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Summary 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., Graphical abstract, Highlights • New biomarkers are needed that report vascular function in patients with kidney disease • The endothelial microRNA, miR-126, was reduced with vascular inflammation (vasculitis) • miR-126 correlated with vascular health in chronic kidney disease • Circulating miR-126 may be a marker of vascular dysfunction, Molecular Physiology; Molecular Genetics; Molecular Biology; Immunology

SummaryBackgroundParacetamol poisoning is common worldwide. It is treated with intravenous acetylcysteine, but the standard regimen is complex and associated with frequent adverse effects related to concentration, which can cause treatment interruption. We aimed to ascertain whether adverse effects could be reduced with either a shorter modified acetylcysteine schedule, antiemetic pretreatment, or both.MethodsWe undertook a double-blind, randomised factorial study at three UK hospitals, between Sept 6, 2010, and Dec 31, 2012. We randomly allocated patients with acute paracetamol overdose to either the standard intravenous acetylcysteine regimen (duration 20·25 h) or a shorter (12 h) modified protocol, with or without intravenous ondansetron pretreatment (4 mg). Masking was achieved by infusion of 5% dextrose (during acetylcysteine delivery) or saline (for antiemetic pretreatment). Randomisation was done via the internet and included a minimisation procedure by prognostic factors. The primary outcome was absence of vomiting, retching, or need for rescue antiemetic treatment at 2 h. Prespecified secondary outcomes included a greater than 50% increase in alanine aminotransferase activity over the admission value. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov (identifier NCT01050270).FindingsOf 222 patients who underwent randomisation, 217 were assessable 2 h after the start of acetylcysteine treatment. Vomiting, retching, or need for rescue antiemetic treatment at 2 h was reported in 39 of 108 patients assigned to the shorter modified protocol compared with 71 of 109 allocated to the standard acetylcysteine regimen (adjusted odds ratio 0·26, 97·5% CI 0·13–0·52; p