Comparison of Complement Pathway Activation in Autoimmune Glomerulonephritis

Can Urinary Complement Proteins Stratify Patients to Therapeutic Complement Inhibitors?

“…This motivates the research presented by Genest et al. 8 in this issue of the KI Reports . The paper presents comparative urinary complement protein levels from patients with 5 autoimmune kidney diseases.…”

“…The proteins detected by Genest et al. 8 are outlined and colored red and are involved in activity of each complement pathway. …”

“…With the aim of identifying the pathogenically dominant pathway in each GN, the authors attempted to select points of maximal and minimum clinical activity with proteinuria, at which point urinary markers were measured. 8 The analyzed proteins represented the alternative, lectin, classical, and terminal complement pathways ( Figure 1 ).…”

“…Urinary levels of terminal pathway proteins were highest in focal segmental glomerulosclerosis and membranous nephropathy, even after correcting for differences in proteinuria. 8 Furthermore, markers of C3 convertase (C3a) and classical complement pathway (C1q) activity were lowest in lupus nephritis. Urinary sC5b-9, a terminal pathway marker, was similar to a control cohort of patients with diabetic nephropathy.…”

“…Urinary sC5b-9, a terminal pathway marker, was similar to a control cohort of patients with diabetic nephropathy. 8 Given these findings, it is important to highlight limitations to the research methods. First, the study was observational.…”