The Limitations of Frailty Assessment Tools in ANCA-Associated Vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) can be associated with a high burden of morbidity and mortality in an ageing population. It is increasingly recognised that individualised management is needed. Few studies have looked specifically at frailty related outcomes in AAV and a gap remains in understanding the application of frailty assessment tools in these patients. We carried out a single centre, cohort study between 2017 to 2022. Forty-one patients who had newly diagnosed or relapsing AAV and aged ≥65 years were included. The Clinical Frailty Scale (CFS) score at presentation was assessed by health care practitioners and interval CFS scores were carried out a minimum of 6 weeks from diagnosis. The aim was to determine if patients living with frailty had worse outcomes or if their perceived frailty improved with immunosuppressive treatment. The median CFS at diagnosis was 4 (vulnerable) and this remained at follow up. There was no significant interval change in CFS (P=0.16) suggesting that the patients did not become frailer and instead there was a tendency towards improved frailty scores at re-assessment. There was no significant difference in end stage kidney disease between those with higher (>5) or lower (≤5) CFS (P=1.0), although crude mortality was higher among those with an initial CFS >5 (P=0.03). Overall, we demonstrated that CFS has limitations in determining patients that may be frail as a result of disease burden with the potential to improve with treatment and clinicians should be mindful of this when making decisions relating to management.

Symptom-burden in people living with frailty and chronic kidney disease.

BACKGROUND: Frailty is independently associated with worse health-related quality of life (HRQOL) in chronic kidney disease (CKD). However, the relationship between frailty and symptom experience is not well described in people living with CKD. This study's aim was to evaluate the relationship between frailty and symptom-burden in CKD. METHODS: This study is a secondary analysis of a cross-sectional observational study, the QCKD study (ISRCTN87066351), in which participants completed physical activity, cardiopulmonary fitness, symptom-burden and HRQOL questionnaires. A modified version of the Frailty Phenotype, comprising 3 self-report components, was created to assess frailty status. Multiple linear regression was performed to assess the association between symptom-burden/HRQOL and frailty. Logistic regression was performed to assess the association between experiencing symptoms frequently and frailty. Principal Component Analysis was used to assess the experienced symptom clusters. RESULTS: A total of 353 patients with CKD were recruited with 225 (64%) participants categorised as frail. Frail participants reported more symptoms, had higher symptom scores and worse HRQOL scores. Frailty was independently associated with higher total symptom score and lower HRQOL scores. Frailty was also independently associated with higher odds of frequently experiencing 9 out of 12 reported symptoms. Finally, frail participants experienced an additional symptom cluster that included loss of appetite, tiredness, feeling cold and poor concentration. CONCLUSIONS: Frailty is independently associated with high symptom-burden and poor HRQOL in CKD. Moreover, people living with frailty and CKD have a distinctive symptom experience. Proactive interventions are needed that can effectively identify and address problematic symptoms to mitigate their impact on HRQOL.

ANCA-associated vasculitis: pathogenesis, novel markers of the disease and emerging therapies.

Much has been learned in recent years on the pathogenesis of ANCA-associated small-vessel vasculitis. The interaction of primed neutrophils with ANCA and endothelial cells is crucial to the disease. Next we gained a better understanding, from animal models, of the pathogenetic importance of the ANCA antibody. Very recent evidence provides intriguing data regarding the link between infection and vasculitis, LAMP-2 antibodies as novel markers, and NETs as a novel pathogenetic mechanism. It remains to be seen whether others are able to corroborate these findings and whether testing for LAMP-2 antibodies will become part of the clinical routine in vasculitis. Recent years also saw the emergence of various new markers of endothelial damage and the disease itself, such as circulating endothelial cells and endothelial microparticles. These novel markers correlate well with disease activity; they may well complement traditional diagnostic tools, such as ANCA testing. Preliminary evidence has provided some insight into the balance between endothelial damage and repair. Exciting preliminary data also indicate that circulating endothelial cells may not only be markers of disease activity but that these cells may have pathogenetic importance in their own right. These findings may have profound implications for the pathogenesis of vasculitis and vascular disease in general. Recent years also saw the publication of a number of seminal studies for the treatment of ANCA-associated vasculitis. We now have a much better understanding of the role of pulse intravenous cyclophosphamide and plasma exchange than ten or even five years ago. Further studies must now show whether plasma exchange is also beneficial for less severely ill patients with AASV. Finally, as ever, it is hoped that further progress in understanding the disease pathogenesis will also provide more tailored and less toxic therapies.