Description and classification

Membranous nephropathy (MN) is a chronic inflammatory disease of the glomeruli which is characterised by subepithelial in situ deposition of immune complexes at the glomerular basement membrane (see figure). For this reason it is also known as membranous glomerulonephritis (MGN).1,2 The deposition of complexes results in a dysfunctional permeability of the capillary walls of the glomeruli, leading to proteinuria and very frequently to nephrotic syndrome. Besides the highly increased protein secretion in the urine (>3.5 g/24 h), the latter is also characterised by a reduced concentration of protein in the blood (hypoproteinaemia), an increased concentration of blood lipids (hyperlipidaemia) and oedema.3

Immunohistochemistry (IgG1 staining) of renal tissue samples
Left: inflamed renal glomeruli of a patient with primary MN; antibodies in the region of the glomerular basement membrane (red)
Right: healthy renal tissue; no antibody detection. Hoxha et al., Kidney Int. 82, 797-804 (2012)
Immunohistochemistry (IgG1 staining) of renal tissue samples

Around 20-30 % of MN cases are of a secondary form and arise as a result of a different underlying disease or drug therapy.4,5,6  They must be differentiated from primary MN, for which an underlying secondary disease has not been found. In 2009, autoantibodies against phospholipase A2 receptors (anti-PLA2R) were found in around 70 % of primary MN patients.7 Since then it has been possible to differentiate between anti-PLA2R positive and idiopathic cases (without detectable autoantibodies and underlying secondary disease) (see table). This nomenclature, however, is not used in all of the literature and many patients who are positive for anti-PLA2R are misleadingly called idiopathic.5

Causes of membranous nephropathy (MN):
Primary MN
KDIGO: “Kidney Disease: Improving Global Outcome”
  • Anti-PLA2R autoantibodies
  • Idiopathic (without detectable autoantibodies and underlying secondary disease)
Secondary MN (for a complete list see KDIGO6)
  • Infections (e.g. hepatitis B virus, hepatitis C virus, syphilis, malaria)
  • Autoimmune diseases (e.g. rheumatoid arthritis, Sjögren's syndrome, bullous pemphigoid)
  • Carcinoses
  • Other diseases (e.g. sickle cell anaemia, Guillain-Barré syndrome)
  • Induced by medication (e.g. non-steroidal anti-inflammatory drugs (NSAID), gold, mercury, penicillamine)

Since different diagnostic procedures and therapies are applied to the two forms of disease, the differentiation between primary and secondary MN is of major clinical importance.6 While therapy in secondary MN is aimed at the underlying disease, patients with primary MN are mainly treated with  an  immunosuppressive therapy. Correct and fast diagnosis can therefore help to avoid unnecessary medication and extensive diagnostic procedures.