Frailty in patients on dialysis.

Frailty is a condition that is frequently observed among patients undergoing dialysis. Frailty is characterized by a decline in both physiological state and cognitive state, leading to a combination of symptoms, such as weight loss, exhaustion, low physical activity level, weakness, and slow walking speed. Frail patients not only experience a poor quality of life, but also are at 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, frailty has no cure. 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 chronic kidney disease-related complications, reducing polypharmacy by deprescription, personalizing 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.

Effect of ethnicity and socioeconomic deprivation on uptake of renal supportive care and dialysis decision-making in older adults.

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.

Medical students as health workers during the COVID-19 pandemic.

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.

Cocaine-induced granulomatosis with polyangiitis-an under-recognized condition.

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.

Zibotentan in systemic sclerosis-associated chronic kidney disease: a phase II randomised placebo-controlled trial.

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.

Frailty score before admission as risk factor for mortality of renal patients during the first wave of the COVID pandemic in London.

Background: Frailty is a known predictor of mortality and poor outcomes during hospital admission. In this large renal retrospective cohort study, we investigated whether frailer COVID-19 positive renal patients had worse outcomes. Design: All SARS-Cov-2 positive renal patients aged ≥18 years who presented to the emergency department at the Royal Free Hospital or at the satellite dialysis centres from 10th of March until the 10th of May 2020, with recent data on frailty, were included. The follow up was until 26th of May 2020. Age, gender, ethnicity, body mass index, chronic kidney disease stage, modality of renal replacement therapy, co-morbidities, Rockwood clinical frailty score (CFS), C reactive protein and the neutrophil-to-lymphocyte count were collected at presentation. The primary outcome was the overall mortality rate following COVID-19 diagnosis. Secondary outcomes included the need for hospital admission. Results: A total of 200 renal patients were SARS-Cov-2 positive. In the 174 patients who had a CFS recorded, the age was 65.4 years ± 15.8 (mean ± SD) and 57,5% were male. At the end of follow up, 26% had died. Frail patients (CFS 5-7) were more than three times more likely to die compared to less frail patients (CFS of 1-4) (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.0-10.6). 118 patients (68%) required admission, but there was no difference in hospital admission rates for frail vs non-frail patients (OR 0.6, CI 0.3-1.7). Conclusions: Frailty is a better predictor of mortality than age and co-morbidities in COVID-19 positive renal patients.

End-stage kidney disease on dialysis: an observational study of modality change from maximum conservative management.

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.

Exploring molecular pathology of chronic kidney disease in systemic sclerosis by analysis of urinary and serum proteins.

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-α, 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-α, 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.

Impact of changing medical workforce demographics in renal medicine over 7 years: Analysis of GMC national trainee survey data.

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.

The Prepare for Kidney Care Study: prepare for renal dialysis versus responsive management in advanced chronic kidney 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.

Rapid implementation of Microsoft Teams in response to COVID-19: one acute healthcare organisation's experience.

Background COVID-19 presented significant challenges to healthcare organisations, which needed to rapidly remodel their services but were unable to allow staff to meet face to face to minimise infection risk. During this communication predicament, National Health Service (NHS) Digital announced the provision of Microsoft Teams, a digital communication and collaboration tool, which was implemented at Royal Free London NHS Foundation Trust within 2 weeks.Method Given the need to deploy at scale, rapidly and with minimal resource, an agile decentralised innovation management approach was used, empowering staff to be local implementors.Results Resulting use cases were highly original and varied, ranging from a COVID-19 Education Programme to coordination of oxygen demand. Analytics showed rapid and persistent adoption, surpassing 500 daily active users within 11 days. Usage continues to increase, consistent with a direct network effect.Conclusion These findings suggest a high demand for this format of communication and high willingness to adopt it. Further qualitative research into staff perceptions would be valuable to confirm this, and to assess the user experience.Overall, this has been a radical approach to digital implementation in healthcare, and has so far proved effective in delivering a cost minimal, rapid communication tool at scale in the midst of a global pandemic.

Keep calm and carry on learning: using Microsoft Teams to deliver a medical education programme during the COVID-19 pandemic.

The outbreak of COVID-19 in the UK in March 2020 required a radical remodelling of the medical workforce at Royal Free London NHS Foundation Trust to prepare for the anticipated surge of hospital admissions. The provision of relevant teaching and training was immediately identified as a priority, particularly for staff due to work outside their regular medical specialty. Rather than deliver face-to-face teaching, doctors at the Trust utilised Microsoft Teams, an online communications and collaboration platform, to deliver a multi-disciplinary Trust-wide education programme responsive to the needs of surveyed medical staff. To date members of 18 departments across the Trust have delivered 51 virtual teaching sessions which have been viewed 3,814 times. During this pandemic the virtual education programme has facilitated rapid dissemination of new information and provided a platform for discussion and unity amongst colleagues with overwhelmingly positive feedback from both learners and teachers.

Quality of life among caregivers of people with end-stage kidney disease managed with dialysis or comprehensive conservative care.

