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IgA NEPHROPATHY MOD VIDEO

There may be a hidden culprit in IgA Nephropathy: the gut

IgA Nephropathy is thought to primarily originate in the ileum.1

See the role the gut plays in IgA Nephropathy

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~33%

of patients with IgA Nephropathy will experience recurrence of the disease after kidney transplantation, indicating that the source of disease is extrarenal in origin.14,15

IgA NEPHROPATHY MECHANISM OF DISEASE

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IgA Nephropathy, or IgAN, is an autoimmune disease that affects the kidneys, but may begin in the gut. The Gut-Kidney-Axis may play a defining role in IgAN.1,16

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Mucosal IgA1 has a poorly-galactosylated hinge region, and is often secreted as a dimer.1,17

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Gut associated lymphoid tissue (GALT) contains specialised lymphoid tissues, including Peyer's patches, which are concentrated in the distal ileum. These provide immune surveillance, including producing mucosal type IgA1.1,18

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Systemic IgA and IgG autoantibodies react to the galactose-deficient mucosal IgA1 hinge region, forming immune complexes.17,19

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The circulating complexes deposit in the kidney glomerular mesangium, where they become trapped and mucosal IgA binds to extracellular matric components.17,20

This autoimmune response leads to glomerular and tubulo-interstitial injury, resulting in proteinuria and a progressive decline in renal function.21

See the impact of the gut-kidney axis in IgAN

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IgA=immunoglobulin A; IgAN=immunoglobulin A Nephropathy; MOD=mechanism of disease.

References: 1. Barratt J, Rovin BH, Cattran D, et al. Kidney Int Rep. 2020;5(20):1620-1624. doi:10.1016/j.ekir.2020.08.009

2. Hastings MC, Bursac Z, Julian BA, et al. Kidney Int Rep. 2017;3(1):99-104. doi:10.1016/j.ekir.2017.08.008

3. Schena FP. Am J Med. 1990;89(2):209-215. doi:10.1016/0002-9343(90)90300-3

4. Barratt J, Feehally J. Semin Nephrol. 2011;31(4):349-360. doi:10.1016/j.semnephrol.2011.06.006

5. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int. 2012;2(suppl 2):259-274.

6. IgA Nephropathy Foundation of America, Inc. The Voice of the Patient: Externally Led Patient-Focused Drug Development Meeting on IgA Nephropathy. https://nkf.egnyte.com/dl/aHGCS6tPNM/?. Accessed August 18, 2021.

7. Penfold RS, Prendecki M, McAdoo S, Tam FWK. Int J Nephrol Renovasc Dis. 2018;11:137-148. doi:10.2147/IJNRD.S129227

8. Arroyo AH, Bomback AS, Butler B, et al. Clin Nephrol. 2015;84(3):145-155. doi:10.5414/CN108556

9. Rauen T, Wied S, Fitzner C, et al; for the STOP-IgAN Investigators. Kidney Int Supp. 2020;98(4):1044-1052. doi:10.1016/j.kint.2020.04.046

10. Lafayette RA, Kelepouris E. Am J Nephrol. 2018;47(suppl 1):43-52. doi:10.1159/000481636

11. United States Renal Data System (USRDS). 2018 USRDS Annual Data Report. Vol 2. 2018; chap 9. Accessed April 7, 2021. https://usrds.org/media/1734/v2_c09_esrd_costs_18_usrds.pdf.

12. Golestaneh L, Alvarez PJ, Reaven N, et al. Am J Manag Care. 2017;23(10 Suppl):S163-S172.

13. Knoop T, Vikse BE, Svarstad E, Leh S, Reisæter AV, Bjørneklett R. Am J Kidney Dis. 2013;62(5):883-890. doi:10.1053/j.ajkd.2013.04.019

14. Ponticelli C, Glassock RJ. Clin J Am Soc Nephrol. 2010;5(12):2363-2372. doi:10.2215/CJN.06720810

15. Ponticelli C, Traversi L, Banfi G. Pediatr Transplant. 2004:8(4):334-338. doi:10.1111/j.1399-3046.2004.00177.x

16. Kiryluk K, Novak J. J Clin Invest. 2014;124(6):2325-2332. doi:10.1172/JCI74475

17. Yeo SC, Cheung CK, Barratt J. Pediatr Nephrol. 2018;33(5):763-777. doi:10.1007/s00467-017-3699-z

18. Jung C, Hugot JP, Barreau F. Int J Inflam. Published online September 19, 2010. doi:10.4061/2010/823710

19. Barratt J, Smith AC, Feehally J. Nephrology (Carlton). 2007;12(3):275-284. doi:10.1111/j.1440-1797.2007.00797.x

20. Boyd JK, Cheung CK, Molyneux K, Feehally J, Barratt J. Kidney Int. 2012;81(9):833-843. doi:10.1038/ki.2011.501

21. Lafayette RA. Transl Res. 2014;163(1):3-7. doi:10.1016/j.trasl.2013.08.007

22. Thompson A, Carroll K, Inker LA, et al. Clin J Am Soc Nephrol. 2019;14(3):469-481. doi:10.2215/CJN.08600718

23. Ibrahim A, Garg AX, Knoll GA, Akbari A, White CA. Am J Transplant. 2013;13(3):708-713. doi:10.1111/ajt.12050

24. Levey AS, Gansevoort RT, Coresh J, et al. Am J Kidney Dis. 2020;75(1):84-104. doi:10.1053/j.ajkd.2019.06.009

25. Goto M, Wakai K, Kawamura T, Ando M, Endoh M, Tomino Y. Nephrol Dial Transplant. 2009;24(10):3068-3074. doi:10.1093/ndt/gfp273

26. Brantsma AH, Atthobari J, Bakker SJ, de Zeeuw D, de Jong PE, Gansevoort RT. J Am Soc Nephrol. 2007;18(2):637-645. doi:10.1681/ASN.2006070738