IgA nephropathy pathophysiology

Jump to navigation Jump to search

IgA nephropathy Microchapters


Patient Information


Historical Perspective




Differentiating IgA nephropathy from other Diseases

Epidemiology and Demographics

Risk Factors


Natural History, Complications and Prognosis


Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings





Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies


Medical Therapy


Primary prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

IgA nephropathy pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides


American Roentgen Ray Society Images of IgA nephropathy pathophysiology

All Images
Echo & Ultrasound
CT Images

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on IgA nephropathy pathophysiology

CDC on IgA nephropathy pathophysiology

IgA nephropathy pathophysiology in the news

Blogs on IgA nephropathy pathophysiology

Directions to Hospitals Treating IgA nephropathy

Risk calculators and risk factors for IgA nephropathy pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1],Ali Poyan Mehr, M.D. [2]; Associate Editor(s)-in-Chief: Olufunmilola Olubukola M.D.[3]


IgA nephropathy is characterized by the presence of aberrant IgA1 immunoglobulins deposited on the glomerular mesangium. IgG and IgM may also be present to a much lower extent. On the other hand, serum IgA1 levels are elevated in patients with IgA nephropathy in 30-50% of cases. IgA1 subtypes contain galactose-deficient 3-6 O-glycans that may act as binding sites for anti-N-acetyl-galactosamine antibodies. These antibodies have been shown to be expressed following antigenic exposure to certain infectious agents. Currently, IgA nephropathy is believed to be a 4-hit process that eventually leads to IgA deposition on glomerular mesangium. Although mesangial deposition is most commonly seen in patients with IgA nephropathy, other pathological features might still be present.


To understand the pathology behind IgAN, there must be an understanding of the physiology of IgA.


Serum IgA1 levels are increased in 30-50% of patients with IgA nephropathy. The elevated serum levels of IgA1 in such patients is currently believed to be genetically determined. Nonetheless, genetic predisposition and aberrant glycosylation do not seem to sufficiently cause IgA nephropathy alone.


Four-Hit Hypothesis of IgA Nephropathy
(Adapted from Suzuki H, Kiryluk K, Novak J, et al. The pathophysiology of IgA nephropathy. J Am Soc Nephrol. 2011; 22(10):1795-803)

Microscopic Pathology

Light Microscopy Findings

  • Ultimately, IgA nephropathy may have any of the following 6 findings on light microscopy (in increasing order of severity):
    • Normal appearing biopsy
    • Focal mesangial hypercellularity
    • Diffuse mesangial hypercellularity
    • Focal proliferative glomerulonephritis
    • Diffuse proliferative glomerulonephritis
    • Chronic sclerosing glomerulonephritis

Electron Microscopy Findings

  • On electron microscopy, mesangial deposits are most commonly seen. However, depositions on capillary walls are possible; they herald worse prognosis.
  • The following variations may also be found but they are not specific to IgA nephropathy[12]:
    • Segmental endocapillary proliferation
    • egmental Glomerulosclerosis and adhesions
    • Tubular atrophy and interstitial fibrosis
    • Glomerular crescent surrounding the glomerular tuft

Associated Conditions


  1. Donadio JV, Grande JP (2002). "IgA nephropathy". N Engl J Med. 347 (10): 738–48. doi:10.1056/NEJMra020109. PMID 12213946.
  2. Lomax-Smith JD, Zabrowarny LA, Howarth GS, Seymour AE, Woodroffe AJ (1983). "The immunochemical characterization of mesangial IgA deposits". Am J Pathol. 113 (3): 359–64. PMC 1916361. PMID 6359892.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB; et al. (2011). "The pathophysiology of IgA nephropathy". J Am Soc Nephrol. 22 (10): 1795–803. doi:10.1681/ASN.2011050464. PMID 21949093.
  4. Allen AC, Harper SJ, Feehally J (1995). "Galactosylation of N- and O-linked carbohydrate moieties of IgA1 and IgG in IgA nephropathy". Clin Exp Immunol. 100 (3): 470–4. PMC 1534466. PMID 7774058.
  5. Odani H, Yamamoto K, Iwayama S, Iwase H, Takasaki A, Takahashi K; et al. (2010). "Evaluation of the specific structures of IgA1 hinge glycopeptide in 30 IgA nephropathy patients by mass spectrometry". J Nephrol. 23 (1): 70–6. PMID 20091489.
  6. Novak J, Julian BA, Mestecky J, Renfrow MB (2012). "Glycosylation of IgA1 and pathogenesis of IgA nephropathy". Semin Immunopathol. 34 (3): 365–82. doi:10.1007/s00281-012-0306-z. PMID 22434325.
  7. 7.0 7.1 7.2 Tomana M, Novak J, Julian BA, Matousovic K, Konecny K, Mestecky J (1999). "Circulating immune complexes in IgA nephropathy consist of IgA1 with galactose-deficient hinge region and antiglycan antibodies". J Clin Invest. 104 (1): 73–81. doi:10.1172/JCI5535. PMC 408399. PMID 10393701.
  8. Berthoux F, Suzuki H, Thibaudin L, Yanagawa H, Maillard N, Mariat C; et al. (2012). "Autoantibodies targeting galactose-deficient IgA1 associate with progression of IgA nephropathy". J Am Soc Nephrol. 23 (9): 1579–87. doi:10.1681/ASN.2012010053. PMC 3431415. PMID 22904352.
  9. Espinosa M, Ortega R, Gómez-Carrasco JM, López-Rubio F, López-Andreu M, López-Oliva MO; et al. (2009). "Mesangial C4d deposition: a new prognostic factor in IgA nephropathy". Nephrol Dial Transplant. 24 (3): 886–91. doi:10.1093/ndt/gfn563. PMID 18842673.
  10. Roos A, Rastaldi MP, Calvaresi N, Oortwijn BD, Schlagwein N, van Gijlswijk-Janssen DJ; et al. (2006). "Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease". J Am Soc Nephrol. 17 (6): 1724–34. doi:10.1681/ASN.2005090923. PMID 16687629.
  11. Miyamoto H, Yoshioka K, Takemura T, Akano N, Maki S (1988). "Immunohistochemical study of the membrane attack complex of complement in IgA nephropathy". Virchows Arch A Pathol Anat Histopathol. 413 (1): 77–86. PMID 3131958.
  12. Wyatt RJ, Julian BA (2013). "IgA nephropathy". N Engl J Med. 368 (25): 2402–14. doi:10.1056/NEJMra1206793. PMID 23782179.
  13. 13.0 13.1 13.2 13.3 13.4 13.5 13.6 13.7 Radhakrishnan J, Cattran DC (2012). "The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines--application to the individual patient". Kidney Int. 82 (8): 840–56. doi:10.1038/ki.2012.280. PMID 22895519.

Template:WH Template:WS