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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

peyers patches iga nephropathy if we cannot do

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