Elevated urinary excretion of the C5b-9 complex in membranous nephropathy

Abstract

Elevated urinary excretion of the C5b-9 complex in membranous nephropathy. In experimental membranous nephropathy, antibody binding to glomerular epithelial cell membrane antigens results in complement activation and formation of complement C5b-9 membrane attack complexes in glomeruli. During active disease, the C5b-9 complexes are shed into the urine. To test the hypothesis that a similar mechanism might be operative in human membranous nephropathy, we measured urinary excretion of C5b-9 and C5 in 146 proteinuric patients with biopsy-proven glomerular diseases or diabetes mellitus. Urinary excretion of C5b-9 relative to C5 excretion was higher in 40 patients with membranous nephropathy than in 106 patients with proteinuria due to non-membranous glomerulonephritis when analyzed by covariance analysis (P < 0.0002). Urinary C5b-9 excretion was higher in membranous nephropathy than in membranoproliferative glomerulonephritis (N = 13, P < 0.05), minimal change-focal sclerosis (N = 33, P < 0.001), mesangial proliferative glomerulonephritis (N = 9, P < 0.02) and IgA nephropathy (N = 7, P < 0.025). Urinary C5b-9 excretion was also higher in patients with lupus nephritis (N = 18, P < 0.02) compared to those with non-membranous glomerulonephritis. The lupus patients with the highest excretion had clinical or pathological features of membranous nephropathy. Nine patients with membranous nephropathy and elevated urinary C5b-9 excretion had a shorter duration of disease (P < 0.05), lower serum creatinine levels (P < 0.05) and more proteinuria (P < 0.02) than the 31 membranous nephropathy patients with normal values. The finding of increased urinary C5b-9 excretion in a subset of patients with idiopathic or lupus membranous nephropathy suggests an autoimmune basis for glomerular disease in these patients, and may indicate that these patients have ongoing immune deposit formation.