Urinary complement proteins are increased in children with IgA vasculitis (Henoch-Schönlein purpura) nephritis

BACKGROUND: Children with immunoglobulin A vasculitis (IgAV Henoch-Schönlein purpura) frequently encounter nephritis (IgAV-N) with 1–2% risk of kidney failure. The pathophysiology of IgAV-N is not fully understood with speculation that complement may contribute. The aim of this study was to identify whether urinary complement proteins are increased in children with IgAV-N. METHODS: A cross-sectional prospective cohort of children with IgAV were recruited together with controls including healthy children and children with systemic lupus erythematosus (SLE). Patients were subdivided according to the presence of nephritis. Urinary C3, C4, C5, and C5a were measured by enzyme-linked immunosorbent assay (ELISA) and corrected for urinary creatinine. RESULTS: The study included 103 children; 47 with IgAV (37 IgAV without nephritis, IgAVwoN; 10 IgAV-N), 30 SLE and 26 healthy children. Urinary complement C3, C4, and C5 were all statistically significantly increased in all children with IgAV compared to SLE patients (all p < 0.05). In patients with IgAV-N, urinary complement C3, C4, C5, C5a were all statistically significantly increased compared to IgAVwoN (C3 14.65 μg/mmol [2.26–20.21] vs. 2.26 μg/mmol [0.15–3.14], p = 0.007; C4 6.52 μg/mmol [1.30–9.72] vs. 1.37 μg/mmol [0.38–2.43], p = 0.04; C5 1.36 μg/mmol [0.65–2.85] vs. 0.38 μg/mmol [0.03–0.72], p = 0.005; C5a 101.9 ng/mmol [15.36–230.0] vs. 18.33 ng/mmol [4.27–33.30], p = 0.01). Using logistic regression, the urinary complement components produced an outstanding ability to discriminate between patients with and without nephritis in IgAV (AUC 0.92, p < 0.001). CONCLUSIONS: Children with IgAV-N have evidence of increased complement proteins present in their urine that may indicate a pathological role and may allow treatment stratification. GRAPHICAL ABSTRACT: [Figure: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00467-022-05747-3.