New insights into the pathogenesis of IgA nephropathy.
IgA nephropathy (IgAN) is the most common diagnosis amongst primary glomerular diseases in most countries where renal biopsies are regularly performed. Only a fraction of these patients is at high risk of losing glomerular filtration rate (GFR) in particular those with high grade proteinuria, uncontrolled hypertension or already impaired GFR at diagnosis, and those with renal scars in the renal biopsy. Genetic modifiers of IgAN onset and/or course are emerging. Spontaneous animal models of IgAN are problematic given considerable species differences between the rodent and human IgA system. However, new transgenic models help to better understand the pathogenesis. A key pathogenetic role appears to be played by underglycated IgA1 as well as autoantibodies to these IgA glycoforms and IgA receptors such as CD89 and transferrin receptor 1. Once IgA and/or IgA-containing immune complexes are deposited or formed in the mesangium, secondary effector mechanisms become important including complement activation, release of mesangial growth factors (in particular platelet-derived growth factor), and finally non-IgAN-specific events that culminate in glomerular and subsequently renal tubulointerstitial scaring. Here, we review these processes and describe potential novel therapeutic targets in IgAN.
Division of Nephrology, RWTH University Hospital Aachen, 52057, Aachen, Germany, jfloege@ukaachen.de.
Jürgen
J
Floege
Ivan C
IC
Moura
Mohamed R
MR
Daha
D015703:Antigens, CD / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D005919:Glomerular Filtration Rate / Q000276:immunology; D005922:Glomerulonephritis, IGA / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007668:Kidney / Q000276:immunology* / Q000473:pathology*; D010982:Platelet-Derived Growth Factor / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology; D011990:Receptors, Transferrin / Q000276:immunology
D015703:Antigens, CD; C068126:CD71 antigen; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D010982:Platelet-Derived Growth Factor; D011961:Receptors, Fc; D011990:Receptors, Transferrin; D003165:Complement System Proteins