The pathophysiology of IgA nephropathy

J Am Soc Nephrol. 2011 Oct;22(10):1795-803. doi: 10.1681/ASN.2011050464. Epub 2011 Sep 23.


Here we discuss recent advances in understanding the biochemical, immunologic, and genetic pathogenesis of IgA nephropathy, the most common primary glomerulonephritis. Current data indicate that at least four processes contribute to development of IgA nephropathy. Patients with IgA nephropathy often have a genetically determined increase in circulating levels of IgA1 with galactose-deficient O-glycans in the hinge-region (Hit 1). This glycosylation aberrancy is, however, not sufficient to induce renal injury. Synthesis and binding of antibodies directed against galactose-deficient IgA1 are required for formation of immune complexes that accumulate in the glomerular mesangium (Hits 2 and 3). These immune complexes activate mesangial cells, inducing proliferation and secretion of extracellular matrix, cytokines, and chemokines, which result in renal injury (Hit 4). Recent genome-wide association studies identify five distinct susceptibility loci--in the MHC on chromosome 6p21, the complement factor H locus on chromosome 1q32, and in a cluster of genes on chromosome 22q22--that potentially influence these processes and contain candidate mediators of disease. The significant variation in prevalence of risk alleles among different populations may also explain some of the sizable geographic variation in disease prevalence. Elucidation of the pathogenesis of IgA nephropathy provides an opportunity to develop disease-specific therapies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers / blood
  • Biomarkers / urine
  • Galactose / metabolism
  • Glomerulonephritis, IGA / etiology*
  • Glomerulonephritis, IGA / genetics
  • Glomerulonephritis, IGA / metabolism
  • Glomerulonephritis, IGA / physiopathology
  • Glycosylation
  • Humans
  • Immunoglobulin A / immunology
  • Immunoglobulin A / metabolism*
  • Mesangial Cells / metabolism


  • Biomarkers
  • Immunoglobulin A
  • Galactose