title: [IgA Nephropathy. Facts, uncertainties, and potential causal therapy approaches].
abstract: IgA nephropathy is currently the most frequently investigated glomerulonephritis. The disease is defined by the presence of dominant or co-dominant deposits of IgA1 in the glomerular mesangium. Circulating immune complexes are most likely the source of the deposited IgA1. However, it is also possible that the aggregates of structurally altered IgA1 or enhanced binding to IgA receptors expressed on mesangial cells lead to deposition. The cause of the formation of immune complexes responsible for IgA nephropathy lies in the incomplete O-linked oligosaccharide side chains, which, due to the deficiency of corresponding glycosyltransferases, lack terminal galactose residues leading to the exposure of N-acetylgalactosamine. Naturally occurring antibodies of the IgG or IgA1 isotype bind to this sugar antigen. In the clinical course, we differentiate between the early stage usually characterized by hematuria, and a variable late stage characterized either by a clinical remission, by persistence of hematuria, or by increasing proteinuria and blood pressure and decreasing renal function in one third of the patients. In the early stage, it is difficult to predict the prognosis of IgA nephropathy, either on the basis of clinical presentation and morphological findings, or according to the level of galactose-deficient IgA1 in the circulation. The reliable criteria of serious prognosis emerge only in the later stages of the disease and include proteinuria, hypertension, and histologically apparent tubular atrophy and interstitial sclerosis. The dominant trend in the treatment of IgA nephropathy is the emphasis on administration of ACE inhibitors/sartans, which are introduced into the treatment at the time of microalbuminuria. If proteinuria does not decrease below 1 g/24 h, treatment with prednisone is justifiable. New findings concerning the molecular/cellular mechanism involved in the pathogenesis of IgA nephropathy suggest the possible therapeutical interference with the generation of nephritogenic immune complexes by a selective blocking of the IgA1 molecules with altered glycan structures using monovalent reagents.
authors.forename: Karel
authors.initials: K
authors.lastname: Matoušovic
authors.forename: Jiří
authors.initials: J
authors.lastname: Městecký
authors.forename: Karel
authors.initials: K
authors.lastname: Vondrák
authors.forename: Jiří
authors.initials: J
authors.lastname: Dušek
authors.forename: Eliška
authors.initials: E
authors.lastname: Chvátalová
authors.forename: Jaromír
authors.initials: J
authors.lastname: Háček
authors.forename: Milada
authors.initials: M
authors.lastname: Horynová
authors.forename: Alena
authors.initials: A
authors.lastname: Kašperová
authors.forename: Pavel
authors.initials: P
authors.lastname: Rossmann
authors.forename: Ivan
authors.initials: I
authors.lastname: Šterzl
authors.forename: Milan
authors.initials: M
authors.lastname: Raška
mesh_terms: D019468:Disease Management; D005922:Glomerulonephritis, IGA / Q000628:therapy*; D006801:Humans
keywords: IgA nephropathy - immunoglobulin A - O-glycosylation - immune complexes - therapy.