Are urinary levels of high mobility group box 1 markers of active nephritis in anti‐neutrophil cytoplasmic antibody‐associated vasculitis?

Summary The objective of this study is to evaluate urinary high mobility group box 1 ( HMGB 1) levels as markers for active nephritis in patients with anti‐neutrophil cytoplasmic antibody (ANCA) ‐associated vasculitis ( AAV ) in comparison with urinary CD 4 + effector memory T cells and urinary monocyte chemoattractant protein‐1 ( MCP ‐1). Twenty‐four AAV patients with active nephritis and 12 healthy controls ( HC ) were evaluated. In nine patients, samples were also obtained during remission. Urinary levels of HMGB 1 were measured by W estern blot. CD 4 + T cells and CD 4 + effector memory T cells ( CD 4 + CD 45 RO + CCR 7 ‐ ) were determined in urine and whole blood by flow cytometry. Measurement of urinary levels of MCP ‐1 and serum HMGB 1 levels were performed by enzyme‐linked immunosorbent assay ( ELISA ). AAV patients with active nephritis had higher median intensity of HMGB 1 in urine than HC [10·3 (7·05–18·50) versus 5·8 (4·48–7·01); P  = 0·004]. Both urinary HMGB 1 and MCP ‐1 levels decreased significantly from active nephritis to remission. The urinary MCP ‐1/creatinine ratio correlated with B irmingham V asculitis A ctivity S core ( BVAS ) ( P  = 0·042). No correlation was found between the HMGB 1/creatinine ratio and 24‐h proteinuria, estimated glomerular filtration rate (eGFR) , MCP ‐1/creatinine ratio, BVAS and serum HMGB 1. A positive correlation was found between urinary HMGB 1/creatinine ratio and CD 4 + T cells/creatinine ratio ( P  = 0·028) and effector memory T cells/creatinine ratio ( P  = 0·039) in urine. Urinary HMGB 1 levels are increased in AAV patients with active nephritis when compared with HC and patients in remission, and urinary HMGB 1 levels are associated with CD 4 + T cells and CD 4 + effector memory T cells in urine. Measurement of urinary HMGB 1 may be of additional value in identifying active glomerulonephritis in AAV patients.