Circulating argonaute-bound microRNA-126 reports vascular dysfunction & response to treatment in acute & chronic kidney disease

Background Vascular and kidney dysfunction commonly co-exist. There is an unmet need for biomarkers of vascular health. Circulating microRNAs (miRs) are disease 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 (ANCA)). We then 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 markers of vascular dysfunction. Methods In rats, NTN was induced with nephrotoxic serum. Samples were prospectively collected from 70 patients with ANCA vasculitis (at presentation and once in treatment-induced remission), healthy subjects (n=60), patients with CKD (n=30) and ESRD before and after dialysis (n=15). In humans and rats, miR-126 and miR-122 (liver-specific control) were measured and correlated with vascular function. Results In NTN rats, miR-126 was selectively reduced. In ANCA vasculitis, pre-treatment circulating miR-126 was reduced compared to health (88-fold reduction, ROC-AUC 0.87 (0.80-0.94)). miR-126 increased 3.4-fold post-treatment but remained lower than in health (∼26-fold). There was no change in miR-122. Plasma fractionation demonstrated that argonaute 2-bound miR-126 increased with treatment of ANCA vasculitis. Urinary miR-126 decreased post-treatment. miR-126 did not differ between CKD and health but its concentration significantly correlated with measures of endothelial dysfunction. miR-126 was substantially reduced in ESRD (∼350 fold compared to health and CKD). Conclusions miR-126 may be a marker of vascular inflammation and has the potential to aid in clinical decision-making.