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Objectives ANCA-associated vasculitis (AAV) is a rare autoimmune disorder that commonly involves the kidney. Early identification of kidney involvement, assessing treatment-response and predicting outcome are important clinical challenges. Here, we assessed the potential utility of interval kidney biopsy in AAV. Methods In a tertiary referral centre with a dedicated vasculitis service, we identified patients with AAV who had undergone interval kidney biopsy, defined as a repeat kidney biopsy (following an initial biopsy showing active AAV) undertaken to determine the histological response in the kidney following induction immunosuppression. We analysed biochemical, histological and outcome data, including times to kidney failure and death for all patients. Results We identified 57 patients with AAV who underwent at least one interval kidney biopsy (59 interval biopsies in total; median time to interval biopsy ∼130 days). Of the 59 interval biopsies performed, 24 (41%) patients had clinically suspected active disease at time of biopsy which was confirmed histologically in only 42% of cases; 35 (59%) patients were in clinical disease-remission, and this was correct in 97% of cases. The clinician's impression was incorrect in one in four patients. Hematuria at interval biopsy did not correlate with histological activity. Interval biopsy showed fewer acute lesions and more chronic damage compared with initial biopsy and led to immunosuppressive treatment-change in 75% (44/59) of patients. Clinical risk prediction tools tended to operate better using interval biopsy data. Conclusion Interval kidney biopsy is useful for determining treatment-response and subsequent disease management in AAV. It may provide better prognostic information than initial kidney biopsy and should be considered for inclusion into future clinical trials and treatment protocols for patients with AAV. [ABSTRACT FROM AUTHOR]

The majority of patients (8/11) had kidney involvement, with 6 patients undergoing kidney biopsy to confirm this (Figure 1A). Two patients underwent an interval kidney biopsy to confirm histologic disease remission (Figure 1B). Eleven patients with active, organ-threatening AAV were treated without any oral or intravenous glucocorticoids (Table 1); six patients presented with de novo disease and five with relapse. Six patients had granulomatosis with polyangiitis (GPA) and five patients had microscopic polyangiitis. [Extracted from the article]

Objective ANCA-associated vasculitis (AAV) is a small vessel vasculitis that commonly presents in the elderly. However, there are few long-term outcome data for these patients. Here, we assessed long-term outcomes in a single-centre cohort of elderly patients with AAV. Additionally, we tested whether a pre-morbid frailty score could aid prognosis. Methods Using a prospectively-compiled dataset, we investigated patients over the age of 65 who presented with AAV between 2005 and 2017 to a regional vasculitis centre. We used a Cox model to determine the factors associated with mortality. We also compared outcomes in pre-specified subgroups stratified by baseline frailty score, ANCA serotype and induction immunosuppression (with cyclophosphamide, rituximab or mycophenolate mofetil used as the main glucocorticoid-sparing agent). Results 83 patients were included in the study and were followed for a median of 1203 days. Median age was 74 years (range 65–92). Two- and five-year survival in the overall cohort were 83% (95% CI 75, 92%) and 75% (95% CI 65, 86%), respectively. The median cumulative dose of oral prednisolone was 2030 mg during the first three months. Only one patient received intravenous glucocorticoids. Age, frailty score and CRP at presentation were independently associated with mortality; all deaths occurred in patients aged over 75 at presentation. Patients treated with a cyclophosphamide-based induction regimen tended to be younger than those treated with rituximab or mycophenolate mofetil. Survival was better in the cyclophosphamide-treated group. Conclusion In the contemporary era, the overall prognosis of AAV in elderly patients is good. Baseline frailty associates with disease outcomes including mortality. A low-dose glucocorticoid regimen (avoiding intravenous methylprednisolone) can be used to treat AAV effectively in elderly patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Bone fractures are an important cause of morbidity and mortality in patients on renal replacement therapy (RRT). The aim of this multicentre observational study was to quantify the incidence of radiologically proven bone fracture by anatomical site in prevalent RRT groups and study its relationship to potential risk factors. METHODS: We performed a retrospective analysis of electronic records of all 2096 adults prevalent on RRT in the West of Scotland on 7 July 2010 across all hospitals (except one where inception was 1 August 2011) to identify all subsequent radiologically proven fractures during a median 3-year follow-up. RESULTS: There were 340 fractures, with an incidence of 62.8 per 1000 patient-years. The incidences were 37.6, 99.2 and 57.6 per 1000 patient-years in the transplant, haemodialysis (HD) and peritoneal dialysis (PD) groups, respectively (P < 0.05). In the multivariable model, age and HD (relative to transplant or PD) were independently associated with increased risk of fractures, while primary glomerular disease, increasing serum albumin and taking alfacalcidol or lanthanum were associated with decreased risk. In a multivariable model of only HD patients, age was independently associated with an increased risk of fractures, while glomerular disease, high serum albumin and being on alfacalcidol and lanthanum were associated with decreased risk. In a multivariable model in transplant patients, there were no significant independent predictors of fracture. CONCLUSIONS: The risk of symptomatic bone fracture is high in RRT patients and is ~2.5 times higher in HD than in renal transplant patients, with the increased risk being independent of baseline factors. Fracture risk increases with age and lower serum albumin and is reduced if the primary renal diagnosis is glomerular disease. The possible protective role of alfacalcidol and lanthanum in HD patients deserves further exploration. [ABSTRACT FROM AUTHOR]

