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Biospectroscopy offers the ability to simultaneously identify key biochemical changes in tissue associated with a given pathological state to facilitate biomarker extraction and automated detection of key lesions. Herein, we evaluated the application of machine learning in conjunction with Raman spectroscopy as an innovative low-cost technique for the automated computational detection of disease activity in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis (AAGN). Consecutive patients with active AAGN and those in disease remission were recruited from a single UK centre. In those with active disease, renal biopsy samples were collected together with a paired urine sample. Urine samples were collected immediately prior to biopsy. Amongst those in remission at the time of recruitment, archived renal tissue samples representative of biopsies taken during an active disease period were obtained. In total, twenty-eight tissue samples were included in the analysis. Following supervised classification according to recorded histological data, spectral data from unstained tissue samples were able to discriminate disease activity with a high degree of accuracy on blind predictive modelling: F-score 95% for >25% interstitial fibrosis and tubular atrophy (sensitivity 100%, specificity 90%, area under ROC 0.98), 100% for necrotising glomerular lesions (sensitivity 100%, specificity 100%, area under ROC 1) and 100% for interstitial infiltrate (sensitivity 100%, specificity 100%, area under ROC 0.97). Corresponding spectrochemical changes in paired urine samples were limited. Future larger study is required, inclusive of assigned variables according to novel non-invasive biomarkers as well as the application of forward feature extraction algorithms to predict clinical outcomes based on spectral features. [ABSTRACT FROM AUTHOR]

Background: Frailty is associated with adverse health outcomes in people with chronic kidney disease (CKD). Evidence supporting targeted interventions is needed. This pilot randomised controlled trial (RCT) aimed to inform the design of a definitive RCT evaluating the effectiveness of a home-based exercise intervention for pre-frail and frail older adults with CKD. Methods: Participants were recruited from nephrology outpatient clinics to this two-arm parallel group mixed-methods pilot RCT. Inclusion criteria were: ≥65 years old; CKD G3b-5; and Clinical Frailty Scale score ≥4. Participants categorised as pre-frail or frail using the Frailty Phenotype were randomised to a 12-week progressive multi-component home-based exercise programme or usual care. Primary outcome measures included eligibility, recruitment, adherence, outcome measure completion and participant attrition rate. Semi-structured interviews were conducted with participants to explore trial and intervention acceptability. Results: Six hundred and sixty-five patients had an eligibility assessment with 217 (33%; 95% CI 29, 36) eligible. Thirty-five (16%; 95% CI 12, 22) participants were recruited. Six were categorised as robust and withdrawn prior to randomisation. Fifteen participants were randomised to exercise and 14 to usual care. Eleven (73%; 95% CI 45, 91) participants completed ≥2 exercise sessions/week. Retained participants completed all outcome measures (n = 21; 100%; 95% CI 81, 100). Eight (28%; 95% CI 13, 47) participants were withdrawn. Fifteen participated in interviews. Decision to participate/withdraw was influenced by perceived risk of exercise worsening symptoms. Participant perceived benefits included improved fitness, balance, strength, well-being, energy levels and confidence. Conclusions: This pilot RCT demonstrates that progression to definitive RCT is possible provided recruitment and retention challenges are addressed. It has also provided preliminary evidence that home-based exercise may be beneficial for people living with frailty and CKD. Trial registration: ISRCTN87708989; https://clinicaltrials.gov/. [ABSTRACT FROM AUTHOR]

Identifying persistent or relapsing disease in anti‐neutrophil cytoplasmic autoantibody‐ associated vasculitis (AAV) remains a clinical challenge with an unmet need for a reliable biomarker of multisystem disease. In this study, we confirm for the first time that Raman spectroscopy offers a novel cost‐effective candidate biomarker to discriminate active disease from remission in AAV with excellent accuracy. Spectrochemical interrogation of plasma and serum samples demonstrated equal ability to discriminate disease activity with good group separation on PC1 direction and a high degree of accuracy on validation testing using blind predictive modelling: F‐score 80% for plasma (specificity 93.3%, sensitivity 70%, AUC 0.95) and 80% for serum (specificity 80%, sensitivity 80%, AUC 0.92). Similar findings were seen on analysis of paired remission samples following successful remission‐induction therapy. A larger study with longitudinal data is required to validate these findings with the potential to aid patient care. [ABSTRACT FROM AUTHOR]

