronic kidney disease (CKD). We have performed analysis of urinary proteins to gain insight into local molecular pathology of CKD in SSc and identify candidate markers for use in clinical trials. Methods. To evaluate urinary proteins that might specifically reflect SSc-related CKD, patients were recruited with confirmed SSc and stratified for the presence or absence of CKD. Controls included patients with CKD and no SSc, in addition to healthy volunteers. Candidate markers were measured in serum and urine by multiplex immunoassay testing for IL6, IL18, TNF-alpha, monocyte chemoattractant protein 1 (MCP1), monocyte chemoattractant protein 3 (MCP3), VEGF and the soluble adhesion molecules vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). Results. One hundred and two subjects were examined, including patients with SSc with no evidence of CKD (n = 40), SSc with CKD (n = 39), non-SSc CKD (n = 11) and healthy volunteers (n = 12). Urinary levels of IL6, MCP1, TNF-alpha, MCP3, IL18 and ICAM-1 were elevated in SSc patients compared with healthy controls. The most significant differences were for MCP1 and ICAM-1 (both P<0.0001), and these analytes also showed the most significant differences between groups overall (P = 0.003 for MCP1 and P<0.0001 for ICAM-1). These markers showed a trend (MCP1, P = 0.0868) or a significant difference (ICAM-1, P = 0.0134) between SSc-CKD and SSc with normal renal function. Conclusion. Urinary levels of candidate molecular markers appear to reflect SSc-CKD more than serum markers. MCP1 and ICAM-1 are promising molecular markers for SSc-CKD and might be potential biomarkers of SSc renal involvement. This might be explored in future prospective analyses.

OBJECTIVES:A rising burden from end-stage kidney disease with poor outcomes in the frail, elderly population has seen the emergence of a non-dialytic option, also known as maximum conservative management (MCM). Despite an established MCM programme in our institution, it was anecdotally observed that some MCM patients would end up being dialysed short and long term. We explored treatment modality changes from MCM to renal replacement therapy (RRT), the reasons surrounding the change, and aimed to quantify survival in this cohort of patients.METHODS:44 patients were identified as being MCM, who changed modalities to RRT, from 2000 to 2015, using the Royal Free Hospital Renal Unit's database. Electronic health records were reviewed retrospectively. Associations with 12-month mortality were explored and Kaplan-Meier method used to predict survival.RESULTS:The most common modality change was to haemodialysis (81%), with one transplantation, and rest peritoneal dialysis. 28 patients commenced dialysis as unplanned starters, with the most common symptom being fluid overload. One-year survival was associated with increased age (75 vs 83, p=0.004, for alive vs dead) and had lower mean Charlson Comorbidity Index (6.2 vs 7.3, p=0.021). Median survival of 65 months following RRT initiation was predicted by the Kaplan-Meier method.CONCLUSIONS:Patients changed modalities from MCM to RRT due to symptoms, the most common being fluid overload. Despite an unplanned change to RRT, survival appears to be significant at 65 months in this study, indicating clinicians are continuing to offer RRT to patients appropriately.

Increasing numbers of doctors in training are taking career breaks, with burnout cited as a potential cause. This study analysed General Medical Council (GMC) national training survey data (renal medicine) to understand the impacts of changing workforce demographics on trainee outcomes and wellbeing. Increasing proportions of female, Black, Asian and minority ethnic (BAME), and international medical graduates are entering the workforce. Specialty exam pass rates have fallen and are lower for BAME and international medical graduates in renal medicine. Time to complete higher specialty training has increased for female trainees. Self-reported burnout rates for renal trainees were higher than other medical specialties and highest for male BAME trainees. Burnout was only partially mitigated by less-than-full-time working, but had no impact on progression, sick-leave or time out of training. It is important to recognise changes to the workforce and proactively plan to effectively support a more diverse group of trainees, to enable them to succeed and reduce differential attainment.