title: IgA nephropathy.
abstract: Globally, IgA nephropathy (IgAN) is the most common primary glomerulonephritis that can progress to renal failure. The exact pathogenesis of IgAN is not well defined, but current biochemical and genetic data implicate overproduction of aberrantly glycosylated IgA1. These aberrant immunoglobulins are characterized by galactose deficiency of some hinge-region O-linked glycans. However, aberrant glycosylation alone is insufficient to induce renal injury: the participation of glycan-specific IgA and IgG autoantibodies that recognize the undergalactosylated IgA1 molecule is required. Glomerular deposits of immune complexes containing undergalactosylated IgA1 activate mesangial cells, leading to the local overproduction of cytokines, chemokines and complement. Emerging data indicate that mesangial-derived mediators that are released following mesangial deposition of IgA1 lead to podocyte and tubulointerstitial injury via humoral crosstalk. Patients can present with a range of signs and symptoms, from asymptomatic microscopic haematuria to macroscopic haematuria. The clinical progression varies, with 30-40% of patients reaching end-stage renal disease 20-30 years after the first clinical presentation. Currently, no IgAN-specific therapies are available and patients are managed with the aim of controlling blood pressure and maintaining renal function. However, new therapeutic approaches are being developed, building upon our ever-improving understanding of disease pathogenesis.
authors.affiliation: Nephrology Center, 10/F Li Shu Pui Block, Hong Kong Sanatorium and Hospital, 2 Village Road, Happy Valley, Hong Kong.|Department of Medicine, University of Hong Kong, Hong Kong.
authors.forename: Kar Neng
authors.initials: KN
authors.lastname: Lai
authors.affiliation: Department of Medicine, University of Hong Kong, Hong Kong.
authors.forename: Sydney C W
authors.initials: SC
authors.lastname: Tang
authors.affiliation: Department of Emergency and Organ Transplant, University of Bari, Valenzano, Bari, Italy.
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Schena
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Novak
authors.affiliation: Medical Corporation Showakai, Tokyo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Agnes B
authors.initials: AB
authors.lastname: Fogo
authors.affiliation: Department of Medicine, Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Glassock
mesh_terms: D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005922:Glomerulonephritis, IGA / Q000150:complications* / Q000453:epidemiology / Q000503:physiopathology*; D006417:Hematuria / Q000209:etiology; D006801:Humans; D006973:Hypertension / Q000209:etiology; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood; D007668:Kidney / Q000276:immunology / Q000503:physiopathology; D011507:Proteinuria / Q000209:etiology; D051437:Renal Insufficiency / Q000209:etiology*
chemical_list: D007070:Immunoglobulin A