Membranous nephropathy: not just a disease for adults

Abstract

Membranous nephropathy (MN) is an immune complex-mediated cause of the nephrotic syndrome that can occur in all age groups, from infants to the elderly. While systemic disorders such as hepatitis B infection or lupus may more frequently cause secondary MN in the younger population, primary or "idiopathic" MN has generally been considered a disease of adults. Recent progress in our understanding of primary disease was recently made when the target antigen in primary MN was identified as the M-type phospholipase A2 receptor (PLA2R). Circulating anti-PLA2R antibodies may serve both as a diagnostic tool for distinguishing primary from secondary disease and as a biomarker for monitoring the immunologic activity of this organ-specific autoimmune disease during treatment. Whereas definitive therapy for secondary forms of MN should be targeted at the underlying cause, immunosuppressive therapy is often necessary for primary disease. Alkylating agents in combination with corticosteroids, as well as calcineurin inhibitors (± steroids), are first line agents due to randomized controlled trials in an adult population with relatively long durations of follow-up. However, rituximab, mycophenolate and adrenocorticotropic hormone have shown promise in smaller and/or observational studies. The optimal therapy for children and adolescents with MN is less well defined.

Figure 1

Immunofluorescence staining for PLA₂R in kidney biopsy specimens from an 11 year-old male (A) and a 74 year-old male (B) with membranous nephropathy. Note the absence of granular staining in panel A which is indicative of non-PLA₂R-associated MN. The finding of granular PLA₂R staining in a capillary loop pattern (B) is indicative of primary PLA₂R-associated membranous nephropathy. Images by R. Ayalon, 400x.