Abstract

Aims: The membrane attack complex (MAC) plays a key role in the pathogenesis of experimental membranous nephropathy. However, the clinical significance of urinary MAC (UMAC) excretion in human idiopathic membranous nephropathy (IMGN) and other proteinuric glomerulopathies is not fully elucidated. Patients and methods: We studied 16 patients with IMGN and 4 with focal segmental glomerulosclerosis (FSGS) who participated in clinical trials. Serial measures of UMAC, proteinuria and serum indices of renal function were conducted over the 26 weeks of treatment. Patients with UMAC excretion at treatment outset were identified as UMAC (+). We compared UMAC (+) and UMAC (?) patients with respect to several parameters at treatment initiation and study completion including age, disease duration, serum creatinine, creatinine clearance and proteinuria. In the UMAC(+) group we compared changes in UMAC values over time with patient outcome. Results: There were no demographic or clinical characteristics at presentation and study completion that distinguished the 8 UMAC (+) patients from the 12 UMAC (?) patients. As well, UMAC positivity did not predict response to therapy. Among the 8 UMAC (+) patients, 4 (3 IMGN and 1 FSGS) responded to therapy and in all cases, UMAC became undetectable. Non-responders to therapy (2 IMGN and 2 FSGS) continued to excrete UMAC at the conclusion of treatment. Initial UMAC levels of responders and non-responders were similar. Conclusions: UMAC levels parallel proteinuria not only in IMGN but also in FSGS patients. Immunomodulation may reduce glomerular formation of MAC in IMGN. In both histologic subtypes, the reduction in filtered protein may diminish the activation of MAC at the tubulointerstitial interface. However, the clinical utility of measuring UMAC is limited by its low prevalence, the absence of histopathologic specificity and its equivocal role in predicting outcome.

Author Details

Authors

• D.C. Cattran
• R. Wald
• P.E.C. Brenchley
• B. Coupes for the North American Nephrotic Syndrome Group
• the Genes
• Gender
• Glomerulonephritis Group

Departments

• ¹ Department of Medicine, Toronto General Hospital/University Health Network and University of Toronto, Canada and
• ² Renal Research, Manchester Institute of Nephrology and Transplantation, Manchester Royal Infirmary, Oxford Head, Manchester, UK

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