Introduction Frailty is highly prevalent in adults with chronic kidney disease (CKD) and is associated with adverse health outcomes including falls, poorer health-related quality of life (HRQOL), hospitalisation and mortality. Low physical activity and muscle wasting are important contributors to physical frailty in adults with CKD. Exercise training may improve physical function and frailty status leading to associated improvements in health outcomes, including HRQOL. The EX-FRAIL CKD trial aims to inform the design of a definitive randomised controlled trial (RCT) that investigates the effectiveness of a progressive, multicomponent home-based exercise programme in prefrail and frail older adults with CKD. Methods and analysis The EX-FRAIL CKD trial is a two-arm parallel group pilot RCT. Participants categorised as prefrail or frail, following Frailty Phenotype (FP) assessment, will be randomised to receive exercise or usual care. Participants randomised to the intervention arm will receive a tailored 12-week exercise programme, which includes weekly telephone calls to advise on exercise progression. Primary feasibility outcome measures include rate of recruitment, intervention adherence, outcome measure completion and participant attrition. Semistructured interviews with a purposively selected group of participants will inform the feasibility of the randomisation procedures, outcome measures and intervention. Secondary outcome measures include physical function (walking speed and Short Physical Performance Battery), frailty status (FP), fall concern (Falls Efficacy Scale-International tool), activities of daily living (Barthel Index), symptom burden (Palliative care Outcome Scale-Symptoms RENAL) and HRQOL (Short Form-12v2). Ethics and dissemination Ethical approval was granted by a National Health Service (NHS) Regional Ethics Committee and the NHS Health Research Authority. The study team aims to publish findings in a peer-reviewed journal and presents the results at relevant national and international conferences. A summary of findings will be provided to participants, a local kidney patient charity and the funding body. [ABSTRACT FROM AUTHOR]

Background Understanding how frailty affects health-related quality of life (HRQOL) in those with chronic kidney disease (CKD) could assist in the development of management strategies to improve outcomes for this vulnerable patient group. This study aimed to evaluate the relationship between frailty and HRQOL in patients with CKD Stages 4 and 5 (G4–5) and those established on haemodialysis (G5D). Methods Ninety participants with dialysis-dependent chronic kidney disease (CKD G4–5D) were recruited between December 2016 and December 2017. Frailty was assessed using the Frailty Phenotype, which included assessments of unintentional weight loss, weakness (handgrip strength), slowness (walking speed), physical activity and self-perceived exhaustion. HRQOL was assessed using the RAND 36-Item Health Survey Version 1.0 (SF-36). Results Nineteen (21%) patients were categorized as frail. Frailty, when adjusted for age, gender, dialysis dependence and comorbidity, had a significant effect on five of the eight SF-36 domains: physical functioning, role limitations due to emotional problems, energy/fatigue, social functioning and pain. Regression modelling best explained the variation in the physical functioning domain (adj. R 2 = 0.27, P < 0.001), with frailty leading to a 26-point lower score. Exhaustion was the only Frailty Phenotype component that had a significant effect on scores across all SF-36 domains. Conclusions Frailty is independently associated with worse HRQOL in patients with CKD G4–5D, with self-perceived exhaustion being the most significant Frailty Phenotype component contributing to HRQOL. Efforts should be made to identify frail patients with CKD so that management strategies can be offered that aim to improve morbidity, mortality and patient-reported outcomes, including HRQOL and fatigue. [ABSTRACT FROM AUTHOR]

Background: Understanding how frailty affects health-related quality of life (HRQOL) in those with chronic kidney disease (CKD) could assist in the development of management strategies to improve outcomes for this vulnerable patient group. This study aimed to evaluate the relationship between frailty and HRQOL in patients with CKD Stages 4 and 5 (G4–5) and those established on haemodialysis (G5D)., Methods: Ninety participants with chronic kidney disease (CKD G4–5D) were recruited between December 2016 and December 2017. Frailty was assessed using the Frailty Phenotype, which included assessments of unintentional weight loss, weakness (handgrip strength), slowness (walking speed), physical activity and self-perceived exhaustion. HRQOL was assessed using the RAND 36-Item Health Survey Version 1.0 (SF-36)., Results: Nineteen (21%) patients were categorized as frail. Frailty, when adjusted for age, gender, dialysis dependence and comorbidity, had a significant effect on five of the eight SF-36 domains: physical functioning, role limitations due to emotional problems, energy/fatigue, social functioning and pain. Regression modelling best explained the variation in the physical functioning domain (adj. R2 = 0.27, P < 0.001), with frailty leading to a 26-point lower score. Exhaustion was the only Frailty Phenotype component that had a significant effect on scores across all SF-36 domains., Conclusions: Frailty is independently associated with worse HRQOL in patients with CKD G4–5D, with self-perceived exhaustion being the most significant Frailty Phenotype component contributing to HRQOL. Efforts should be made to identify frail patients with CKD so that management strategies can be offered that aim to improve morbidity, mortality and patient-reported outcomes, including HRQOL and fatigue., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)