BACKGROUND: To measure health-related and care-related quality of life among informal caregivers of older people with end-stage kidney disease (ESKD), and to determine the association between caregiver quality of life and care recipient's treatment type. METHODS: A prospective cross-sectional study was conducted. Three renal units in the UK and Australia were included. Informal caregivers of people aged ≥75 years with ESKD managed with dialysis or comprehensive conservative non-dialytic care (estimated glomerular filtration (eGFR) ≤10 mL/min/1.73m2) participated. Health-related quality of life (HRQoL) was assessed using Short-Form six dimensions (SF-6D, 0-1 scale) and care-related quality of life was assessed using the Carer Experience Scale (CES, 0-100 scale). Linear regression assessed associations between care-recipient treatment type, caregiver characteristics and the SF-6D utility index and CES scores. RESULTS: Of 63 caregivers, 49 (78%) were from Australia, 26 (41%) cared for an older person managed with dialysis, and 37 (59%) cared for an older person managed with comprehensive conservative care. Overall, 73% were females, and the median age of the entire cohort was 76 years [IQR 68-81]. When adjusted for caregiver sociodemographic characteristics, caregivers reported significantly worse carer experience (CES score 15.73, 95% CI 5.78 to 25.68) for those managing an older person on dialysis compared with conservative care. However, no significant difference observed for carer HRQoL (SF-6D utility index - 0.08, 95% CI - 0.18 to 0.01) for those managing an older person on dialysis compared with conservative care. CONCLUSIONS: Our data suggest informal caregivers of older people on dialysis have significantly worse care-related quality of life (and therefore greater need for support) than those managed with comprehensive conservative care. It is important to consider the impact on caregivers' quality of life when considering treatment choices for their care recipients.

Analysis of Anti-RNA Polymerase III Antibody-positive Systemic Sclerosis and Altered GPATCH2L and CTNND2 Expression in Scleroderma Renal Crisis.

OBJECTIVE: Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) strongly associated with anti-RNA polymerase III antibody (ARA) autoantibodies. We investigated genetic susceptibility and altered protein expression in renal biopsy specimens in ARA-positive patients with SRC. METHODS: ARA-positive patients (n = 99) with at least 5 years' follow-up (49% with a history of SRC) were selected from a well characterized SSc cohort (n = 2254). Cases were genotyped using the Illumina Human Omni-express chip. Based on initial regression analysis, 9 single-nucleotide polymorphisms (SNP) were chosen for validation in a separate cohort of 256 ARA-positive patients (40 with SRC). Immunostaining of tissue sections from SRC or control kidney was used to quantify expression of candidate proteins based upon genetic analysis of the discovery cohort. RESULTS: Analysis of 641,489 SNP suggested association of POU2F1 (rs2093658; P = 1.98 × 10-5), CTNND2 (rs1859082; P = 5.58 × 10-5), HECW2 (rs16849716; P = 1.2 × 10-4), and GPATCH2L (rs935332; P = 4.92 × 10-5) with SRC. Further, the validation cohort showed an association between rs935332 within the GPATCH2L region, with SRC (P = 0.025). Immunostaining of renal biopsy sections showed increased tubular expression of GPATCH2L (P = 0.026) and glomerular expression of CTNND2 (P = 0.026) in SRC samples (n = 8) compared with normal human kidney controls (n = 8), despite absence of any genetic replication for the associated SNP. CONCLUSION: Increased expression of 2 candidate proteins, GPATCH2L and CTNND2, in SRC compared with control kidney suggests a potential role in pathogenesis of SRC. For GPATCH2L, this may reflect genetic susceptibility in ARA-positive patients with SSc based upon 2 independent cohorts.

Health-related quality of life and well-being in people over 75 years of age with end-stage kidney disease managed with dialysis or comprehensive conservative care: a cross-sectional study in the UK and Australia.

OBJECTIVE: To measure health-related quality of life (HRQoL) and well-being in older people with end-stage kidney disease (ESKD) and to determine the association between treatment type and sociodemographic characteristics on these outcome measures. In addition, to assess the convergent validity between the HRQoL and well-being measure and their feasibility and acceptability in this population. DESIGN: Prospective cross-sectional study. SETTING: Three renal units in the UK and Australia. PARTICIPANTS: 129 patients with ESKD managed with dialysis or with an estimated glomerular filtration ≤10 mL/min/1.73 m2 and managed with comprehensive conservative, non-dialytic care. OUTCOME MEASURES: HRQoL and well-being were assessed using Short-Form six dimensions (SF-6D, 0-1 scale); Kidney Disease Quality of Life (KDQOL-36) (0-100 scale) and Investigating Choice Experiments Capability Measure-Older people (ICECAP-O, 0-1 scale). Linear regression assessed associations between treatment, HRQoL and well-being. Pearson's correlation coefficient assessed convergent validity between instruments. RESULTS: Median age of 81 years (IQR 78-85), 65% males; 83 (64%) were managed with dialysis and 46 (36%) with conservative care. When adjusted for treatment type and sociodemographic variables, those managed on dialysis reported lower mean SF-6D utility (-0.05, 95% CI -0.12 to 0.01); lower KDQOL Physical Component Summary score (-3.17, 95% CI -7.61 to 1.27); lower Mental Component Summary score (-2.41, 95% CI -7.66 to 2.84); lower quality of life due to burden (-28.59, 95% CI -41.77 to -15.42); symptoms (-5.93, 95% CI -14.61 to 2.73) and effects of kidney disease (-16.49, 95% CI -25.98 to -6.99) and lower overall ICECAP-O well-being (-0.07, 95% CI -0.16 to 0.02) than those managed conservatively. Correlation between ICECAP-O well-being and SF-6D utility scores was strong overall, 0.65 (p<0.001), but weak to moderate at domain level. CONCLUSIONS: Older people on dialysis report significantly higher burden and effects of kidney disease than those on conservative care. Lower HRQoL and well-being may be associated with dialysis treatment and should inform shared decision-making about treatment options. TRIAL REGISTRATION NUMBER: UK (IRAS project ID: 134360andREC reference 14/LO/0291) and Australia (R20140203 HREC/14/RAH/36).