A podocyte view of membranous nephropathy: from Heymann nephritis to the childhood human disease

  • Pierre Ronco
  • Hanna Debiec
Invited Review


Membranous nephropathy (MN) is characterized by an accumulation of immune deposits on the subepithelial side of the glomerular basement membrane, which results in complement activation and proteinuria. Since 2002, several major antigens of the podocyte have been identified in human MN, the first one being neutral endopeptidase (NEP), the alloantigen involved in neonatal cases of MN that occur in newborns from NEP-deficient mothers. This discovery opened the field to the major advances that have occurred since then in the pathophysiology and treatment of MN. It is remarkable that experimental models such as Heymann nephritis and cationic bovine serum albumin-induced MN in the rabbit predicted the pathomechanisms of the human glomerulopathy. The podocyte is at the center of the pathogenesis of MN either by providing a source of endogenous antigens or by creating an environment favorable to deposition and accumulation of immune complexes containing exogenous (non-podocyte) antigens. The podocyte is also a victim of complement activation and antibody blocking activity against enzymes or receptors. A search for innovative drugs aimed at protecting this cell against complement activation and the effects of prolonged ER stress has become a priority.


Membranous nephropathy (MN) Podocyte Neutral endopeptidase (NEP) Cationic bovine serum albumin (cBSA) Complement pathways Regulated intramembrane proteolysis (RIP) 



The research of the authors is supported by grants from the European Research Council (ERC-2012-ADG_20120314; Grant Agreement n° 322947) and the 7th Framework Programme of the European Community, contract 2012-305608 « European Consortium for High-Throughput Research in Rare Kidney Diseases (EURenOmics) ».


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© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Inserm UMR_S 1155Hôpital TenonParisFrance
  2. 2.Sorbonne Universités, UPMC Univ Paris 06ParisFrance
  3. 3.AP-HP, Hôpital Tenon, Service de Néphrologie et DialysesParisFrance

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