IgA nephropathy risk factors

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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]

Overview

Several risk factors have been found to be associated with IgA nephropathy, most of which seem to be associated with disease outcome and progression into ESRD rather than disease development. Male gender, native Americans and American and European populations around the pacific rim and asian populations such as China and Japan are more commonly diagnosed with IgA nephropathy.

Risk Factors

Several risk factors have been found to be associated with IgA nephropathy, most of which seem to be associated with disease outcome and progression into ESRD rather than disease development.

Broadly, the only risk factors that seem to be associated with the development of IgA nephropathy are:

Gender:

  • Male predominance was found to be associated in some studies, especially in Northern America with a 2:1 male to female ratio.[1][2]

Ethnicity:

  • Native Americans and American and European populations around the Pacific Rim and Asian populations such as China and Japan are more commonly diagnosed with IgA nephropathy.[3]
  • Blacks have a much less rate of diagnosis.[4]

Family History:

  • Up to 40% of immediate family members have elevated levels of aberrant IgA1 levels and approximately 5% of relatives will manifest IgA nephropathy.[5][3]
  • The genetic susceptibility plays the most and perhaps the only important role in the development of IgA nephropathy.
  • The role of genetics has been well established in the pathogenesis of IgA nephropathy.
    • The most common mode of inheritance is autosomal-dominant pattern with incomplete penetrance.[6]
    • There is an emerging observation that galactose-deficient IgA1 immunoglobulin formation is in fact a genetic trait in specific populations, ethnicities, and geographical locations such as Pacific Rim and Asia.[3]
    • It is much less frequently observed in African populations.[4]
  • Further evidence from studies that evaluate the diagnosis of IgA nephropathy in relatives reveals that not only 90% of patients with IgA nephropathy have high circulating levels of IgA1.
  • 30-40% of relatives of patients with IgA nephropathy have elevated levels of IgA1.
    • Observational studies show that relatives of IgA nephropathy almost never have clinical forms of IgA nephropathy or renal injury except in 5% of the cases[5][3], which suggests environmental influences and further emphasizes the multi-hit pathogenesis.[7][5]
  • IgA nephropathy does not seem to be inherited by simple Mendelian genetics.
  • Major histocompatibility complex (MHC) DQ is likely to be involved, according to a study on patients with white European ancestry.
  • Furthermore, studies enrolling Chinese, African, and European patients showed involvement of the same loci even among patients of different ethnicities.[8]

A total of 5 loci are significant in IgA nephropathy:

  • 3 loci on 6p21 encoding components of MHC I and MHC II response

References

  1. Wyatt RJ, Kritchevsky SB, Woodford SY, Miller PM, Roy S, Holland NH; et al. (1995). "IgA nephropathy: long-term prognosis for pediatric patients". J Pediatr. 127 (6): 913–9. PMID 8523188.
  2. Wyatt RJ, Julian BA, Baehler RW, Stafford CC, McMorrow RG, Ferguson T; et al. (1998). "Epidemiology of IgA nephropathy in central and eastern Kentucky for the period 1975 through 1994. Central Kentucky Region of the Southeastern United States IgA Nephropathy DATABANK Project". J Am Soc Nephrol. 9 (5): 853–8. PMID 9596083.
  3. 3.0 3.1 3.2 3.3 Kiryluk K, Julian BA, Wyatt RJ, Scolari F, Zhang H, Novak J; et al. (2010). "Genetic studies of IgA nephropathy: past, present, and future". Pediatr Nephrol. 25 (11): 2257–68. doi:10.1007/s00467-010-1500-7. PMC 2937145. PMID 20386929.
  4. 4.0 4.1 Hall YN, Fuentes EF, Chertow GM, Olson JL (2004). "Race/ethnicity and disease severity in IgA nephropathy". BMC Nephrol. 5: 10. doi:10.1186/1471-2369-5-10. PMC 517500. PMID 15341669.
  5. 5.0 5.1 5.2 5.3 Radford MG, Donadio JV, Bergstralh EJ, Grande JP (1997). "Predicting renal outcome in IgA nephropathy". J Am Soc Nephrol. 8 (2): 199–207. PMID 9048338.
  6. Wyatt RJ, Julian BA (2013). "IgA nephropathy". N Engl J Med. 368 (25): 2402–14. doi:10.1056/NEJMra1206793. PMID 23782179.
  7. Lin X, Ding J, Zhu L, Shi S, Jiang L, Zhao M; et al. (2009). "Aberrant galactosylation of IgA1 is involved in the genetic susceptibility of Chinese patients with IgA nephropathy". Nephrol Dial Transplant. 24 (11): 3372–5. doi:10.1093/ndt/gfp294. PMID 19531670.
  8. Kiryluk K, Li Y, Sanna-Cherchi S, Rohanizadegan M, Suzuki H, Eitner F; et al. (2012). "Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis". PLoS Genet. 8 (6): e1002765. doi:10.1371/journal.pgen.1002765. PMC 3380840. PMID 22737082.

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