Membranous nephropathy: The start of a paradigm shift

Purpose of review: Primary membranous nephropathy is a common glomerular disease characterized by sub-epithelial immune deposits that has become the prototype of an autoimmune glomerular disease. The purpose of this review is to highlight recent advances regarding the pathogenesis of membranous nephropathy as well as potential new therapies. Recent findings: The discovery of two major podocyte antigens, neutral endopeptidase (NEP), involved in rare cases of neonatal membranous nephropathy, and the M-type phospholipase A ₂ receptor 1 (PLA ₂R1), the first antigen discovered in adults, have been major 'breakthroughs' in our understanding of the pathogenesis of human membranous nephropathy. Anti-PLA ₂R antibodies appear to predict activity of the disease as well as response to therapy. Pediatric and adult cases of membranous nephropathy occurring in the presence of circulating cationic bovine serum album (BSA) and anti-BSA antibodies have also been described, raising the possibility that food antigens may be involved in the development of membranous nephropathy. Moreover, the results of genetic susceptibility have become available. Exciting progress has also been made in the treatment of this disease including therapy with adrenocorticotropic hormone and rituximab. Summary: Understanding disease pathogenesis is crucial in guiding patient evaluation and designing appropriate therapy. Recent discoveries have helped to elucidate the pathophysiology of membranous nephropathy and may facilitate a more patient-specific treatment approach in these patients.