Vascular and kidney dysfunction commonly co-exist. There is a need for biomarkers of vascular health. Circulating microRNAs are biomarkers; miR-126 is endothelial cell-enriched. We measured circulating miR-126 in rats with nephrotoxic nephritis (NTN) and humans with acute endothelial and renal injury (vasculitis associated with autoantibodies to neutrophil cytoplasm antigens (ANCAs)). We compared these findings to those from patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) and explored the relationship between miR-126 and vascular dysfunction. In NTN, miR-126 was reduced. In ANCA vasculitis (N = 70), pre-treatment miR-126 was reduced compared to health (N = 60) (88-fold). miR-126 increased 3.4-fold post-treatment but remained lower than in health (∼26-fold). Argonaute 2-bound miR-126 increased with ANCA vasculitis treatment. miR-126 did not differ between CKD (N = 30) and health but its concentration correlated with endothelial dysfunction. miR-126 was reduced in ESRD (N = 15) (∼350 fold). miR-126 may be a marker of vascular inflammation and could aid decision-making., Competing Interests: None of the authors have any conflicts of interest., (© 2020 The Author(s).)

Competing Interests: Competing interests The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of The BMJ policy on financial interests are here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests

Background: The management of ischemic nephropathy due to atherosclerotic renal artery stenosis has become increasingly conservative in the modern era, with current guidelines recommending optimized medical therapy as the initial step. The doubts raised by the recently published trials of revascularization strategies have led to a renewed focus on pharmacological strategies promoting blood pressure control and renal protection. It is essential to further elucidate the pathophysiological mechanisms underlying hypoperfusion induced renal microvascular dysfunction with subsequent tissue injury and fibrogenesis. The role of renin angiotensin aldosterone system as a mediator of the main pathophysiological consequences of ischemic nephropathy is well known. However, more recent experimental evidence on the adrenergic system and intrarenal tubular feedback mechanisms has stimulated new interest towards a multi-target therapeutic approach., Methods: This review focuses on the pharmacology of the principle therapeutic drug classes currently used in the treatment of atherosclerotic renal artery stenosis with an analysis of their metabolic aspects and use in clinical practice based on evidence from clinical trials., Results and Conclusions: An optimal pharmacologic approach is crucial for a successful prevention of renal injury and cardiovascular events in this high-risk population. Antihypertensive treatment should include renin angiotensin aldosterone system blockade medication not only for their antihypertensive properties, but especially for those cardio and renoprotective.