Clinical Investigation

Kidney International (1991) 40, 533–538; doi:10.1038/ki.1991.242

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

Matthias Schulze, James V Donadio Jr, Charles J Pruchno, Patricia J Baker, Richard J Johnson, Rolf A K Stahl, Sandra Watkins, Donald C Martin, Reinhard Wurzner, Otto Gotze and William G Couser

Department of Medicine, Division of Nephrology, University of Washington, Seattle, Washington; the Division of Nephrology and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota; Department of Medicine of the Johann Wolfgang Goethe-University, Frankfurt, Germany; Division of Pediatric Nephrology, Children's Hospital Medical Center, Seattle, Washington; Department of Biostatistics, University of Washington, Seattle, Washington, USA; and Department of Immunology, University of Gottingen, Gottingen, Germany

Correspondence: Dr William G Couser, Division of Nephrology RM 11, Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195, USA.

Received 1 February 1991; Revised 29 April 1991; Accepted 1 May 1991.

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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.

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